Below are the previous Clinical Trials Reports that we have posted on our website.
|Plaque Psoriasis, Psoriatic Arthritis, Crohn’s Disease and Ulcerative Colitis
|This Phase I clinical trial of single-dose, double-blind, randomised, three-arm study design is being conducted across multiple Australian sites in over 200 healthy volunteers. The primary objective is to demonstrate equivalent pharmacokinetics (PK) of NeuLara to US- and EU-sourced Stelara®.
|The secondary objective of this study is to demonstrate equivalent safety of NeuLara to US- and EU-sourced Stelara®. In preclinical investigations, NeuLara has been extensively tested to confirm structural and functional similarity in comparison to the reference product Stelara®. These investigations included positive PK and safety results from a non-clinical primate study, as well as physicochemical analyses of Stelara® and NeuLara. NeuLara is under clinical development as a biosimilar candidate of Ustekinumab, an antibody targeting interleukin-12 and -23, approved under the brand name Stelara® to treat patients with plaque psoriasis, psoriatic arthritis, Crohn’s disease and ulcerative colitis.
|Alder BioPharmaceuticals, Inc.
|This Phase I clinical trial of double-blind, placebo-controlled study design will recruit approximately 100 healthy men and women between the ages of 18 and 55 and will evaluate the safety, tolerability and pharmacokinetic profile of ALD1910 at various doses.
|ALD1910 is an investigational monoclonal antibody (mAb) representing a potential new therapeutic mode of action, focusing on a new pathway in migraine prevention, different to the usual mechanism of inhibiting the calcitonin gene-related peptide (CGRP), a neuropeptide believed to mediate and initiate migraine attacks. In lieu, ALD1910 in preclinical studies was shown to inhibit pituitary adenylate cyclase-activating polypeptide (PACAP), an important signaling molecule in the pathophysiology of migraine.
|Amphivena Therapeutics, Inc.
|Earlier this month, 15th October, the sponsor announced that over 50 patients have received AMV564 in two Phase I clinical trials
for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). AMV564, a bivalent, bispecific (2:2) T cell engager that binds CD33 and CD3, is currently being evaluated in a Phase I clinical trial in patients with relapsed/refractory AML at five different medical research centres in the U.S..
|The sponsor states that AMV564 has shown novel clinical activity by rapidly and selectively eliminating leukaemic blasts and rare immature, granulocytic and monocytic MDSCs while leaving normal CD33-expressing cells in tact, including neutrophils and monocytes. AMV564 is also being assessed in a Phase I solid tumour study which is currently open to recruitment.
|Relapsed or Refractory Non-Hodgkin Lymphoma (NHL) or Multiple Myeloma (MM)
|This Phase I clinical trial is of an open-label, dose escalation and dose expansion study design in patients with selected haematological malignancies (relapsed or refractory NHL or MM). The dose escalation phase of the study will assess the safety and tolerability of NKTR-255 as monotherapy in roughly 40 patients in order to ascertain a recommended Phase II dose (RP2D) for NKTR-255. The dose expansion phase of the study will recruit in two separate cohorts: the first cohort will recruit patients with MM or NHL (relapsed salvage) to evaluate the NKTR-255 RP2D as a monotherapy and the second cohort will recruit patients with MM or NHL (relapsed/refractory salvage) to evaluate the NKTR-255 RP2D in combination with targeted antibodies, including anti-CD38 monoclonal antibody, Daratumumab.
|As secondary study objectives, the trial will also assess pharmacokinetic and pharmacodynamic effects, anti-tumour activity and biomarker assessments. NKTR-255 is an IL-15 receptor agonist designed to trigger the IL-15 pathway and expand NK cells and promote the survival and proliferation of memory CD8+ T cells without inducing suppressive regulatory T cells. Through optimal engagement of the IL-15Rα/IL-2Rβγ receptor complex, NKTR-255 enhances formation of long-term immunological memory, which may impact on a sustained anti-tumour immune response. NKTR-255 is uniquely designed to overcome the challenges of recombinant IL-15, which undergoes rapid systemic clearance and therefore is required to be administered frequently and in high doses, limiting its utility due to toxicity and inconvenience of administration.
|Traumatic Brain Injury (TBI) and Hypoxic-Ischemic Encephalopathy (HIE).
|This Phase I/II clinical trial is of a single arm, non-randomized study design that is anticipated to recruit 24 subjects. The primary objective of the study is to determine the safety and treatment effect of HB-adMSCs for treatment of sub-acute and chronic TBI and HIE. HB-adMSCs are administered via three intravenous infusions over a six-week period and follow-up assessments at six months and one-year post-infusion. HB-adMSCs are autologous and have an established safety profile.
|Presently there are no therapies that have demonstrated clinical benefit in chronic TBI. Chronic neuroinflammation has been demonstrated after neurological injury for up to 13 years in patients after TBI and is associated with progressive white matter loss. HB-adMSCs are expected to provide immunomodulation to reduce chronic microglial activation as measured by [11C]ER-176 uptake value measurements systemically and in the thalamus. Overall results are anticipated to be a decrease in neuronal cell loss and improvements in neurocognitive outcomes (improvements in verbal response, motor function, and memory, that correlate to physical changes in the brain).
|DiaMedica Therapeutics Inc.
|Chronic Kidney Disease (CKD)
|This Phase II clinical trial is of a multi-centre, open-label study design of roughly 60 patients with CKD, who will all be recruited in the U.S. to two cohorts across 10 clinical sites. The two cohorts of the study will be patients with CKD caused by IgAN and non-diabetic, hypertensive African American patients with CKD. African Americans are at higher risk for CKD than Caucasians, and African Americans who have the mutated APOL1 gene are at an even more greater risk. The study is designed to capture APOL1 gene mutation as an exploratory biomarker. The study will evaluate two dose levels of DM199 within each cohort. Enrolled patients will receive DM199 by subcutaneous injection twice weekly for 95 days . The primary endpoints of the study include safety, tolerability, blood pressure and kidney function, which will be evaluated by changes from base line in eGFR and albuminuria, as measured by the urinary albumin to creatinine ratio (UACR).
|DM199 is a synthetic recombinant equivalent of the human serine protease kallikrein (KLK1). The KLK1 protein plays a key function in the regulation of various physiological processes in the kidneys, including blood flow, inflammation, fibrosis and oxidative stress. The sponsor proposes that DM199 restores KLK1 levels, enabling the natural physiologic process of the body to selectively release bradykinin-mediated nitric oxide, prostaglandins (PGE2 and PGI2-cAMP) and other anti-inflammatory mediators in the kidneys, which consequently work synergistically to improve renal blood flow (dilating both afferent & efferent arterioles) thus slowing down inflammation, oxidative stress and fibrosis. The sponsor also claims that DM199 possibly is involved in restoring the body’s natural ability to regulate the function of the epithelial sodium channel (ENaC), thus keeping systemic sodium levels in check.
|PB2452 with low-dose Aspirin
|Reversal of Blood Thinning (Antiplatelet Activity)
|This Phase IIb clinical trial is of a multi-centre, randomized, double-blind, placebo-controlled study design to assess the safety and efficacy of PB2452 in reversing the antiplatelet effects of Ticagrelor as part of a dual antiplatelet regimen including low-dose aspirin. Also, this Phase IIb study signifies the beginning of the FDA's aligned registrational trials to support the submission of a Biologics License Application (“BLA”) for a possible accelerated approval of PB2452. Roughly a 200 older and elderly cohort (ages 50 to 80) of patients are anticipated to be recruited, resembling the patient population most likely to be treated with Ticagrelor and potentially benefit from PB2452, if registration is granted. Patients will be randomized in a ratio of 3:1 and will receive either PB2452 or placebo, with roughly 150 participants receiving PB2452. The primary endpoint of the trial is reversal of the antiplatelet effects of Ticagrelor with intravenous infusion of PB2452 or placebo, as measured by a proprietary VerifyNow® PRUTest® biomarker.
|PB2452 is a novel, recombinant, human monoclonal antibody antigen-binding fragment with an intended efficacy to reverse the antiplatelet activity of Ticagrelor in major bleeding and urgent surgery situations. Ticagrelor is an antagonist of the P2Y₁₂ receptor, licensed by Astra Zeneca. In a Phase I clinical trial, PB2452 showed potential to derive life-saving therapeutic benefit through immediate and sustained reversal of Ticagrelor’s antiplatelet activity, mitigating concerns pertaining to bleeding risks associated with the use of antiplatelet medicines. At present there are no approved reversal agents for Ticagrelor treatment or any other antiplatelet therapies.
|Can-Fite BioPharma Ltd.
|Nonalcoholic Steatohepatitis (NASH)/Nonalcoholic Fatty Liver Disease (NAFLD)
|This Phase II clinical trial is of a multicentre, randomized, double-blinded, placebo-controlled, dose-finding efficacy and safety study design recruiting 60 patients with NAFLD with or without NASH. Patients who suffer from NAFLD/NASH with evidence of active inflammation are dosed twice daily with 12.5 mg or 25 mg of oral Namodenoson, or placebo for 12 weeks. The study primary endpoint is the anti-inflammatory effect of the drug, as determined by mean percent change from baseline in ALT (alanine aminotransferase) blood levels and safety. The study secondary endpoint will be the percentage change from baseline of liver fat, as measured by MRI-PDFF (proton density fat fraction).
|Namodenoson is a small orally bioavailable drug that binds selectively with high affinity to the A3 adenosine receptor (A3AR). Namodenoson is being assessed as a second line therapy for hepatocellular carcinoma, with a recently completed Phase II trial and planned Phase III trial for the same clinical indication. A3AR is found highly expressed in diseased cells whereas low expression exists in normal cells. This differential effect is the rationale for such a superior safety profile of the candidate medicine.
|Denovo Bipharma LLC
|Glioblastoma also known as Glioblastoma Multiforme (GBM) in combination with radiation therapy and Temozolomide
|On 15 October of this month, the sponsor announced FDA's approval to initiate Denovo's Phase IIb clinical study of DB102 in patients with newly-diagnosed GBM in combination with radiation and Temozolomide, an alkylating chemotherapy agent used as a first-line treatment for GBM.
|This clinical trial represents an extension of the work to identify a genetically-enriched patient population with diffuse large B-cell lymphoma (DLBCL) who could possibly benefit from DB102 treatment. Upon the sponsor acquiring the licensing rights of DB102 from Eli Lilly & Co., it discovered a novel genetic biomarker, DGM1, that is a potentially predictive biomarker for DB102 response in patients with DLBCL. As DGM1 is a germline biomarker, the sponsor reports also that DGM1 predicts a survival benefit in patients with GBM treated with DB102 plus Temozolomide. This clinical trial is anticipated to recruit 200 newly-diagnosed GBM patients.
|Cystic Fibrosis (CF)
|Earlier this month, 16 October, the sponsor announced the first patient has been recruited in its Phase II clinical trial BALANCE-CFTM 1 to evaluate a new potential treatment for CF. The study will evaluate how different doses of its candidate drug BI 1265162, an inhaled epithelial sodium channel (ENaC) inhibitor, impacts lung function compared to placebo when added to the standard of care in adults and adolescents with CF.
|The ENaC inhibitor is intended as a therapy for patients of all types of CF mutations. It is administrated via the Respimat® inhaler, which is the proprietary platform inhaler of Boehringer Ingelheim. The Respimat® inhaler actively delivers medicine in a slow-moving soft mist that is easy to inhale even for people who have difficulty breathing. People with cystic fibrosis often have a high treatment burden, sometimes spending hours administrating multiple treatments.The rapid inhalation of BI 1265162 ENaC inhibitor via Respimat® that can be administered anywhere is intended to be added to the standard of care.
|Insomnia Associated with Alcohol Cessation (IAAC)
|This Phase II clinical trial of randomized, double-blind, placebo-controlled, multi-centre, parallel-group study design will evaluate the compound’s safety, efficacy, and tolerability in adults with moderate or severe alcohol use disorder who are experiencing IAAC. Participants will receive IMB-115 (1 mg or 2 mg) or placebo, administered orally at bedtime for three weeks. The primary outcome of the study is to evaluate change from baseline of wakefulness after sleep onset (WASO), as measured by polysomnography (PSG). Secondary outcome measures of the study include changes from baseline related to sleep efficiency, latency, total sleep time, and number of awakenings.
|IMB-115 is a novel compound discovered by the sponsor with a novel mechanism of action undergoing clinical development for the treatment of insomnia disorders, including IAAC. Insomnia associated with alcohol cessation is a major challenge for certain patients recovering from alcohol use disorder in their plight to sustain abstinence from alcohol use and currently there are no FDA-approved pharmacological treatment options to help these patients address this challenge.
|Alcohol Use Disorder (AUD)
|This Phase II clinical trial is of a three-arm, double-blind, randomized, placebo-controlled, parallel group, three-site study design to evaluate the effects of ANS-6637 as compared with placebo on responses to in vivo alcohol cue exposure in the human laboratory setting. The study will recruit 81 patients seeking treatment who meet DSM-5 criteria for at least moderate alcohol use disorder. Endpoints include laboratory paradigm alcohol cue-elicited alcohol craving, percentage of subjects with no heavy drinking days, percentage of subjects abstinent from alcohol, and safety.
|ANS-6637 is a selective and reversible aldehyde dehydrogenase 2 (ALDH2) inhibitor, a novel chemical entity with a first-in-class mechanism of action for treating substance use disorder. Based on its mechanism of action in the brain to prevent pathophysiologic dopamine surge without changes to basal dopamine, the sponsor states that ANS-6637 has the potential to prevent drug seeking behaviour, craving and relapse. The sponsor has acquired the licensing rights to ANS-6637 as a spin-out from Gilead Sciences.
|This pivotal Phase III clinical trial will assess the safety and immunogenicity of NanoFlu using the sponsor’s proprietary Matrix-M adjuvant in adult patients aged 65 years and above compared to the quadrivalent influenza vaccine licensed in the U.S.. The study's primary objective is to demonstrate non-inferior immunogenicity as measured by haemagglutination inhibition (HAI) titres of vaccine homologous influenza strains compared to seasonal marketed influenza vaccine.
|Earlier this year in January, the sponsor announced top-line data from a phase II study on NanoFlu. Results from the same clinical trial showed that NanoFlu improved immune responses in adults aged 65 years or older compared to Sanofi’s leading influenza vaccine Fluzone High-Dose.
|Colorectal Cancer (CRC)
|This randomized Phase III study, has been designed following discussions with the FDA and other regulators and is anticipated to recruit 300 CRC patients in ten clinical centres across Europe and the U.S.. The trial will evaluate the safety and clinical benefit of using fluorescence-guided surgery (FGS) with SGM-101 as an intraoperative imaging agent to better identify cancer lesions during the surgical procedure. Participants are administered with 10mg of SGM-101 by injection four days before the scheduled CRC surgical procedure.
|SGM-101 is a tumour-specific antibody conjugated to a fluorophoric dye component that fluoresces under near-infra-red light; it selectively targets a marker on the surface of cancerous cells known as carcinoembryonic antigen (CEA), which is overexpressed by more than 95% of colorectal cancer cells. SGM-101 is being developed to provide oncology surgeons with a novel intraoperative imaging tool designed to improve the visualization of tumour tissues overexpressing CEA in real-time during surgery. The study objective is to demonstrate that SGM-101 could be implemented to enable surgeons to more clearly delineate the margin between cancerous and healthy tissue. This clinical trial is also investigating if SGM-101 use could minimize or circumvent removal of healthy tissue adjacent to tumour cells in order to improve functional outcomes.
Week 7 Oct 2019 – 11 Oct 2019
|Chronic Ischaemic Stroke
|This Phase II clinical trial of double-blind, placebo-controlled study design has recruited 22 subjects that were randomized to one of two groups: a treatment group administered intracerebrally 72 million human neural stem cells or a sham surgery group. Inclusion criteria for the study is for patients to have sustained chronic motor deficits due to an ischemic stroke 4-24 months prior to enrollment, and will be assessed for measures of efficacy for 12 months after surgery and measures of safety for an additional 48 months.
|NSI-566 is a human spinal cord-derived neural stem cell line originating from the spinal cord of an eight-week-old aborted foetus. By intracerebral injection, these foetal stem cells are thought to differentiate into mature neurons usually found in adult human. Consequently they surround and support the impaired motor neurons by integrating into the neural network and forming connections (synapses) with the patient’s neurons. They also ellicit neurotrophic factors or proteins that promote the growth and survival of motor neurons. As well as being clinically investigated for treatment of paralysis in chronic ischaemic stroke subjects, NSI-566 is undergoing clinical development for treatment of paralysis in amyotrophic lateral sclerosis and chronic spinal cord injury.
|Severe Oral Mucositis (SOM)
|This Phase II clinical trial is of a double-blind, placebo-controlled, two-arm, multi-centre study design, in which roughly 200 subjects will be randomized in a 1:1 ratio to receive either AG013 or placebo three times daily following meals, beginning on the first day of chemoradiation therapy and continuing through the course of cancer treatment. The study objective of this clinical trial, is to assess the efficacy (based on the end point of preventing the occurrence and shortening the duration of SOM), safety, and tolerability of a topically administered rinse of AG013 compared to a placebo for reducing the incidence and severity of SOM in patients undergoing traditional chemoradiation for the treatment of head and neck malignant tumours.
|Last month, on 30 September, the sponsor announced initial data from this ongoing Phase II clinical trial of AG013 presented in a poster session at the European Society for Medical Oncology (ESMO) Congress 2019 in Barcelona, Spain. The results highlighted for 42 of the 71 recruited and randomized patients across 48 study sites demonstrated that in the blinded, combined placebo and active treatment groups, there was sufficient evidence of efficacy and safety to continue the study. AG013 is an ActoBiotics® therapeutic candidate formulated to deliver the therapeutic molecule Trefoil Factor 1 to the mucosal tissues in the oral cavity in an oral rinsing solution. Trefoil Factors are a class of peptides involved in the protection of gastrointestinal tissues against mucosal damage and play an important role in subsequent repair. The compound was designed by the sponsor’s strategic partner, ActoBio Therapeutics, Inc.
|This is a Phase II baseline/on-treatment clinical trial investigating the utility of ImaginAb's CD8 tracer, 89Zr-Df-IAB22M2C, to image CD8 T cells before (baseline) and after (on-treatment) cancer patients undergoing immunotherapy-based treatment.
|89Zr-Df-IAB22M2C is a first in class imaging agent that visualizes the immune system using non-invasive, whole-body in vivo PET imaging of CD8 T cells. Using its 'Minibody' platform, the sponsor's technology targets and visualizes CD8+ T-cells to provide highly-specific, quantitative assessment of the immunological status of each cancer lesion within a patient, enabling treatment to be tailored quickly and specifically to the needs of that patient.
|Relapsed/Refractory Multiple Myeloma (RRMM)
|In this ongoing pivotal Phase II HORIZON clinical trial for which the sponsor presented interim results earlier last month at the Society of Hematologic Oncology (SOHO) 2019 Annual Meeting in Houston, TX, USA, Melflufen demonstrated activity in patients with RRMM, many of whom also have extramedullary disease. In this clinical study, patients demonstrated an overall response rate (ORR) of 28% and a clinical benefit rate (CBR) of 40%. 86% of the patients investigated achieved disease stabilization (SD) or better. Melflufen was generally well tolerated with manageable toxicity.
|All patients in the study were investigator assessed as non-responsive or non-tolerant to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). 36% of patients had received 3+ treatment regimens over the last 12 months. 91% of patients were double class refractory (IMiD + PI) and 79% anti-CD38 mAb refractory. 74% of the patients were triple class (IMiD + PI + Anti-CD38 mAb) refractory and 59% were alkylator refractory. 98% of the patients were refractory in last line of therapy.
|Rigel Pharmaceuticals, Inc.
Kissei Pharmaceuticals Co. Ltd.
|Fostamatinib Disodium Hexahydrate
|Chronic Immune Thrombocytopenia (ITP)
|Last month on 23 September, the sponsor announced that its collaboration partner, Kissei Pharmaceuticals Co., Ltd., has initiated a Phase III trial in Japan for administering Fostamatinib Disodium Hexahydrate (licensed in the U.S. under the brand name TAVALISSE®) in adult patients with chronic ITP. The efficacy and safety of orally administered Fostamatinib will be assessed by comparing it with placebo in a randomized, double-blind study.
|Fostamatinib is a spleen tyrosine kinase (SYK) inhibitor, which is a key signalling component in the body's immune process that leads to platelet destruction in ITP patients. In such patients, the immune system attacks and destroys the body's own blood platelets, which play an active role in blood clotting and healing. Chronic ITP sufferers may live with an increased risk of severe bleeding events that can result in serious medical complications or even death.
|Protalix BioTherapeutics, Inc.
Chiesi Farmaceutici S.p.A.
|PRX 102 (Pegunigalsidase Alfa)
|Fabry Disease with Impaired Renal Function
|This BALANCE Phase III clinical trial is a 24-month, randomized, double blind, active control study of PRX‑102 (Pegunigalsidase Alfa) in Fabry disease patients with impaired renal function. Patients previously treated with agalsidase beta for approximately one year and on a stable dose for at least six months were screened and then randomized to be switched and treated with 1 mg/kg of PRX‑102 or continue treatment with 1mg/kg of agalsidase beta. Patients receive intravenous infusions of 1mg/kg administered every two weeks. Subjects are randomized in a 2:1 ratio to PRX‑102 or agalsidase beta.
|Patients participating in the study are being also investigated if their renal function continues to deteriorate at the same rate while being treated with agalsidase beta as measured by eGFR slope. Cardiac assessment, Lyso-Gb3, pain, quality of life, immunogenicity, clinical events and pharmacokinetic and other parameters are also being evaluated. In addition, participating patients are being evaluated for safety and tolerability of PRX‑102. The sponsor's PRX 102 is an investigational, plant cell culture expressed enzyme, and a chemically modified version of, the recombinant alpha-Galactosidase-A protein. PRX 102 chemical cross-linking modified version of the enzyme uses short PEG chains, resulting in a more stable molecule with different pharmacokinetic parameters compared to the current available versions of the enzyme. In a pre-clinical Fabry mouse model, PRX 102 was observed to have favorable levels of enzyme activity in target organs affected by Fabry disease.
|Ocular Therapeutix, Inc.
|DEXTENZA (Dexamethasone Ophthalmic Insert)
|Allergic Conjunctivitis (AC)
|This Phase III clinical trial is of a U.S.-based, multi-centre, 1:1 randomized, double-masked, placebo-controlled study design anticipated to recruit approximately 80 subjects. The study’s primary objective is to assess the safety and efficacy of DEXTENZA (Dexamethasone Ophthalmic Insert) 0.4 mg at multiple time points during the 30 day period versus a placebo vehicle punctum plug using the Ophthalmic Research Associates’ modified Conjunctival Allergen Challenge (Ora-Cac®) Model for the treatment of ocular itching associated with AC.
|This clinical study is designed to evaluate the effect of DEXTENZA compared with a placebo on allergic reactions using a series of successive allergen challenges over a 30-day period as a clinical model for AC. DEXTENZA is an FDA-approved corticosteroid indicated for the treatment of ocular inflammation and pain following ophthalmic surgery. DEXTENZA is inserted into the canaliculus by the physician following ophthalmic surgery. A single DEXTENZA releases a 0.4 mg dose of dexamethasone for up to 30 days following insertion. DEXTENZA is preservative free, resorbable and does not require removal.
|This Phase I/IIa clinical trial is of a multicentre, open-label study design being conducted in the UK and Israel, with the possibilty to be expanded in the US and European countries within 2019. The primary objective of the study will be to assess the safety and tolerability of AGI-134, given both as monotherapy and in combination with an immune checkpoint inhibitor, in unresectable metastatic solid tumours.
|Additional study objectives will be to conduct a wide array of biomarker studies and to demonstrate the mechanism of AGI-134. Also, efficacy will be evaluated by clinical and pharmacodynamic parameters. AGI-134 is a synthetic, intratumuorally administered glycolipid of a supposedly unique mode of action, to label cancer cells with alpha-Gal, which then become the target of pre-existing anti-Gal antibodies, effectively triggering an immediate local anti-tumour response, as well as a follow-on systemic anti-tumour response targeting both the primary injected tumour and distal secondary tumours.
Week 23 Sept 2019 – 27 Sept 2019
|Alpha-1 Anti-Trypsin Deficiency (AATD)
|This Phase I clinical trial is of an open-label, two part, dose-escalating, study design of INBRX-101 (rhAAT-Fc). Part one will be comprised of a single ascending dose administration of INBRX-101 and part two will comprise of multiple ascending dose (MAD) administrations of INBRX-101. The planned dosing schedule is intravenous administration every 3 to 4 weeks.
|INBRX-101 is an Fc-fusion protein-based therapeutic candidate composed of a modified recombinant version of human alpha-1 antitrypsin for the treatment of patients with AATD. AATD is a genetically defined rare respiratory disease noted for its progressive destruction of lung tissue that leads to COPD and emphysema.
|This Phase I trial is of a multi-centre, open-label, dose-escalation study design to evaluate the safety, tolerability, and pharmacokinetics of RBN-2397, as well as initial signs of anti-tumour activity in patients with advanced-stage solid tumours. The study goals will be to establish the recommended dose for future clinical investigation and to investigate pharmacodynamic readouts and predictive biomarkers.
|RBN-2397 is a first-in-class PARP7 inhibitor. PARP7 in tumours. has been shown to play a key role in cancer survival. Much of the sponsor's research has revealed that many cancer cells rely on PARP7 for intrinsic cell survival, and that PARP7 allows cancer cells to “hide” from the immune system. This clinical trial is comprised of a dose escalation phase, which will be followed by a number of expansion cohorts asessing RBN-2397 in patients with various tumour types, including squamous cell carcinoma of the lung, in which PARP7 has been shown to be genetically amplified.
|Infinity Pharmaceuticals - Arcus Biosciences
|IPI-549 in combination with Arcus’ AB298 and Doxil®
|Advanced Triple Negative Breast Cancer (TNBC)
|Arcus Biosciences initiated a Phase I/Ib study, in collaboration with the sponsor, assessing IPI-549 in a novel combination regimen with AB298, Arcus's dual adenosine receptor antagonist, and Doxil®, a chemotherapy, in patients with advanced TNBC.
|IPI-549 is a first-in-class, oral immuno-oncology development candidate that selectively inhibits PI3K-gamma as demonstrated in multiple clinical studies. This Phase I study in collaboration with Arcus will evaluate IPI-549 in combination with AB928, Arcus's dual adenosine receptor antagonist, and chemotherapy in patients with TNBC. With the addition of MARIO-275 and MARIO-3 to the ongoing MARIO-1 study, the sponsor will be assessing IPI-549 in the anti-PD-1 refractory, I/O-naïve and front-line settings (see below).
|China MediTech Limited
|Relapsed or Refractory Lymphoma
|This Phase I/Ib clinical trial is of a multi-centre, open-label, two-stage study design to assess safety, tolerability, pharmacokinetics and preliminary efficacy of HMPL-689 monotherapy in relapsed and/or refractory non-Hodgkin lymphoma patients. During the initial dose-escalation stage, the primary study objective will be to determine the maximum tolerated dose or the recommended Phase II dose (“RP2D”).
|Safety, tolerability and preliminary efficacy of HMPL-689 at the RP2D will be further investigated in a subsequent dose-expansion stage in which several subtypes of lymphoma patients will be assessed. HMPL-689 is a novel, potentially best-in-class, highly selective and potent small molecule which inhibits the isoform PI3Kδ. HMPL-689 was designed for superior PI3Kδ isoform selectivity, in particular to not inhibit PI3Kɣ (gamma), to minimize the risk of serious infection caused by immune suppression. PI3K signaling is mediated by four different catalytic isoforms (p110α, β, ɣ, δ). The δ (delta) isoform is the most critical isoform and a proven target in the BCR signaling pathway. This isoform is confined to haematopoietic cells and is highly expressed in lymphoid cells.
|Rocket Pharmaceuticals, Inc.
|Severe Leukocyte Adhesion Deficiency-I (LAD-I)
|This Phase I/II clinical trial is of a non-randomized, open-label study design and is anticipated to recruit nine paediatric patients globally. The Phase I portion of the trial is expected to enroll two patients and will assess the safety and tolerability of RP-L201.
|The Phase II portion of the clinical trial will assess overall survival at multiple sites globally both in the U.S. and E.U.. RP-L201 is the sponsor’s lentiviral vector (LVV)-based gene therapy for the treatment of severe LAD-I that was in-licensed from the Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT: Madrid, Spain). The lentiviral vector was developed in a collaboration between The University College of London (UCL) and CIEMAT. Severe LAD-I is a rare, autosomal recessive paediatric disease caused by a mutation of the ITGB2 gene that encodes for the beta-2 integrin component CD18. CD18 is a key protein that assists in the leukocyte adhesion and extravasation processes in blood vessels to combat infections. As a result, during infancy, severe LAD-I children suffer from recurrent life-threatening bacterial infections that respond poorly to antibiotics and require frequent hospitalizations.
|PI-549 in combination with Tecentriq® and Abraxane® (Nab-Paclitaxel)
|Front-line Triple Negative Breast Cancer (TNBC)
|This Phase II clinical trial (MARIO-3), is a multi-arm study being conducted in collaboration with Roche/Genentech assessing IPI-549 in combination with Tecentriq® and Abraxane® (Nab-Paclitaxel) in front-line TNBC. Following on from the results of Roche's IMpassion130 study in which Tecentriq® and Abraxane® received accelerated approval in PDL1+ TNBC patients, MARIO-3 is assessing the addition of PI-549 to this regimen in both PDL1+ and PDL1- front-line TNBC patients. MARIO-3 also includes a cohort assessing IPI-549 in combination with Tecentriq® and Avastin® (Bevacizumab) in front-line PDL1+ and PDL1- renal cell cancer (RCC) patients.
|IPI-549 is a first-in-class, oral immuno-oncology development candidate that selectively inhibits PI3K-gamma as revealed in multiple clinical studies. The sponsor has recently initiated MARIO-275 and MARIO-3, in addition to a Phase I study in collaboration with Arcus Biosciences. MARIO-275 is a global, randomized, combination study of IPI-549 combined with Opdivo® (Nivolumab)
in I/O naïve urothelial cancer patients. MARIO-3 is the first IPI-549 combination study in front-line advanced cancer patients and is assessing IPI-549 in combination with Tecentriq® and Abraxane® (Nab-Paclitaxel) in front-line TNBC and in combination with Tecentriq® and Avastin® (Bevacizumab) in front-line RCC. The Phase I study in collaboration with Arcus will evaluate IPI-549 in combination with AB928, Arcus's dual adenosine receptor antagonist, and chemotherapy in patients with TNBC. With the addition of MARIO-275 and MARIO-3 to the ongoing MARIO-1 study, the sponsor will be assessing IPI-549 in the anti-PD-1 refractory, I/O-naïve and front-line settings.
Week 26 Aug 2019 – 30 Aug 2019
|Hypertrophic Cardiomyopathy (HCM)
|This Phase I clinical trial is of a randomized, placebo-controlled, single and multiple-ascending dose study design that will enroll adult healthy volunteers into cohorts of eight, randomized 3:1 to MYK-224 or placebo. The primary study objectives will be to evaluate the safety, tolerability and pharmacokinetics of MYK-224.
|As secondary study objectives, pharmacodynamic effects on cardiac function and dimensions will also be assessed using echocardiography. HCM is a progressive disorder in which the excessive contraction of the heart muscle and reduced ability of the left ventricle to fill can lead to debilitating symptoms and cardiac dysfunction. MYK-224 selectively targets cardiac myosin, the sarcomeric proteins of the heart muscle, in other words the heart’s motor protein, with the aim of normalizing contractility and filling.
|Human Papillomavirus (HPV) associated cancers with HPV type 16
|This Phase I, two part, open label clinical trial will evaluate the safety and efficacy of KITE-439. Adult, HLA-A201 positive patients with relapsed/refractory HPV16 solid tumors will receive cyclophosphamide and fludarabine conditioning chemotherapy followed by a single dose of KITE-439. The trial will be conducted in two parts, the first part of the study will evaluate the dose-limiting toxicity after a single dose of KITE-439. Based on the selected dose, part two of the study will evaluate the efficacy of KITE-439 by measuring the objective response rate.
|HPV type 16-induced cancers, a strain that causes about 70% of all cervical cancers worldwide, are ideal candidates for targeted T cell therapy due to their nonself antigens. Those antigens can be readily recognized by immune cells inducing T cell activation. The study makes use of genetically engineered human T cells with KITE-439 receptors for the treatment of patients with relapsed or resistant HPV-associated cancers. This engineered receptor works on targeting antigens expressed in cancer cells that are infected by HPV, leading to a T cell activation against the cells.
|This Phase I, single centre, dose escalation clinical trial will assess SNK administered intravenously once a week for four weeks at three different dosing levels. Nine patients will be recruited in the study to evaluate the safety and tolerability of SNK in adults with mild to severe plaque psoriasis. The clinical trial site will be at Angeles Hospital, in Tijuana, Mexico.
|The sponsor's SNK product is an autologous therapy made by harvesting a small number of a patient's immune cells. After harvesting, NK cells are isolated from the blood, purified, activated, and expanded in a cGMP facility. The activated NK cells, known as "SNK," are reinfused in the patient to suppress the inflammatory response attributed to psoriasis.
|In this on-going Phase Ib study, FOR-6219 will be administered to premenopausal women to evaluate its effect on the endometrium by measuring changes in endometrial thickness and endometrial estrogen levels. In addition to these local effects, systemic hormone levels will also be monitored. Secondary endpoints will be based on safety and tolerability.
|The Phase Ia study results of FOR-6219 revealed single doses from 2mg up to 175mg and multiple doses up to 150mg twice daily over 10 days were found to be safe and well tolerated in 36 healthy postmenopausal women. The pharmacokinetics (PK) of FOR-6219 was dose-proportional and a steady state was attained within 3 days. The observed elimination half-life was in the range of 16 to 18 hours, inferring potential for once daily dosing. The PK profiles of FOR-6219 were similar in a fasted and fed state meaning that FOR-6219 can be administered with or without food. FOR-6219 is a first-in-class drug candidate that selectively targets endometriosis lesions without effecting systemic estrogen. The mode of action of FOR-6219 lies in its inhibitory effect of the conversion of low potency estrone into highly potent estradiol in endometrial tissues. The key differentiating pharmacology of FOR-6219 compared to currently available treatments is its selective activity and the ability to act locally in the target tissues, without adversely affecting systemic hormone levels.
|BioInvent International AB
|BI-1206 in combination with Pembrolizumab (Keytruda)
|This Phase l/lla study will investigate the drug combination of BI-1206, one of the sponsor's proprietary anti-FcγRllB antibodies, and Pembrolizumab (Keytruda®), a leading anti-PD1 antibody, in patients with advanced solid tumours, who have been previously treated with anti-PD1 or anti-PD-L1 antibodies. This clinical trial is of a multicentre, dose-finding, consecutive-cohort, open-label study design.
|The premise to initiating this clinical trial program is based on the sponsor's recent preclinical data demonstrating the ability of BI-1206 to address an important mechanism of resistance to PD1 inhibition, providing a way to enhance anti-tumour immune responses in patients with solid tumours. The sponsor's proprietary F.I.R.S.TTM technology platform simultaneously identifies both targets and the antibodies that bind to them, generating new drug candidates for investigation.
|Rocket Pharmaceuticals, Inc.
|Fanconi Anaemia (FA)
|This open-label Phase II study will enroll up to five paediatric patients in Europe. The clinical trial will enroll paediatric patients who have not developed severe bone marrow failure. Patients will receive a single intravenous infusion of RP-L102 that utilizes “Process B” which incorporates enhanced stem cell enrichment, transduction enhancers and commercial-grade vector and manufacturing without the use of any conditioning treatment. The study is designed to evaluate the benefit/risk profile of RP-L102. The primary endpoint of the study is the emergence of mitomycin-C (MMC) resistance in bone marrow colony forming (progenitor) cells. A surrogate endpoint is the diepoxybutane (DEB) chromosomal stability of peripheral blood T-lymphocytes. Sensitivity to DNA-damaging agents (MMC and DEB) is a phenotypic hallmark of FA. Additional outcomes include stability or increase in blood counts with no significant worsening in anaemia, neutropenia or thrombocytopenia and peripheral blood genetic correction, as demonstrated by vector copy number (VCN), including progressive increases in peripheral blood VCN over the months subsequent to infusion.
|FA is a rare pediatric disease characterized by bone marrow failure, malformations and cancer predisposition. The primary cause of death among patients with FA is bone marrow failure, which typically occurs during the first decade of life. Allogeneic haematopoietic stem cell transplantation (HSCT), when available, corrects the haematologic component of FA, but needs myeloablative conditioning, which is highly toxic for the patient. HSCT is frequently complicated by graft versus host disease and also increases the risk of solid tumours, particularly upper aerodigestive tract squamous cell carcinomas. Roughly 60% to 70% of patients with FA have a FANCA gene mutation, which encodes for a protein essential for DNA repair. Mutations in the FANCA gene leads to chromosomal breakage and increased sensitivity to oxidative and environmental stress.
|Mild to moderate Ulcerative Colitis (UC)
|This global Phase II clinical trial is of a randomized, placebo-controlled, double-blind, parallel-group, multicentre study design to investigate the safety, efficacy and tolerability of BT-11 compared to placebo in patients with mild to moderately-active UC. The study will recruit 195 patients with mild to moderate UC in 11 countries with 60 sites throughout the U.S., Europe and Eastern Europe. Patients will be randomized to receive one of two doses of BT-11 (500 or 1,000 mg) or placebo for a 12-week induction phase followed by a maintenance phase. The study’s primary endpoint will assess the effect of treatment with once-daily doses of BT-11 tablets or placebo on clinical remission rate at week 12, as defined by total Mayo score ≤ 2 with all sub-scores ≤1.
|UC is a chronic inflammatory disease of the large intestine caused by the body’s immune system sending white blood cells to the intestinal lining thus eliciting chronic inflammation and ulcerations giving rise to abdominal discomfort and frequent emptying of the lower intestines. BT-11 is a first-in-class, gut-restricted small molecule IND of oral formulation that targets the Lanthionine Synthetase C-Like 2 (LANCL2) pathway that regulates the immunological state of the gastrointestinal tract. By activating the LANCL2 pathway and modulating the interactions between immunological and metabolic signals in immune cells, BT-11 creates a favorable regulatory microenvironment in the gut tissue wall, decreasing the production of key inflammatory mediators and increasing anti-inflammatory markers in regulatory T cells (Treg) within the site of inflammation.
|Inovio Pharmaceuticals, Inc.
|Human Papillomavirus (HPV)-related anal High-grade Squamous Intraepithelial Lesions (anal HSIL)
|This Phase II clinical trial is of an open-label, multi-centre study design to evaluate the safety and efficacy of VGX-3100 administered by the Sponsor's CELLECTRA® delivery system in adult men and women with anal HSIL caused by HPV-16 and/or HPV-18. In a randomized, double-blind, placebo-controlled Phase IIb proof-of-concept study in 167 adult women with histologically documented HPV-16/18 cervical HSIL, treatment with VGX-3100 resulted in a statistically significant greater regression of cervical HSIL and clearance of HPV-16/18 infection versus placebo.
|Anal HSIL or dysplasia is an orphan disease and a common precursor to developing anal cancer with an estimated mortality rate for this year so far of more than 1,280 deaths in the United States alone. Anal HSIL is estimated to occur in nearly 20,000 new cases annually. VGX-3100 is a DNA-based immunotherapy stimulating a specific immune response to HPV-16 and HPV-18, which targets the infection and causes destruction of precancerous cells.
|Knopp Biosciences LLC
|This 12-week biomarker Phase II clinical trial will randomize an estimated 100 patients with eosinophilic asthma to evaluate the eosinophil response to three different doses of oral Dexpramipexole. The primary outcome measure of this randomized, double-blind, placebo-controlled study is the change in blood absolute eosinophil count from Baseline to Week 12.
|The secondary outcome measures of this study include changes in pre-bronchodilator FEV1 and asthma control outcomes (ACQ-7 questionnaire) from baseline to week 12. Dexpramipexole although prescribed as an oral steroid-sparing agent in hypereosinophilic syndromes, its mechanism of action is yet unclear.
|Emalex Biosciences, Inc.
|Tourette Syndrome (TS)
|This Phase IIb clinical trial of double-blind study design of Ecopipam HCl oral dosing in paediatric patients (aged >6 to <18 years) with TS is being conducted in multiple clinical sites in the United States, Canada, and the European Union. An estimated 150 patients will be randomized to either Ecopipam HCl 2 mg/kg/day or an equivalent placebo for 12 weeks. Upon completion of the study patients will be eligible to enroll in a one-year open-label safety extension study where all patients will receive Ecopipam HCl 2 mg/kg/day.
|TS is a neurological disorder characterized by motor or vocal tics that begins during childhood and is not associated with any medication etiology, other medical reasons, or a confirmed neurological abnormality. Ecopipam HCl is an investigational first-in-class drug being investigated in paediatric patients for the treatment of TS and for childhood onset fluency disorder (stuttering) in adults. Ecopipam selectively blocks the actions of the neurotransmitter dopamine at the D1 receptor.
|Satsuma Pharmaceuticals, Inc.
|This Phase 3 EMERGE efficacy clinical trial of candidate STS101 is of a multi-centre, single-dose, randomized, double-blind, placebo-controlled, parallel group study design to be undertaken in approximately 1,140 migraine patients in the United States. The EMERGE participanting patients will be randomized (1:1:1) to receive one of three treatments: STS101 DHE 3.9 mg, STS101 DHE 5.2 mg or equivalent placebo and will be instructed to treat their next migraine attack of at least moderate pain severity with the allocated blinded study medication. The two co-primary endpoints of the EMERGE trial to be assessed at two hours after STS101 administration are freedom from pain and freedom from most bothersome symptom (from among photophobia, phonophobia or nausea).
|The EMERGE trial design incorporates several secondary endpoints and prospective evaluations of the clinical performance of STS101 in a number of patient subgroups that could differentiate the clinical profile of STS101. STS101 is a drug-device combination of a proprietary dry-powder formulation of Dihydroergotamine Mesylate (DHE), which can be swiftly and conveniently self-administered with a proprietary pre-filled, single-use, nasal delivery device. DHE is an antimigraine agonist to the serotonin (5-HT) -1B, -1D and -1F receptors. It also interacts with other serotonin, adrenergic and dopamine receptors.
Week 19 Aug 2019 – 23 Aug 2019
|Coordination Pharmaceuticals Inc.
|This Phase I clinical trial is of a prospective, open-label, single-arm, non-randomized study design of CPI-200 administration in patients with advanced tumours. The primary study objectives include determining maximum tolerated dose, pharmacokinetics and preliminary anti-tumour activity of CPI-200.
|CPI-100 is a novel nanoscale coordination polymer (NCP) containing two synergistic new molecular entities (NMEs) to activate tumor microenvironments for combination therapy with an immune checkpoint inhibitor. The sponsor is also conducting Phase I studies of CPI-100 and RiMO-301 on patients with advanced tumours. RiMO-301 enhances the efficacy of X-ray radiotherapy via the unprecedented radiotherapy-radiodynamic therapy (RT-RDT) mode of action to improve the efficacy of X-ray radiotherapy. A single escalation dose of RiMO-301 is intratumorally injected in a 3+3 study design to identify the recommended dose and dosing volumes.
|RET-altered non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and other advanced solid tumours
|The sponsor on 13 August this month initiated this Phase I registrational study in China for BLU-667, which was discovered by the company's partner Blueprint Medicines. This study is a part of the ongoing, global Phase I ARROW trial that is designed to assess the overall response rate (ORR), duration of response, pharmacokinetics, pharmacodynamics and safety of BLU-667 in patients with RET-altered non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and other advanced solid tumours.
|Rare genetic alterations continue to be discovered and some become novel targets for therapy. The RET gene is one of such rare genetic alteration of NSCLC. NSCLC accounts for 80-85% of all lung cancers and RET fusions occur in approximately 1-2% of all NSCLC cases. MTC accounts for 2-5% of all thyroid cancers, and RET mutations occur in nearly all hereditary MTC patients and approximately 50% of all sporadic MTC patients. Currently there is no effective standard of treatment approved for MTC patients in China. BLU-667 is an orally available anti-tumour candidate, and updated results from the ARROW clinical trial have revealed it to be a highly selective and potent RET inhibitor.
|Bio-Thera Solutions, Ltd.
|Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis (AS) and Ulcerative Colitis
|This Phase I clinical trial will compare the pharmacokinetics and safety of BAT2506, a proposed biosimilar of Simponi® (Golimumab), to EU-sourced Simponi® in normal healthy volunteers. The study is of a randomized, double-blind, two-arm, parallel group design that is anticipated to recruit approximately 182 healthy volunteers. Each study subject will be administered a single subcutaneous dose of either BAT2506 or EU-sourced Simponi®.
|Simponi® (Golimumab) is a human monoclonal antibody which is used as an immunosuppressive drug and Simponi® is a registered trademark of Janssen Biotech, Inc. Golimumab targets tumor necrosis factor alpha, a pro-inflammatory molecule and hence is a TNF inhibitor.
|MNK-6106 (L-Ornithine Phenylacetate)
|Hepatic Cirrhosis and Hepatic Encephalopathy (HE)
|This Phase IIa clinical trial is of a comparator, randomized, open-label study design to evaluate the pharmacodynamics, pharmacokinetics and safety of orally administered MNK-6106 (L-Ornithine Phenylacetate) versus Rifaximin in patents with hepatic cirrhosis and a prior history of episodes of HE. The trial will enroll adult men and non-pregnant women with hepatic cirrhosis who have a history of at least two or more documented episodes of HE in the last 12 months, with one in the last six months, and who are hyperammonemic at the time of screening. Roughly 48 patients who meet eligibility criteria will be randomly assigned to one of four groups. Those in three experimental arms will receive MNK-6106 for five days with food, according to different dosing regimens – 2 grams, three times daily; 4 grams, twice daily; and 4 grams, three times daily. The fourth group, the active comparator group, will receive 550 milligrams of Rifaximin twice daily for five days with food.
|The primary objective of this study is to assess the pharmacological effect of MNK-6106 through the assessment of plasma ammonia concentration as a pharmacodynamic marker following oral administrations of the MNK-6106 candidate with Rifaximin as a control in patients with hepatic cirrhosis and a history of prior episodes of HE. The study's endpoints are the absolute and percentage change in plasma ammonia from baseline, in a timeframe from baseline to five days. MNK-6106 (L-Ornithine Phenylacetate) mode of action is that it acts as an ammonia scavenger. HE is a critical neurocognitive complication of chronic liver disease. It is associated with elevated circulating ammonia levels stemming from end stage cirrhosis. Symptoms range from mildly altered mental status to coma or death.
|10 Percent Intravenous Immunoglobulin
|Primary Immunodeficiency (PI) Diseases
|This CARES10 ( C linical A ssessment of pha R macokinetics, E fficacy, S afety of a 10 % Ig) Phase III clinical trial will be conducted in the United States and/or Canada and will be of an open-label, prospective, multi-centre study design to evaluate efficacy, safety and pharmacokinetics of a 10 percent intravenous immunoglobulin administration to adult patients with PI diseases. CARES10 may also recruit a limited number of paediatric patients for the purpose of acquiring preliminary data in that population. it is anticipated a total of approximately 50 patients will be enrolled in this study.
|PI is an umbrella term for a group of more than 350 rare and chronic disorders in which part of the body’s immune system is either missing or not functioning properly.
Week 22 July 2019 – 26 July 2019
|Emmaus Life Sciences, Inc.
|Pharmaceutical Grade L-Glutamine (PGLG)
|This Phase I clinical trial will investigate the treatment of diverticulosis with pharmaceutical-grade L-glutamine (PGLG) utilising the same PGLG as in the branded oral powder Endari®. The study seeks to assess change in the number and size of colonic diverticula and evaluate safety in a total of ten patients at multiple study sites.
|According to the sponsors, there is no approved treatment for diverticulosis which a high-fibre diet and a mild analgesic is often used to relieve symptoms of pain and discomfort. The sponsor holds patents related to formulations composed of PGLG and methods involving administration of PGLG for the treatment of diverticulosis in the U.S., Japan, Australia, Mexico, China, Indonesia, Korea and Russia.
|Enanta Pharmaceuticals, Inc.
|Hepatitis B Virus (HBV)
|This Phase Ia/b clinical trial is of a randomized, double-blind, placebo-controlled design and will be conducted in two parts. The first part (Part 1), will assess the safety, tolerability and pharmacokinetics (PK) of single ascending doses (SAD) and multiple ascending doses (MAD) of EDP-514 in healthy subjects. For the second part (Part 2), the antiviral efficacy of EDP-514 in nucleos(t)ide-reverse-transcriptase (NUC)-suppressed patients with chronic HBV infection will be evaluated. The clinical trial intends to recruit approximately 98 subjects and to assess up to 6 dose cohorts, with oral formulated EDP-514 administered once daily. Upon completion of the Part 1 study, the SAD and MAD portion in healthy subjects, the Part 2 study will also assess safety, PK and antiviral data of EDP-514 in NUC-suppressed patients with chronic HBV infection.
|EDP-514, is a novel class II hepatitis B virus (HBV) core inhibitor. Core inhibitors, also known as capsid assembly modulators or core protein allosteric modulators, are a novel class of replication inhibitors that have been demonstrated to act at multiple steps in the HBV lifecycle. Preclinical studies have shown that EDP-514 is a potent inhibitor of HBV replication and prevents the de novo formation of new cccDNA in primary human hepatocytes when given early during HBV infection. The HBV has potential to cause a life-threatening liver infection and is transmitted through contact with the blood or other bodily fluids of another HBV infected individual. Approximately the worldwide incidence of chronic infection of HBV stands at 250 million and as many as 15 to 25% of these infected subjects develop chronic liver disease, including cirrhosis, liver cancer and/or liver dysfunction. Current treatments for HBV provide minimal cure rates complicated by serious side effects.
|Auris Medical Holding Ltd.
|Antipsychotic-Induced Weight Gain and Somnolence
|This Phase Ib study with AM-201 is being conducted at a single clinical site in Europe. The study recruited in total 50 healthy volunteers who received either AM-201 or placebo in combination with the antipsychotic drug olanzapine over four weeks. This clinical trial is evaluating five different doses of AM-201 under a dose escalation study protocol. The primary efficacy outcome for the trial will be the reduction in weight gain.
|The secondary outcome of the study will be the reduction in somnolence or drowsiness. AM-201 is the code name which the sponsor has assigned for developing intranasal betahistine as a preventive medicine of antipsychotic-induced weight gain and somnolence. The H1 histamine receptor controls appetite and wakefulness and there are numerous antipsychotic drugs which are recognised as a H1 histamine receptor inhibitors. Thus blockage of this key receptor results in weight gain and somnolence as side effects. As an H1 receptor agonist, betahistine is thought to counteract the antipsychotics’ inhibitory effects; moreover, betahistine inhibits presynaptic H3 histamine autoreceptors, thus enhancing histamine release and consequently augmenting betahistine’s direct agonistic effects on H1 receptors.
|4D Pharma Plc
|This Phase I/II clinical trial is of a double-blind, placebo-controlled, multicentre study design which will administer MRx-4DP0004 in patients with poorly controlled asthma. The clinical trial will recruit 90 asthma patients not adequately controlled on their current inhaler maintenance therapy. Study patients will take MRx-4DP0004 in addition to existing maintenance therapy. This is the world's first clinical study of a live biotherapeutic in patients with poorly controlled asthma. The primary study endpoints are safety and tolerability of MRx-4DP0004 when administered in combination to a long-term maintenance therapy.
|The secondary endpoints of the study include reduction of asthma symptoms, exacerbations, hospitalisations and the attainment of improved asthma control. MRx4DP0004 has shown potent and significant efficacy in healthcare standard preclinical models of steroid-resistant severe asthma. It demonstrated reduction of both neutrophils and eosinophils in prophylactic as well as therapeutic settings. The efficacy was also reflected in a reduction in histopathological lung inflammation, and specific subsets of T cells and dendritic cells. Significantly, MRx4DP0004 outperformed the anti-IL-17 positive control in this model and was able to reduce airway neutrophils and eosinophils concurrently, which is not achievable with existing asthma prescription medicines.
|This Phase Ib/II study will investigate VE416 as a monotherapy, and in combination with an oral peanut immunotherapy using a randomized, double-blind, placebo-controlled study design. This clinical trial will recruit up to 40 patients who are 12 years of age and older. The primary study endpoints are safety of VE416 and amount of peanut protein tolerated during a double-blind, placebo-controlled food challenge following treatment.
|Additionally the study will evaluate the efficacy of VE416 in inducing higher rates of clinical tolerance and reducing adverse effects in patients undergoing peanut oral immunotherapy. VE416 is an orally administered investigational live biotherapeutic product composed of a defined bacterial consortium. It is produced from pure, clonal bacterial cell banks, which yield a drug product of uniform composition in powdered form and free of any pathogenic strains, bypassing the need to rely on faecal donor material with inconsistent composition. In preclinical sensitised mice models, VE416 induced protective immunoregulatory responses and reduced anaphylaxis and allergic symptoms.
|ActoBio Therapeutics, Inc.
|AG019 (and combined with Teplizumab (PRV-031) for adult patients)
|Early-Onset Type 1 Diabetes (T1D)
|This Phase Ib/IIa study will investigate AG019 administered for 8 weeks in patients 12-17 years of age and in adults in combination with Teplizumab (PRV-031) for the first 12 days as compared to placebo. In pre-clinical studies using a diabetic mouse model, dosing of AG019, in association with a short-term treatment with a systemic anti-CD3 monoclonal antibody, induced reversion to normal blood sugar levels in 60% of the mice and reversed the disease in 89% of mice treated at early stage of the disease.
|AG019 is an oral capsule formulation consisting of bioengineered and modified Lactococcus lactis designed to specifically deliver human proinsulin and the tolerance-enhancing cytokine human interleukin-10 to the mucosal lining of the gastro-intestinal tissues. In the Phase IIa stage of the study, AG019 will be utilized in combination with Teplizumab, a Phase III anti-CD3 monoclonal antibody in development for the interception and prevention of clinical T1D, pursuant to a collaboration with Provention Bio. Inc.
|Biohaven Pharmaceutical Holding Company Ltd.
|Treatment Refractory Trigeminal Neuralgia
|This Phase II clinical trial will recruit patients for a double-blind, placebo-controlled, crossover study design performed at the Johns Hopkins Medical Center. Investigators will assess the efficacy and safety of Rimegepant in treating Trigeminal Neuralgia in patients who failed to respond adequately to previous pharmacotherapy. The primary outcome measure of the study is the change in a patient's average Numeric Pain Rating Scale between the two treatment phases of the study.
|Trigeminal neuralgia is a neuropathic pain disease characterized by recurrent, paroxysmal, lancinating pain in the distribution of one or more branches of the trigeminal nerve resulting in episodes of severe facial pain lasting seconds to minutes, several times per day, causing significant disability. Irregular release from the trigeminal nerve of the neuropeptide calcitonin gene-related peptide (CGRP) is considered to be the etiological basis in the development of neuronal sensitization and neuropathic pain associated with the pathophysiology of trigeminal neuralgia. Rimegepant is the sponsor's lead oral, selective and potent small molecule calcitonin gene-related peptide (CGRP) receptor antagonist also presently being developed for the treatment of migraine (refer to the entry below).
|Biohaven Pharmaceutical Holding Company Ltd.
|For this Phase III pivotal clinical trial of Rimegepant for the acute treatment of migraine, the results have been published in the July 12, 2019 issue of the New England Journal of Medicine (NEJM). A total of 1,186 patients in the study were randomized to receive a single dose of either Rimegepant or placebo. A broad spectrum of clinically meaningful benefit compared to placebo was demonstrated across multiple outcome measures, including the co-primary endpoints of pain freedom and freedom from the most bothersome symptom at two hours post-dosing. A single 75 mg dose of Rimegepant was shown to have significant superiority on pain freedom and pain relief at 2 hours, freedom from the most bothersome symptom at 2 hours as well as photophobia and phonophobia at 2 hours. Furthermore, Rimegepant was numerically superior in terms of sustained pain freedom and pain relief through 48 hours and the ability to return to function at 2 hours.
|Rimegepant was generally well tolerated with a low occurrence of side effects. The most common adverse incidents were nausea, occurring in 1.8% of Rimegepant patients, as compared to 1.1% of patients on placebo and urinary tract infection (UTI), occurring in 1.5% of Rimegepant patients, as compared to 1.1% of patients on placebo. Serious adverse events were observed in one patient in the Rimegepant group (back pain) and two patients in the placebo group (Chest Pain and UTI). Furthermore, Rimegepant demonstrated a liver safety profile similar to placebo in this acute treatment trial. Rimegepant is the sponsor's orally-dosed calcitonin gene-related peptide (CGRP) receptor antagonist, which it is developing as a treatment for migraine. Rimegepant represents a novel mechanism that targets the underlying pathophysiology of migraine without causing vasoconstriction.
|Moderate to Severe Rheumatoid Arthritis (RA)
|This Phase III clinical trial named ContRAst is the first in RA drug development to include head-to-head comparisons of Otilimab with current treatments across all pivotal studies. The study programme will compare Otilimab against two treatments with different modes of actions: Tofacitinib (a Janus Kinase (JAK) inhibitor) and Sarilumab (inhibitor of IL-6 receptor signaling). ContRAst which comprises three pivotal studies and a single long-term extension study, will also include a broad range of difficult-to-treat patients who have had an inadequate response to or have been unable to tolerate currently available treatments.
|The first dosing of patient in the ContRAst programme translates to a milestone payment of 22 million Euros to MorphoSys, from which the sponsor licensed rights to the drug candidate in 2013. RA is a chronic and debilitating autoimmune disorder with a high clinical priority to find alternative treatment options for patients suffering from moderate to severe forms of the disease.
|BiondVax Pharmaceuticals Ltd.
|This placebo-controlled, pivotal, clinical efficacy, Phase III study will investigate safety and effectiveness of the M-001 vaccine as a single therapy in reducing influenza symptoms and severity in approximately 12,000 adults aged 50 years and older, with at least half aged 65 and older. A total of 4,094 subjects were recruited in the study's first cohort prior to the 2018/19 flu season, and upon review of the safety profile, the Data Safety Monitoring Board gave approval for the sponsor to proceed with the study's second cohort. Approximately 8,000 subjects are being enrolled in the study's second cohort (2019/20 flu season) in 85 sites in seven countries in eastern Europe.
|M-001 is a universal influenza vaccine candidate being clinically developed to improve upon currently marketed strain-specific vaccines in a number of ways. It is designed as a common denominator to influenza viruses and results from six completed clinical trials demonstrating that M-001 induces an immune response to a broad range of influenza strains. Moreover, M-001's single formulation enables year-round production, vaccination, and stockpiling.
Week 1 July 2019 – 5 July 2019
|Multiple Sclerosis (MS)
|This is a double-blinded trial being conducted at a clinical centre in the Netherlands, where T20K will be administrated by infusion to healthy male volunteers. The study will assess the level of T20K in the blood after administering one or two doses of the drug candidate. The primary study objective is to evaluate the safety and tolerability of T20K in humans and is being conducted in collaboration with QPS Netherlands, a CRO located in Groningen, Netherlands.
|T20K is being developed as a first line treatment for MS. T20K is naturally derived from plant protein and has demonstrated in a preclinical animal model to reduce MS symptoms after oral administration by inhibiting pro-inflammatory cytokines such as IL-2. To date no signs of toxicity have been observed at therapeutic dosages. Results from preclinical studies also show that T20K could be used to mitigate or even prevent MS events and with its prophylactic properties, to potentially even delay MS disease progression.
|This is a Phase I study designed to assess the safety, tolerability and efficacy of PD-L1 t-haNK cell therapy in patients with solid tumours. Upon completion of safety testing in this Phase I study, the sponsor plans to combine this PD-L1 t-haNK cell therapy with other immunomodulatory agents including NabFc-N803, a IL15 cytokine super agonist and Adenovirus or yeast vectors.
|PD-L1 t-haNK cell therapy is a novel, NK cell-based immuno-oncology therapy that incorporates a PD-L1 based Chimeric Antigen Receptor (CAR) engineered into the sponsor's proprietary haNK NK cell, which also includes the high affinity variant of the CD16 receptor (V158 FcγRIIIa) to mediate antibody dependent cellular cytotoxicity. In preclinical studies, the use of this next generation PD-L1 t-haNK therapy, in a tandem-specific manner has demonstrated to significantly enhance cancer cell annihilation and improve overall response rates.
|Clinical Neoantigen Peptides
|On 25th June, last month, the sponsor announced that they have successfully in collaboration with undisclosed partners initiated patient recruitment for their Phase I study with patients receiving their first doses of the neoantigen vaccines. Early results are anticipated in the fourth quarter of 2019. The sponsor is solely responsible for production of clinical neoantigen peptides, the core active ingredient in the vaccine candidate tailored to tumours of individual patients.
|Neoantigens, or tumour-specific antigens, are peptide sequences uniquely expressed in proteins from the tumour cells of individual patients. The sponsor's in vitro synthesised neoantigen peptides represent the core active ingredient of these anti-cancer vaccines. The design of the vaccines is intended to stimulate the patient's immune system to attack the tumour, thus inhibiting or reducing the proliferation of tumour cells. Neoantigen vaccination is a new generation personalized cancer treatment undergoing a huge growth phase in clinical development.
|Advanced Malignant Tumours
|This Phase I study will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of TJC4 in patients with advanced solid tumours and lymphoma when administered as a single agent and in combination with other cancer treatment agent(s).
|CD47 is a glycoprotein over-expressed in a wide variety of tumours and sends a "don't engulf me" signal to tumour-engulfing macrophages via its ligand known as SIRPα. Inhibition of CD47 by TJC4 enables macrophages to engulf malignant tumour cells as a potential treatment strategy for cancers.
|APL-1202 in combination with BCG (Bacillus Calmette Guerin)
|Non-Muscle Invasive Bladder Cancer (NMIBC)
|The primary objective of this Phase Ib US study is to assess the safety, tolerability, and pharmacokinetic profile of APL-1202 when administered in combination with intravesical BCG. Recruited patients are NMIBC subjects who have undergone at least one induction course of intravesical BCG.
|APL-1202 is the first oral and reversible methionine aminopeptidase II type (MetAP2) inhibitor of its class currently under clinical development worldwide. Its mechanism of action is novel in the blockade of both tumour cell growth and angiogenesis. APL-1202 is currently registered in China also for clinical development.
|Relapsed or Refractory Acute Myeloid Leukaemia (AML) or Higher Risk Myelodysplastic Syndrome (MDS)
|This Phase I/Ib clinical trial is of a single centre, nonrandomized, investigator‐initiated study design. The safety and tolerability of PRGN‐3006 UltraCAR-T will be evaluated following intravenous administration of escalating doses in subjects with relapsed or refractory AML or higher risk MDS.
|PRGN-3006 utilizes the sponsor's proprietary UltraCAR-T therapeutic platform, which eliminates ex vivo expansion and reduces manufacturing time to less than two days following non-viral gene transfer at the clinical site. PRGN-3006 UltraCAR-T is a multigenic CAR-T cell treatment which applies the sponsor's advanced non-viral gene delivery system to co-express a chimeric antigen receptor, membrane-bound interleukin‐15 (mbIL15), and a kill switch mechanism for more precise and controlled targeting in relapsed or refractory AML and higher risk MDS. The clinical trial is being perfromed in collaboration with the Moffitt Cancer Center.
|SX-682 in combination with KEYTRUDA® (Pembrolizumab)
|This Phase I/II clinical trial is an open-label study which will assess the safety, tolerability, immune response markers, and overall response rates achieved with SX-682 in combination with KEYTRUDA® in up to 77 subjects with metastatic melanoma. The study will assess biomarkers identified from paired biopsies taken before and after the three-weeks of monotherapy and combination treatments, as well as clinical outcomes observed over the course of the trial. The trial is being carried out at the Massachusetts General Hospital and Dana-Farber Cancer Institute.
|From preclinical studies, SX-682 demonstrated that it enhances both PD-1 immune checkpoint inhibition and T cell receptor engineered T cell elicitation. Effects include a reduction of myelosuppressive cells in the tumour microenvironment and augmentation of NK and T cell infiltration into the tumour site. Clinical studies to date have revealed an inverse correlation between heamatological CXCR1/2 ligands and survival of subjects treated with anti-PD1 therapy.
|Mitochondrial Augmentation Therapy (MAT)
|This Phase I/II clinical trial is of an open label, single dose study design to assess the safety and therapeutic effects of transplantation of MNV-BM-BLD, the sponsor’s autologous CD34+ cells enriched with blood-derived mitochondria, in paediatric subjects. The study will recruit a total of seven patients by invitation and the primary outcome will be safety as determined by the number of participants with treatment-related adverse events at one year duration, as well as quality of life improvement as determined by an International Paediatric Mitochondrial Disease Scale (IPMDS), a multi-dimensional scale rating clinically relevant aspects of mitochondrial disease in children.
|The secondary outcomes measured also at one year duration will include cognitive status, changes in brain MRI, changes in physical activity and muscle function, changes in body mass, and changes in peripheral blood lactate levels. As per study protocol, autologous CD34+ cells enriched with blood-derived mitochondria manufactured by the sponsor’s proprietary MAT platform will be transplanted via a single dose into paediatric subjects with Pearson syndrome to increase the levels of normal mitochondrial DNA. Pearson syndrome is a debilitating genetic disorder caused by a deletion in the mitochondrial DNA and affects approximately 100 child cases globally. Such deletions cause cellular respiration dysfunction, leading to poor energy production in affected patients. Pearson syndrome affects many parts of the body but in particular bone marrow cells and the pancreas.
|Xeris Pharmaceuticals, Inc.
|Developmental Ready-to-Use Glucagon
|Post-Bariatric Hypoglycaemia (PBH) following Bariatric Surgery
|This Phase II clinical trial, is of a randomized, placebo-controlled, double-blind study design which will assess the efficacy, safety and tolerability of the sponsor's ready-to-use glucagon in treating symptomatic postprandial hypoglycaemia among 12 patients with PBH initially during two in-patient clinical research centre visits, and then ongoing as part of a 12-week outpatient phase. Efficacy will be determined during confirmed hypoglycaemic episodes by plasma glucose recovery (blood glucose >70 mg/dL) at 15 minutes after dosing with ready-to-use glucagon or placebo.
|PBH is a complication of bariatric surgery considered to be related to excessive insulin secretion in response to a meal. The onset of PBH can begin one to eight years after gastric bypass surgery. Glucagon is the standard of care for treating severe hypoglycaemia. The sponsor is applying its novel technology platforms to develop and commercialize ready-to-use, room-temperature stable injectable and infusible drug formulations including its ready-to-use glucagon candidate. The sponsor’s proprietary XeriSol™ and XeriJect™ formulation technologies are being evaluated for the subcutaneous (SC) and intramuscular (IM) administration of highly-concentrated, non-aqueous, ready-to-use formulations.
|Pertussis (Whooping Cough)
|This Phase IIb clinical trial is of a multicentre, randomized, placebo-controlled, and observer-blinded study design which will evaluate the immunological response and safety profile of single dose and two dose vaccination adminstration schedules of the BPZE1 vaccination, a live attenuated intranasal pertussis vaccine in healthy adults. Roughly 300 subjects will be randomly assigned 2:1 for the first (primary) vaccination with 200 subjects assigned to BPZE1 vaccination and 100 subjects to Boostrix™ (currently marketed vaccine). Half of the subjects in each primary vaccination group will receive a second (booster) of the BPZE1 vaccination and the other half will receive placebo. The primary immuno-efficacy outcome is the proportion of subjects who achieve seroconversion against at least 1 pertussis antigen in nasal secretions on Day 29 or 113 (primary or primary + booster). The primary safety outcomes are solicited adverse events for 7 days after each vaccination and safety laboratory results.
|Key secondary clinical endpoints are systemic immunogenicity (IgG, IgA, and IgG or IgA) including the proportion of subjects that are seropositive to 2 or more pertussis antigens in serum, mucosal immunity including the proportion of subjects generating a seropositive response to 2 or more pertussis antigens in nasal secretions, and the proportion of subjects with BPZE1 nasopharyngeal colonization after the booster vaccination. BPZE1 is designed to vanquish deficiencies of current vaccines, including poor durability and failure to prevent nasopharyngeal Bordetella pertussis infections giving rise to escape mutants and thus transmission to vulnerable infants. Pertussis is a life-threatening disease caused by the highly contagious respiratory bacterium Bordetella pertussis. Despite an estimated global vaccination coverage rate of 84%, current vaccines are unable to control epidemics. Moreover, current vaccines do not fully protect infants under the age of 6 months, since multiple immunization injections are needed at 2, 4 and 6 months.
|X4 Pharmaceuticals, Inc.
|Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM)
|This worldwide Phase III 4WHIM clinical trial is of a 52-week, randomized, double-blind, placebo-controlled, multicentre study design which will assess the safety and efficacy of Mavorixafor in genetically confirmed WHIM patients. The study is intending to recruit up to 28 patients in approximately 20 countries, followed by an open-label extension study. The primary efficacy endpoint for the study will compare the level of circulating neutrophils relative to a clinically meaningful threshold (500 cells/µL), in response to Mavorixafor versus placebo measured during multiple 24-hour periods over the duration of 52 weeks.
|The secondary endpoints of the study include infection rates, wart burden, assessments of immune system function and quality of life. Mavorixafor is a potentially new generation, once-daily, oral, small molecule antagonist of the chemokine receptor, CXCR4. Proof of concept in WHIM patients has been shown with significant increases in neutrophil and lymphocyte counts, both critical biomarkers of CXCR4 signaling and immune function. Mavorixafor has been well tolerated in earlier phase clinical trials.
Week 24 June 2019 – 28 June 2019
|Terns Pharmaceuticals, Inc.
|Non-Alcoholic Steatohepatitis (NASH)
|This Phase I clinical trial is of a randomized, double-blind, placebo-controlled study design to evaluate safety, pharmacokinetics, and plasma biomarkers of the FXR pathway activation in subjects receiving placebo or TERN-101 at various dose levels for 7 days.
|TERN-101 was actually discovered and developed by Eli Lilly and Company and has previously advanced through a Phase I study showing clinical pharmacokinetic properties consistent with once daily dosing. Last year the sponsor, announced a global, exclusive agreement with Eli Lilly to develop, manufacture, and commercialize TERN-101 for the treatment of NASH. TERN-101 is a potent non-bile acid FXR agonist being developed as a therapy for NASH.
|Advanced Solid Tumours
|This Phase I study is being conducted exclusively at University of Colorado Cancer Center enrolling patients with solid tumours for whom no standard therapy exists, to investigate drug safety, tolerability, and dosing of the anti-cancer candidate OKI-179.
|OKI-179 is a strongly selective inhibitor of Class I histone deacetylases (HDACs), a class of enzymes implicated in the development and growth of a range of solid and haematologic cancers. The compound is an analog of the naturally occurring chemical largazole, named after Key Largo, in Florida, US where largazole is bio-synthesised by a class of coral-colonising bacteria indigenous to the region.
|Purdue Pharma, L.P.
|This is a Phase I clinical trial investigating the pharmacokinetic and pharmacodynamic responses to various formulations of Nalmefene Hydrochloride (HCl). The initial stage of this study will compare pharmacokinetic profiles from healthy adult male and female subjects following administration of Nalmefene HCl intramuscularly and intravenously at various doses.
|Nalmefene HCl has a longer duration of action than another opioid antagonist approved medicine named Naloxone, currently administered to block and reverse the effects of opioid drug overdosing.
|Goldfinch Bio, Inc.
|Progressive Kidney Disease (Focal Segmental Glomerulosclerosis (FSGS), Treatment-resistant Minimal Change Disease (TR-MCD) and Diabetic Nephropathy (DN)
|This Phase I trial will investigate the safety, tolerability, and pharmacokinetic profile of GFB-887 in healthy volunteers and in patients with progressive kidney disease. The study will be conducted in two parts. The initial part of the study will be a single-ascending dose escalation component and a food effect component in healthy volunteers, and then the second component of the study, will be a multiple ascending dose component in healthy volunteers. This Phase I trial will also include a study in renally-impaired patients. The primary objectives of the study will be evaluating the safety, tolerability and pharmacokinetic (PK) profile of single and multiple doses of GFB-887.
|The secondary objectives of the study will be evaluating the safety, tolerability and PK of GFB-887 in patients with renal impairment. GFB-887 is a sub-type selective, small molecule TRPC5 ion channel inhibitor in clinical development for the treatment of kidney diseases, namely FSGS, TR-MCD and DN. TRPC5 is a calcium-permeable ion channel, a critical modulator in the pathogenesis of kidney disease. Recent studies have shown that TRPC5 and Rac1, in tandem critically regulate cellular motility, thus leading to a vicious cycle that drives pathogenic remodeling of the actin cytoskeleton in podocytes. This leads to podocyte degradation and consequently breaking the filtration barrier, which ultimately causes proteinuria, the onset of progressive kidney diseases such as FSGS, TR-MCD and DN. By inhibiting TRPC5 as a therapeutic target, offers a potential strategy to restore podocyte integrity and prevent progression of these diseases.
|Aerpio Pharmaceuticals, Inc.
|Primary Open Angle Glaucoma (POAG)
|This Phase I trial is of a double-masked, multiple-ascending dose design recruiting four cohorts of 12 subjects. Each subject will be administered increasing daily doses of a topical ocular formulation of AKB-9778 or placebo over a seven day period. The primary endpoint of the study is ocular safety and tolerability, with intraocular pressure (IOP) lowering as the key pharmacodynamic endpoint.
|The sponsor has recently published research from pre-clinical studies demonstrating that topical ocular dosing of AKB-9778 lowers IOP via its action on the Schlemms canal (a conventional outflow pathway, consisting of the trabecular meshwork that controls IOP), and in two sequential Phase II clinical studies, showed that subcutaneous dosing of AKB-9778 significantly reduced IOP in ocular normotensive patients. For this trial, the sponsor's lead compound, AKB-9778, is being investigated, in a topical drop formulation, for its potential as a treatment for POAG.
|Type 1 Diabetes
|This Phase Ib trial is of a randomized, double-blind, active-controlled, 2 period cross-over design, whereby 24 patients with type 1 diabetes will receive multiple daily doses of ADO09 and its comparator Novolog® (a prandial insulin analog known generically as Insulin Aspart, licensed by Novo Nordisk) over two periods of 24 days each (including 4 days in the clinic and 20 outpatient days), following a run-in period to optimize basal insulin regimen. Patients will receive a continuous glucose monitoring (CGM) system for glucose monitoring and control, as well for the purpose of safety and efficacy assessment throughout the study participation. The primary endpoint is to compare post-meal glucose profiles after bolus injections of ADO09 and Novolog®, injected immediately before a standardized mixed meal, at the end of a 24-day multiple daily injection treatment period.
|Also the clinical trial will assess the safety and efficacy of ADO09 in an outpatient setting, as well as plasma glucose control as monitored by CGM at Days 1-3 and Days 21-23 and pharmacokinetic, pharmacodynamic and gastric emptying profiles of both treatments at the beginning and end of the trial. Not only is insulin lacking in the type I diabetic, but so is amylin. Amylin modulates glucose appearance in the blood by inhibiting glucagon thereby suppressing liver glycogenolysis as well as inducing satiety by reducing gastric emptying. As the diabetes progresses, and panacreatic beta cell mass disintegrates, this leads eventually to a shutdown of both insulin and amylin secretion. The sponsor's proprietary ADO09 formulation enables the fixed-ratio combination of the FDA-approved amylin analogue pramlintide and A21G human insulin analog (A21G human insulin) with the intention of deriving superior postprandial glycaemic control without the clinical and patient burden of separate injections of two different therapies.
|Tolero Pharmaceuticals, Inc.
|Previously Treated Chronic Lymphocytic Leukaemia (CLL) and Small Lymphocytic Lymphoma (SLL)
|In both Phases I and II of this study, patients will be assigned to one of two defined patient cohorts. Patients in the first of these cohorts, will include those who are intolerant to or have progressed to being on B-cell receptor antagonists and/or BCL-2 antagonists therapy, will receive TP-0903 monotherapy. Patients in the other cohort, which will include those who have progression of disease on Ibrutinib and the healthcare provider considers continuation of Ibrutinib therapy to be in the best interest of the patient, will receive a combination therapy of TP-0903 and Ibrutinib. For Phase I of this clinical trial, the primary outcomes are to determine dose-limiting toxicities and the incidence of treatment-emergent adverse events of oral TP-0903 administered once daily for 28 days in patients with previously treated CLL/SLL. For Phase II of this clinical trial, the primary outcome will be to determine the objective response rate according to guidelines set forth by the 2018 International Workshop on CLL. A recommended Phase II dose will be established in Phase I of this clinical trial.
|Secondary outcomes of the Phase I trial will be pertinent to patient pharmocokinetic profiles. For the Phase II of the trial, the secondary outcomes will be assessment of duration of response and overall survival rate. TP-0903 is an investigational oral AXL receptor tyrosine kinase (RTK) inhibitor. AXL belongs to a family of TAM receptor tyrosine kinases (Tyro3, AXL and Mer) and is overexpressed in many human cancers. It has several adverse key functions, namely tumour cell proliferation, tumour cell survival, metastasis, cellular adhesion and aversion of an immune response.
|Pharming Group N.V.
|RUCONEST® (Recombinant Human C1 Esterase Inhibitor (rhC1INH))
|In the initial stage of this Phase I/II trial, the study design will be open label to investigate tolerability and safety of treatment with RUCONEST®. Patient inclusion criteria for this part of the study will be patients mid- to late-stage symptomatic pre-eclampsia, where subjects at their 27 weeks' term or later may receive RUCONEST® from their first clear symptoms of PE for the remainder of their pregnancy. Throughout this period, patients will be constantly monitored to ensure their safety and that of the fetus. For the second stage of the study, it will still remain as open label, but will advance to being a proof of concept investigation following approval by the ethics committees. The patient recruitment planned for this stage will include a total of 30 patients enrolled between two clinical sites, one in the Netherlands and the other in Australia. Patient inclusion criteria for this stage will be mild to moderate pre-eclamptic symptoms at 27 to 34 weeks of pregnancy. Patients will receive only those doses of RUCONEST® already known to be safe from the first stage of the study. The second stage of the study will also assess RUCONEST® against historical documented standard-of-care cases in similar patients.
|The rationale behind the development of RUCONEST® for PE, is the key complement C1 esterase inhibitor (C1INH) of the complement system is the only natural inhibitory mechanism of that system. Pregnant women and PE women have reduced circulating C1INH levels. Acutely affected PE patients have significantly-reduced C1INH levels and therefore by supplying additional rhC1INH to such patients, it is proposed that the rate of progress of PE can be slowed down and thereby reduce the level of damage that it can cause to mother and the unborn baby.
|Noveome Biotherapeutics, Inc.
|Persistent Corneal Epithelial Defects (PEDs)
|This Phase II clinical trial is of an open label, multi-centre design which will assess the safety and efficacy of topical delivery of ST266 in patients with PEDs. The primary endpoint of the study will be to complete healing as determined by fluorescein dye after 28 days of therapy. Each subject will receive a total of 4 doses per day of ST266 over the course of 28 days within the study period.
|ST266 is a cell-free platform biological material comprising hundreds of proteins and other factors involved in cellular healing, protection of the brain and nerves, and modulation of inflammation. The components of ST266 are secreted by a novel population of cells generated by a proprietary protocol of culturing amnion-derived epithelial cells collected from full term placentas, which are normally discarded after childbirth. As reported in preclinical studies, the biological material contains physiological levels of multiple growth factors and cytokines and thus in the clinical setting it is postulated to stimulate certain beneficial anti-inflammatory and neuroprotective responses..
Week 10 June 2019 – 14 June 2019
|Inovio and CEPI
|This Phase I study of placebo-controlled, blinded, dose-escalation design as well as the entire INO-4500 programme will be fully funded through a global partnership with Coalition for Epidemic Preparedness Innovations (CEPI). The sponsor intends to recruit approximately 60 volunteers to evaluate the safety, tolerability and immune responses of INO-4500.
|The sponsor has published findings that this DNA candidate vaccine against Lassa fever provided 100% protection in a pre-clinical study with primates challenged with a lethal dose of the Lassa virus. In a recent press release published by the sponsor it was reported that their "synthetic nucleic acid platform of immunotherapies and vaccines deliver optimized synthetic antigen genes into cells with CELLECTRA® immune enhancing systems, where they are translated into protein antigens that activate an individual's immune system to generate robust targeted T cell and antibody responses."
|COM701 in combination with Opdivo® (Nivolumab)
|Advanced Solid Tumours
|This is Phase I clinical trial, combining escalating doses of COM701 with a fixed dose of Opdivo® (Nivolumab) in patients with advanced solid tumours. The combination dose escalation arm was initiated following the evaluation of well-tolerated doses with no dose-limiting toxicities reported of COM701 from the monotherapy dose escalation arm of the trial. Bristol-Myers Squibb will provide the Opdivo® therapy, a PD-1 inhibitor, for the combination arms of the Phase I study. The primary endpoints of this Phase I trial are safety and tolerability.
|The secondary endpoints of this study include preliminary anti-tumour activity, pharmacokinetics and pharmacodynamics. The trial will also evaluate evidence of preliminary antitumour activity of COM701 as monotherapy as well as in combination with Opdivo® in patients with selected tumour types, including non-small cell lung cancer, ovarian cancer, breast cancer and endometrial cancer. It is expected that the sponsor will recruit approximately 140 patients across the US. COM701 is a first-in-class therapeutic antibody targeting Poliovirus Receptor-related Immunoglobulin (PVRIG), a novel immune checkpoint target candidate discovered computationally by the sponsor.
|Atriva Therapeutics GmbH
|This randomized, double blind dose escalation Phase I trial, is currently ongoing in Belgium. It will assess the safety and tolerability of ATR-002 in 60 healthy volunteers, randomized into three arms. According to the sponsor's Web site, this study will evaluate the safety and pharmacokinetic profile of ATR-002.
|In their recently published press release, the sponsor stated that: "Preclinical data showed that an oral application of ATR-002 leads to the rapid and long-lasting inhibition of the Raf/MEK/ERK pathway and consequently, inhibition of reproduction of virus particles in the body. Compared to standard of care, absence of resistance formation and a longer treatment window were observed."
|Axovant Gene Therapies, Ltd.
|AXO-AAV-GM1 (or AAV9-GLB1)
|On May 16 last month, the sponsor announced the dosing of its first patient in a Phase I clinical study of AXO-AAV-GM1 (also known as AAV9-GLB1), an investigational gene therapy for the treatment of GM1 gangliosidosis. The endpoints of this clinical trial will include safety, biomarker, neurodevelopment, Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) evaluations.
|AXO-AAV-GM1 transports a functional copy of the GLB1 gene through an adeno-associated viral (AAV) vector, with the aim of regaining β-galactosidase enzyme activity for the treatment of GM1 gangliosidosis. The gene therapy is administered intravenously, which has the capacity to widely transduce the central nervous system and cure peripheral manifestations of the disease as well. Preclinical investigations in mice and a naturally-occurring feline model of GM1 gangliosidosis have supported AXO-AAV-GM1’s ability to enhance β-galactosidase enzyme activity, decrease GM1 ganglioside accumulation, ameliorate neuromuscular function, and prolong survival.
|Dicerna Pharmaceuticals, Inc.
|Chronic Hepatitis B Virus (HBV) Infection in Adults
|This Phase I clinical trial (DCR-HBVS-101), is of a randomized, placebo-controlled design to evaluate the safety and tolerability of DCR-HBVS in healthy volunteers and in patients with non-cirrhotic chronic HBV infection. As part of the study design, DCR-HBVS-101 will be divided into three groups/arms: In Group A, 30 HVs are to receive a single ascending-dose of DCR-HBVS (0.1, 1.5, 3, 6, or 12 mg/kg) or placebo, with a four-week follow-up period. Group B is a single-dose arm in which eight participants with HBV who are naïve to nucleoside analog therapy will receive a 3 mg/kg dose of DCR-HBVS or placebo; these participants will be followed for at least 12 weeks. The sponsor anticipates to initiate Group B dosing in the third quarter of 2019, in parallel with Group C at the 3 mg/kg dose level. Group C is a multiple ascending dose arm in which DCR-HBVS (1.5, 3, or 6 mg/kg) or placebo will be administered to 18 participants with HBV who are already being treated with nucleoside analogs, with a treatment and follow-up period of 16 weeks or more. The first participant dosed was from this group, at a dose of 1.5 mg/kg. Study participants in Groups B and C, in whom HBsAg will have dropped by more than 1 log10 IU/mL below baseline at their last scheduled study visit, will continue to be followed until their HBsAg level is less than 1 log10 IU/mL below the baseline value.
|The secondary objectives of this study are to characterize the pharmacokinetic profile of DCR-HBVS and to evaluate preliminary pharmacodynamics and antiviral efficacy on plasma levels of hepatitis B surface antigen (HBsAg) and HBV DNA in blood. DCR-HBVS is composed of a single GalXC molecule that targets HBV messenger RNAs within the HBsAg gene sequence region. Preclinical studies with a standard mouse model of HBV infection demonstrated DCR-HBVS to yield greater than 99% reduction in circulating HBsAg, suggesting a level of HBsAg suppression (both in magnitude and duration of suppression) that may be greater than that achieved from targeting within the X gene sequence region.
|NeuClone Pharmaceuticals, Ltd.
|Moderate to Severe Plaque Psoriasis in Adults and Children 12 years or Older, Active Psoriatic Arthritis and Moderate to Severe Crohn’s Disease in Adults
|This Phase I study is of a three-arm, randomised, double-blind, single-dose design with the primary objective to compare the pharmacokinetics and safety of NeuLara, the sponsor's Stelara® (ustekinumab) biosimilar to US- and EU-sourced Stelara® in healthy volunteers. This multicentre clinical trial of NeuLara will be performed in Australia under the Clinical Trial Notification (CTN) scheme of the Therapeutic Goods Administration (TGA).
|The Stelara® biosimilar NeuLara was developed at the sponsor's facilities from its proprietary NeuMAX® technology and Right from the Start™ development approach. Stelara® (Ustekinumab) is a human monoclonal antibody approved for treatment of moderate to severe plaque psoriasis in adults and children 12 years or older. It is also approved to treat active psoriatic arthritis and moderate to severe Crohn's disease in adults. The efficacy of Stelara® (Ustekinumab) is directed against the inflammatory marker proteins interleukin-12 and -23, that regulate the immune system and immune-mediated inflammatory diseases.
|This Phase II study will investigate the use of 89Zr-Df-IAB22M2C a first in class imaging agent that visualizes the immune system using non-invasive, whole-body in vivo PET imaging of CD8 T cells, to image CD8 T cells prior to (baseline) and after (on-treatment) of cancer patients undergoing immunotherapy-based treatment.
|This clinical trial will recruit metastatic cancer patients and will evaluate the correlation of imaging signals observed using ImaginAb's CD8 T-cell ImmunoPET imaging agent, standard-of-care scans, and immunohistochemistry analysis of CD8 in biopsied tissues. The study will also monitor changes in CD8+ T-cell distribution before and after immuno-oncology therapies.
|IO102 in Combination with KEYTRUDA® (Pembrolizumab)
|Metastatic Non-Small Cell Lung Cancer (NSCLC)
|Last month 15 May, the sponsor announced it has initiated the Phase II portion of a Phase I/II global, open-label, randomized clinical trial studying the investigational candidate IO102 in combination with KEYTRUDA® (Pembrolizumab) for the treatment of first-line patients with metastatic non-small cell lung cancer (NSCLC), the IO102-012/KEYNOTE-764 clinical trial. This is a global clinical trial anticipated to enrol 96 patients across more than 20 sites in the US and Europe
|IO102, is an Indoleamine 2,3-dioxygenase (IDO) derived immune modulating candidate with a dual mechanism of action - annihilating both cancer cells and immune-suppressive cells. The sponsor's IDO-derived immune modulating therapies previously showed both a favourable safety profile and potential for anti-tumour activity in its first human clinical trial of heavily pre-treated patients with NSCLC.
|Idiopathic Pulmonary Fibrosis (IPF)
|In this Phase IIb clinical trial (SCENIC trial), three different doses of RVT-1601 will be compared to placebo after 12 weeks of dosing. The objective primary endpoint of the study is the change in 24-hour cough frequency vs. placebo as measured by a cough monitor. It is a mult-centre trial being conducted at clinical sites in the U.S., Canada, and Europe and is anticipated to enrol up to 180 patients.
|The secondary endpoints of this Phase IIb study include patient reported outcomes such as change in cough-related quality of life and cough severity. Following the double-blind treatment period, all enrolled patients will participate in a 12-week open-label treatment period on RVT-1601. In the Phase IIa portion of the clinical trial of 24 patients with IPF cough, the sponsor reported RVT-1601 to be "well tolerated and produced a statistically significant and clinically meaningful reduction in cough frequency". RVT-1601 is a proprietary inhaled formulation of a mast cell stabilizer with pleiotropic immune modulating activity delivered directly to the lungs via a proprietary electronic nebulizer device, the investigational PARI eFlow®. Distribution of RVT-1601 directly to the lung tissue of pulmonary fibrosis patients has potential for treating IPF cough as well as management of the underlying disease. The RVT-1601 mode of action is via inhibition of inflammatory mediators that contribute to cough and to the progression of fibrosis.
|Rigel Pharmaceuticals, Inc.
|Fostamatinib Disodium Hexahydrate (Fostamatinib)
|Warm Antibody Autoimmune Haemolytic Anaemia (AIHA)
|This Phase III study of Fostamatinib is a placebo-controlled trial of roughly 80 patients to be enrolled with primary or secondary warm AIHA who have failed at least one prior treatment. The primary endpoint will be a durable haemoglobin response by week 24, defined as Hgb > 10 g/dL and > 2 g/dL greater than baseline and a durability of response measure, with the response not being attributed to rescue therapy. Enrollment is expected to take approximately 12 months.
|Presently Fostamatinib is commercially available in the U.S. under the brand name TAVALISSE® (Fostamatinib Disodium Hexahydrate), which is the first and only spleen tyrosine kinase (SYK) inhibitor indicated for the treatment of thrombocytopenia in adult patients with chronic ITP who have had an insufficient response to a previous treatment. AIHA is a rare, debilitating blood disorder in which the immune system produces antibodies that result in the annihilation of the body's own red blood cells. Currently there are no disease-targeted medicines approved for AIHA.
Week 27 May 2019 – 31 May 2019
|Tolero Pharmaceuticals, Inc.
|Advanced Solid Tumours
|This Phase I open-label, dose-escalation, safety, pharmacokinetics (PK), and pharmacodynamic (PD) trial will investigate the dose-limiting toxicities and clinical activity of oral TP-3654 administered in patients with advanced solid tumours. The primary objective of this study is to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of orally administered TP-3654 in patients with advanced solid tumours.
|Secondary objectives of this trial are to evaluate the PK and PD of TP-3654, observe patients for any evidence of antitumour activity of TP-3654 by objective radiographic assessment, and to establish the recommended Phase II dose for future studies with TP-3654. TP-3654 is an investigational second-generation selective PIM kinase inhibitor. PIM kinases are major effectors of JAK/STAT proliferative signaling downstream of multiple growth factors and cytokines. PIM-1 is overexpressed in cancers and is postulated to enhance the ability of fibroblasts to differentiate into myofibroblasts.
|Tempest Therapeutics Inc.
|Advanced Solid Tumour Malignancies
|This Phase I/Ib open-label, dose-escalation and dose-expansion study will evaluate TPST-1120 as a twice-daily oral monotherapy and in combination with marketed cancer drugs such as PD-1 inhibitors, anti-EGFR antibodies or chemotherapy. The primary outcome measures of the study include assessing safety and tolerability and establishing a dose range for expanded studies at specified TPST-1120 doses.
|The secondary outcomes will evaluate the pharmacokinetics, mechanism-based biomarkers and objective response rate. TPST-1120 exhibits its potent anti-tumour effects through direct binding of the PPAR alpha transcription factor, inhibiting the expression of its regulated genes that are critical for fatty acid oxidation. Several malignancies such as hepatocellular carcinoma and renal cell cancer are dependent on fatty acid oxidation.
|ORIC-101 in combination with Nab-Paclitaxel
|Advanced Solid Tumour
|This Phase Ib trial is a dose finding, multi-centre, open label trial designed to determine the safety, pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of ORIC-101 combined with Nab-Paclitaxel in patients with advanced solid tumours. The primary outcome measure for this study is Recommended Phase II Dose (RP2D) over a 12 month timeframe. The RP2D will be as determined by a 3+3 dose escalation design.
|Secondary outcomes will evaluate safety, PK, PD, and preliminary antitumour activity of ORIC-101. The sponsor also plans to initiate additional Phase Ib studies of ORIC-101 in combination with other anti-cancer agents, including with androgen receptor modulators in patients with advanced prostate cancer and with immunotherapy agents. ORIC-101 is a small molecule GR antagonist under clinical development as a therapy for solid tumour malignancies. Mechanistically, ORIC-101 halts GR transcriptional activity and inhibits the pro-survival signals mediated by the activated nuclear receptor.
|ANCA-associated vasculitis (AAV)
|The main objective of this randomized, double-blind, placebo-controlled Phase II study will be to evaluate the efficacy and safety of IFX-1 in patients with moderate to severe AAV. The study plans to recruit approximately 80 patients from roughly 60 sites in up to 12 European countries and Russia. This clinical trial will be conducted in two parts. In Part 1, patients will be randomized to receive either IFX-1 plus a reduced dose of glucocorticoids, or placebo plus a standard dose of glucocorticoids. Patients in both arms will receive the standard of care dosing of immunosuppressive therapy (Rituximab or Cyclophosphamide). Prior to commencing Part 2 of the study, an independent data monitoring committee will evaluate the efficacy and safety results from Part 1 and recommend if the study should continue. Part 2 will evaluate if treatment with IFX-1 alone is as effective as IFX-1 in combination with glucocorticoids. Thus, in Part 2 patients will be randomized to receive IFX-1 plus placebo glucocorticoids versus placebo plus a standard dose of glucocorticoids. Study subjects in both arms will receive standard of care immunosuppressive therapy (Rituximab or Cyclophosphamide).
|The primary endpoint of the study is a 50% reduction in Birmingham Vasculitis Activity Score (BVAS) at week 16, a standard endpoint that has been used in the previous AAV studies. Secondary efficacy endpoints being analyzed include clinical remission, evaluation of the Vasculitis Damage Index, reduction of glucocorticoid toxicity, several relevant biomarkers such as glomerular filtration rate, and patient reported outcomes. IFX-1 is a first-in-class monoclonal anti-human complement factor C5a antibody, which blocks the biological activity of C5a in a potent and effective manner and demonstrates high selectivity towards its target in human blood. Thus, IFX-1 leaves the formation of the membrane attack complex (C5b-9) intact as an important defense mechanism, which is not the case for molecules blocking the cleavage of C5. IFX-1 has been demonstrated to control the inflammatory response driven tissue and organ damage by specifically blocking C5a as a key “amplifier” of this response in pre-clinical studies.
|Rigel Pharmaceuticals, Inc.
|Fostamatinib Disodium Hexahydrate (Fostamatinib)
|Warm Antibody Autoimmune Haemolytic Anaemia (wAIHA)
|This Phase III study of Fostamatinib is a placebo-controlled study of roughly 80 patients with primary or secondary wAIHA who have failed at least one prior treatment. The primary endpoint will be a durable hemoglobin response by week 24, defined as Hgb > 10 g/dL and > 2 g/dL greater than baseline and a durability of response measure, with the response not being attributed to rescue therapy. Patient recruitment is expected to take approximately 12 months. The primary objective of this trial will be to evaluate the efficacy of Fostamatinib in subjects with wAIHA.
|This is the sponsor's first FDA approved product branded as TAVALISSE® (Fostamatinib Disodium Hexahydrate), the only oral spleen tyrosine kinase (SYK) inhibitor, for the treatment of adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment. This clinical trial program represents a Phase III study of TAVALISSE® for treatment of wAIHA. AIHA is a rare, serious blood disorder in which the immune system produces antibodies that result in the destruction of the body's own red blood cells. AIHA caused by warm autoantibodies (wAIHA), ie, antibodies that react with their antigens on the red blood cell optimally at 37°C, is the most common type of AIHA, causing approximately 70% to 80% of all adult cases
|RGN-259 Eye Drops
|Dry Eye Syndrome (DES)
|This Phase III study will evaluate RGN-259, a sterile, preservative-free eye drop in 700 patients with DES at roughly fifteen nationwide clinical sites across the U.S., including hospitals and clinics specializing in ophthalmology, comparing the drug candidate to placebo. The objective of this study is to compare the safety and efficacy of RGN-259 ophthalmic solution to placebo for the treatment of the signs and symptoms of DES. Study subjects will be randomized in a 1:1 ratio of RGN-259 to placebo ophthalmic solution.
|DES pathology is due to the loss of homeostasis of the tear film resulting in pain, itching, blurry vision, and dryness, among other symptoms. RGN-259 eye drops contain an active small protein, thymosin beta 4, which is naturally occurring in tears and other body fluids.
Week 20 May 2019 – 24 May 2019
|Advanced Solid Tumours
|This is a Phase I study (DUET-3) of multiple-dose, dose-escalation design that will evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary anti-tumour activity of intravenous administration of XmAb23104 in patients with selected advanced solid tumours.
|XmAb23104 is an antibody of dual specificity that simultaneously targets PD-1, an immune checkpoint receptor, and ICOS, an immune co-stimulatory receptor, and is designed to promote tumour-selective T-cell activation. Xencor’s XmAb® bispecific Fc domain serves as the scaffold for these two antigen binding domains and provides long circulating half-life, stability and ease of manufacture. XmAb bispecific Fc domains have been engineered to eliminate Fc gamma receptor (FcγR) binding, with the intent to prevent activation and/or depletion of T cells via interaction from FcγR-expressing cells.
|Shattuck Labs, Inc.
|Advanced Solid Tumours and Lymphomas
|This is a dose escalation Phase I study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamic, and anti-tumour activity of SL-279252 in patients with advanced solid tumours or lymphomas. This is a multi-centre, global trial.
|SL-279252 is a novel therapeutic derived from the sponsor's proprietary Agonist Redirected Checkpoint (ARC™) platform and represents its first-in-human clinical trial. The dual-sided nature of SL-279252 is designed to simultaneously block the PD-L1 inhibitory signal and stimulate OX40 signaling. Preclinical studies have demonstrated that SL-279252 potently stimulates anti-tumour T cell activity.
|Alzheimer’s Disease (AD)
|Last year 15 November, the sponsor announced the initiation of its INVOKE Phase I study as a randomized, double-blind, placebo-controlled, dose escalation clinical trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of AL002 in healthy volunteers and AD patients. Now this Phase Ib portion of the INVOKE clinical study will assess the safety of multiple doses and measure target-specific biomarker changes related to AL002 in plasma and in cerebrospinal fluid in AD patients.
|AL002 is a monoclonal antibody that targets a triggering receptor expressed on myeloid cells 2 (TREM2) with the strongest genetic links after APOE4 to AD and related neurodegenerative disorders. TREM2 is a transmembrane receptor protein manifested on a subset of innate immune cells and selectively on microglia, which constitute the brain’s immune system. TREM2 is postulated to promote improved cell migration to the site of injury, improved cell survival, increased phagocytosis, and increased cell proliferation. Loss of TREM2 function therefore triggers AD and related dementia pathology and research indicates that enhancing TREM2 levels in the brain may prevent or reduce the severity of neurodegenerative disorders.
Week 13 May 2019 – 17 May 2019
|This is a single-arm, dose-escalation multi-centre Phase Ib study which is recruiting up to 24 patients with primary MF, post-essential thrombocythemia MF, or post-polycythemia vera MF with ≥ grade 2 bone marrow fibrosis. Clinical outcomes include safety, response, clinical and hematological improvement, as well as assessment of the degree of bone marrow fibrosis.
|AVID200’s novel dual mode of action in MF centers around its anti-fibrotic effects and ability to restore hematopoiesis. AVID200 is an isoform-selective and highly potent inhibitor of TGF-beta 1 and 3, the two principal pro-fibrotic TGF-beta isoforms. These TGF-beta isoforms regulate the pathogenesis and progression of fibrotic diseases such as MF.
|Tetra Discovery Partners
|Early Alzheimer’s Disease (AD)
|This PICASSO AD clinical trial is a three-month randomized, double-blind, placebo-controlled mult-centre Phase II study (up to 60 sites) being conducted across the United States. The study will recruit approximately 255 patients, in the age range of 55 to 85 years, with a clinical diagnosis of early AD, and will consist of three parallel study arms to evaluate two twice-daily doses of BPN14770 versus placebo. The primary endpoint for the study will be the change from baseline scores in a standardized clinical assessment of memory (Repeatable Battery for Assessment of Neurological Status - Delayed Memory Index; RBANS-DMI).
|Secondary endpoints will include changes from baseline in a variety of other standardized tests and clinical assessments of memory, cognition, and daily function, as well as pharmacokinetic measurements. BPN14770 is a novel therapeutic agent that selectively inhibits phosphodiesterase-4D (PDE4D) to enhance early and late stages of memory formation. Its unique mechanism of action has the potential to improve cognitive and memory function in chronic CNS disorders including Fragile X Syndrome, AD and other dementias, learning or developmental disabilities and schizophrenia.
|Axovant Gene Therapies, Ltd.
|Parkinson’s Disease (PD)
|The sponsor reported interim results from the first cohort of the SUNRISE-PD Phase II study of AXO-Lenti-PD in PD patients. AXO-Lenti-PD demonstrated that it is generally well-tolerated with no serious adverse events reported at the low dose (4.2 x 106 TU). In addition, consistent improvements over the study period were observed across multiple motor function and dyskinesia scales, including improvements on the UPDRS Part III OFF score of 14-points and 36-points, respectively, in the two patients studied in the low-dose cohort. In the second quarter of 2019, the sponsor plans to proceed to the second cohort of the SUNRISE-PD study, at a higher dose of 1.4 x 107 TU.
|AXO-Lenti-PD is an investigational gene therapy for the treatment of PD that is designed to deliver three genes (tyrosine hydroxylase, cyclohydrolase 1, and aromatic L-amino acid decarboxylase) via a single lentiviral vector to encode a set of critical enzymes required for dopamine synthesis, with the aim of stabilising and restoring steady levels of dopamine in the brain. The investigational gene therapy seeks to provide patient benefit for years following a single administration.
|3-V Biosciences, Inc.
|Non-Alcoholic Steatohepatitis (NASH)
|In this randomized, placebo-controlled Phase II clinical trial, the efficacy of TVB-2640 in roughly 90 NASH patients in the United States and about 25 to 30 NASH patients in China. Inclusion criteria is that the patient will have at least 8% liver fat at baseline, as measured by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF), and evidence of stage F1 to F3 fibrosis. The primary endpoint is the efficacy of TVB-2640 on liver fat reduction, compared to baseline, following 12 weeks of daily, continuous dosing.
|TVB-2640's effect on levels of plasma triglycerides, liver enzymes, inflammatory and fibrotic biomarkers are also secondary outcomes to be evaluated. TVB-2640 is an orally bioavailable, first-in-class inhibitor of fatty acid synthase (FASN). FASN is a key enzyme in the de novo lipogenesis (DNL) pathway that is responsible for the synthesis of excess fat in the liver of patients with NASH.
|Persistent Atrial Fibrillation (AF)
|This Phase II placebo-controlled, double-blind, randomized PROMISE-AF study will evaluate the efficacy, safety, and population pharmacokinetics of OMT-28 in patients with persistent AF. The study is expected to enroll up to 120 patients via clinical centres in four European countries. Three different dose levels of OMT-28 will be administered once daily versus placebo and the drug candidate's impact on the maintenance of normal sinus rhythm in patients with persistent AF. To accurately detect and monitor arrhythmias and assess the AF burden for patients, data will be collected via an implantable cardiac monitor.
|OMT-28 is a stable synthetic small molecule analog of the natural omega-3 fatty acid metabolite 17,18-EEQ, which has a molecular structure optimized to provide high efficacy, safety and oral bioavailability. The drug candidate has already proven its anti-arrhythmic, cardioprotective and anti-fibrotic potential in different in vivo models.
|Cabozantinib (CABOMETYX) in combination with Nivolumab (Opdivo) and Ipilimumab (Yervoy) versus Nivolumab and Ipilimumab
|Previously Untreated Advanced Renal Cell Carcinoma (RCC)
|This is the third pivotal Phase III clinical trial initiated by the sponsor, hence the COSMIC-313 trial will investigate Cabozantinib (CABOMETYX®) in combination with Nivolumab (Opdivo®) and Ipilimumab (Yervoy®) versus Nivolumab and Ipilimumab in patients with previously untreated advanced RCC with intermediate- or poor-risk disease as according to the International Metastatic Renal Cell Carcinoma Database Consortium. This COSMIC-313 trial is of a multicentre, randomized, double-blinded, controlled design seeking to enroll approximately 676 patients at 150 sites globally. Patients will be randomized 1:1 to the experimental arm of Cabozantinib in combination with Nivolumab and Ipilimumab and to the control arm of Nivolumab and Ipilimumab in combination with matched placebo. The primary endpoint of this clinical trial is progression-free survival.
|According to Dr. Gisela Schwab, M.D., President of Product Development and Medical Affairs and Chief Medical Officer of Exelixis “The mechanisms of action of single agent Cabozantinib and the combination of Nivolumab and Ipilimumab are complementary, and each has demonstrated efficacy in advanced renal cell carcinoma. The further combination of these agents as a triplet regimen may offer promise to previously untreated patients with intermediate- or poor-risk disease, who are known to have poor treatment outcomes". The secondary endpoints of this study are overall survival and objective response rate.
|I-Mab Biopharma and MorphoSys AG
|Relapsed or Refractory Multiple Myeloma (MM)
|This randomized, open-label, parallel-controlled, multicentre Phase III study will be conducted in mainland China and Taiwan to evaluate the efficacy and safety of the combination of TJ202/MOR202 plus Lenalidomide and Dexamethasone versus the combination of Lenalidomide and Dexamethasone in patients with relapsed or refractory MM who received at least one prior line of treatment. The primary endpoint is to evaluate the progression-free survival comparing the efficacy of TJ202/MOR202 plus Lenalidomide/Dexamethasone versus Lenalidomide/Dexamethasone alone.
|TJ202/MOR202 is an investigational human monoclonal antibody derived from MorphoSys's HuCAL antibody technology. The antibody is directed against CD38 on the surface of multiple myeloma cells, which has been characterized as one of the most potent and uniformly expressed antigens on the surface of malignant plasma cells. The proposed mechanism of action of the antibody is that it recruits cells of the body's immune system to kill the tumour through antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). The antibody does not involve complement dependent (CDC) cytotoxicity, another type of immune activated mechanism involved in tumour cell killing.
|ACADIA Pharmaceuticals, Inc.
|Major Depressive Disorder (MDD)
|This is a 6-week, parallel-designed, randomized, double-blind, placebo-controlled, multi-centre Phase III study (CLARITY-3) designed to evaluate the efficacy and safety of pimavanserin as AN adjunctive treatment in patients with MDD who have an inadequate response to standard antidepressant therapy with either a selective serotonin reuptake inhibitor (SSRI) or a norepinephrine reuptake inhibitors (SNRI). CLARITY-3 will recruit approximately 280 patients internationally. Patients will be randomized to receive six weeks of oral treatment with either 34 mg of Pimavanserin or placebo, once daily, in addition to their ongoing antidepressant. The primary endpoint is the change from baseline on the 17-item Hamilton Depression Rating Scale (HAMD-17) total score.
|Patients who complete the CLARITY-3 trial will be eligible to participate in a 52-week open-label extension study to evaluate the long-term safety and tolerability of Pimavanserin. Pimavanserin is a selective serotonin inverse agonist selectively targeting 5-HT 2A receptors. Such receptors are considered to play a vital role in depression, psychosis, and other neuropsychiatric disorders.
Week 29 Apr 2019 – 3 May 2019
|On 9 April this month, the sponsor initiated enrollment of patients into a phase I trial of IMA203, its third T-cell receptor (TCR)-transduced adoptive cell therapy program. IMA203 is an investigational immunotherapy which uses the sponsor’s proprietary ACTengine® approach and is based on genetic engineering of the patient’s own T cells to express an exogenous TCR in order to redirect and activate the T cells to treat the solid tumours. These TCRs are targeted to a site on the tumour identified by Immatics’ proprietary XPRESIDENT® target discovery platform. The TCR-transduced T cells are activated and multiplied outside of the body before being infused into the patient. For IMA203, this process requires 5-6 days of manufacturing time. The primary study objective is to assess the safety and tolerability of the ACTengine® approach, and specifically IMA203, in target-positive solid cancer patients.
|Secondary objectives of the study include the evaluation of feasibility, the persistence of T cells in vivo, and the assessment of anti-tumour activity and biomarkers. ACTengine® uses high-avidity and high-specificity exogenous T-cell receptors (TCRs) identified from natural, human T-cell repertoires, which are introduced by viral vectors into patients’ T cells to recognize and kill the tumour cells. The "re-engineered" T cells are then grown up and reinfused back into the patient for treatment.
|Concert Pharmaceuticals, Inc.
|This additional Phase I clinical trial is designed to assess CTP-692’s safety, tolerability and pharmacokinetics in approximately 80 healthy volunteers. The Phase I program overall includes three studies: a crossover comparison of CTP-692 versus D-serine, a single-ascending dose study that also assessed the effect of food on the pharmacokinetics of CTP-692, and this multiple-ascending dose trial. It is of a double-blind, placebo-controlled, multiple-ascending dose study design assessing CTP-692 dosed orally over seven days. with the healthy volunteers treated in the crossover study with both CTP-692 and D-serine, CTP-692 was found to have increased plasma exposure compared to D-serine. In addition, CTP-692 was found to be well tolerated in these subjects and no serious adverse events were reported.
|The candidate drug is a deuterium-modified analog of endogenous D-serine. Based on documented effects of D-serine, the sponsor believes that CTP-692 has the potential to restore NMDA receptor activity in key areas of the brain and improve clinical outcomes in patients with schizophrenia. CTP-692 has demonstrated similar ability to bind to and activate human NMDA receptors relative to D-serine, with the potential for an improved safety profile and improved clinical outcomes in the treatment of schizophrenia.
|National Institutes of Health (NIH)
|In this Phase I study, after injection of H1ssF_3928, participants will record their temperature and any symptoms on a diary card for one week after each injection. They also will be asked to visit the clinic to provide blood samples at various time points. Investigators will test the samples in the laboratory to characterize and measure levels of anti-influenza antibodies. The patients will not be exposed to any influenza virus as part of the clinical trial.
|The candidate vaccine H1ssF_3928 displays part of hemagglutinin (HA), an influenza protein, on the surface of a microscopic nanoparticle made of nonhuman ferritin. Based on published research the sponsors believe the vaccine will allow the body to make protective immune responses against diverse influenza subtypes by focusing the immune system on a portion of the virus that varies relatively little from strain to strain
|On 9 April this month, the sponsor announced the first patient has been enrolled in a clinical trial of NanoDoce (sterile submicron particle docetaxel suspension) for treatment of bladder cancer. This Phase I/II dose-rising study will assess the safety and preliminary efficacy of NanoDoce for patients with high-risk non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC). In a pre-clinical study, NanoDoce administered via intratumoral injection resulted in prolonged, high concentration of the drug in tumour tissue, significant tumour regression, and immune cell infiltration in a xenograft animal model of transitional cell bladder carcinoma.
|Other oncolgy development programs to be initiated by NanOlogy are in peritoneal/ovarian cancers, prostate cancer, pancreatic cancer, pancreatic mucinous cysts, renal cell carcinoma, non-small cell lung cancer, and cutaneous metastases. All NanOlogy INDs are progressing under FDA’s streamlined 505(b)(2) regulatory pathway. NanOlogy represents patented technology whereby the submicron particle production process reduces the size of paclitaxel and docetaxel active pharmaceutical ingredient crystals by up to 400 times into stable submicron particles of pure drug with exponentially increased surface area and unique geometry.
|Provention Bio, Inc.
|Recent Onset Type 1 Diabetes (T1D)
|This PROTECT (PROvention T1D trial Evaluating C-peptide with Teplizumab) Phase III clinical study is a randomized, double‑blind, placebo-controlled, multicentre trial that is anticipated to enroll approximately 300 patients ages 8-17 with recent onset T1D at approximately 80 centers worldwide. The patients will be randomized 2:1 to either two 12-day cycles, six months apart, of intravenous PRV-031 (Teplizumab) or placebo. The primary efficacy endpoint is C-peptide change.
|PRV-031 (Teplizumab) is an anti-CD3 monoclonal antibody (mAb), which is being developed for the interception of type 1 diabetes (T1D). Secondary endpoints include insulin use, HbA1c, hypoglycemic episodes, and safety.
Week 8 Apr 2019 -12 Apr 2019
|Tizona Therapeutics, Inc.
|This Phase I/Ib clinical trial will investigate the safety, tolerability, pharmacokinetics and anti-tumor activity of TTX-030 as a single therapy, in combination with an approved anti-PD-1 immunotherapy, and in combination with standard chemotherapies in adults with advanced cancers.
|TTX-030 is classed as a monoclonal antibody. Its mechanism of action is inhibition of CD39 activity. CD39 is a cell surface enzyme that converts ATP to AMP, the first step in the generation of adenosine in the tumour microenvironment (TME). CD39 is then upregulated on tumours as an immune evasion strategy, and on exhausted T cells and other suppressive cell types. By stopping the activity of CD39, TTX-030 prevents the formation of immune suppressive extracellular adenosine, which otherwise inhibits effector cells in the TME.
|Amylyx Pharmaceuticals, Inc.
|Alzheimer’s Disease (AD)
|This is an expanded Phase II study (PEGASUS) to assess AMX0035 in patients with AD. This PEGASUS clinical trial is of a 3:2 randomized, double-blind, multi-centre, placebo-controlled study design investigating the safety, tolerability and activity of AMX0035 in patients with late mild cognitive impairment or early dementia due to AD over 24 weeks. The study is of a biomarker-based clinical end point seeking to demonstrate the effects of AMX0035 and its potential in treating AD.
|AMX0035 is Amylyx’s proprietary two-drug combination therapy in development to prevent nerve cell death and degeneration. PEGASUS is the first clinical trial of its kind to target both amyloid and tau mechanisms in tandem.
|Odonate Therapeutics, Inc.
|Tesetaxel (in combination with Capecitabine)
|Locally Advanced or Metastatic Breast Cancer (LA/MBC)
|This Phase II study (CONTESSA 2) will assess the combination of Tesetaxel plus a reduced dose of Capecitabine in approximately in 125 patients with locally advanced or metastatic breast cancer (LA/MBC). CONTESSA 2 is of a multinational, multicentre study design investigating orally administered Taxane, in patients with LA/MBC. The study trial will assess tesetaxel dosed orally at 27 mg per metre squared on the first day of each 21-day cycle plus a reduced dose of Capecitabine (1,650 mg/metre-squared/day dosed orally for 14 days of each 21-day cycle) in roughly 125 patients with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor (HR) positive LA/MBC not previously treated with a taxane. The primary endpoint of this study trial will be objective response rate (ORR) as assessed by an Independent Radiologic Review Committee (IRC).
|Tesetaxel is an investigational, orally administered chemotherapy candidate belonging to the taxanes drug class, a commonly used drug class for cancer treatment. Tesetaxel bears several pharmacologic properties making it unique among taxanes, including: oral administration with a low pill dosage burden; an extended ( approx. 8 days) terminal plasma half-life in humans, enabling the maintenance of adequate drug levels with relatively fewer doses; no history of hypersensitivity (allergic) reactions; and significant activity against chemotherapy-resistant tumors. In MBC patients, Tesetaxel was shown to have significant, single-agent antitumor activity in two multicentre, Phase II studies. As a secondary efficacy endpoints, this study will use duration of response (DoR) as assessed by the IRC, progression-free survival (PFS) as assessed by the IRC, disease control rate (DCR) as assessed by the IRC and overall survival (OS).
|Non-Alcoholic Steatohepatitis (NASH)
|This Phase IIa 12 week, multicentre, randomized, double-blind, placebo-controlled, parallel group study will investigate the efficacy and safety of PXL770, a direct adenosine monophosphate-activated protein kinase activator (AMPK), for the treatment of NASH. In this study, three doses of PXL770 versus placebo will be administered to roughly 100 nonalcoholic fatty liver disease (NAFLD) patients who are susceptible to NASH across several clinical sites in the US. The primary endpoint of tthis clinical trial will measure the change in liver fat mass based on magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF), a novel imaging-based biomarker that allows fat mapping of the entire liver. In addition to the Phase IIa study, a separate four-week PK/PD study is expected to be initiated whereby PXL770 will be administered to approximately 32 patients. This study will assess the PK profile of PXL770 in NAFLD patients and its effects on hepatic and metabolic parameters in the target population.
|PXL770 is a first-in-class direct adenosine monophosphate-activated protein kinase (AMPK) activator. AMPK is a central regulator of multiple metabolic pathways leading to the control of lipid metabolism, glucose homeostasis and inflammation. NASH is a metabolic disease with no clear disease origin. It is characterized by the accumulation of fat in the liver causing inflammation and fibrosis. Typical risk factors for NASH include obesity, elevated levels of blood lipids e.g. cholesterol and triglycerides and diabetes.
|Biohaven Pharmaceutical Holding Company, Ltd.
|This Phase II/III, double-blind, randomized, placebo-controlled, dose-ranging study of intranasally administered BHV-3500 will be used to investigate acute treatment of migraine. In this study, 3 doses of BHV-3500 (5, 10 and 20 mg) will be compared to placebo in the treatment of a migraine onset. The planned recruitment of approximately 400 randomized patients per treatment arm, will statistically power the study to provide proof of efficacy on the regulatory endpoints of pain freedom and freedom from the most bothersome migraine-associated symptom at 2 hours post-dose.
|BHV-3500 is a novel, structurally distinct, third-generation calcitonin gene-related peptide (CGRP) receptor antagonist. The study is also designed to detect early onset of other clinical measures that are of great significance to patients, including relief of pain and ability to return to normal functioning.
|Hutchison China MediTech Limited
|Advanced Biliary Tract Cancer (BTC)
|The study is a randomized, open-label, active-control, multi-centre design assessing the effects of Surufatinib (HMPL-012 or Sulfatinib) versus the chemotherapy agent Capecitabine, as a second-line therapy in patients with unresectable or metastatic BTC. The primary endpoint is overall survival (OS).
|Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumour-associated macrophages, promoting the body’s immune response against tumour cells. Secondary outcomes of this clinical trial include measures of tumour control such as progression free survival (“PFS”), objective response rate (ORR), disease control rate (DCR), and duration of response (DOR), quality of life, tumour biomarkers, and safety.
|Patidegib Topical Gel, 2%
|This randomized, double-blind, vehicle-controlled Phase III study will investigate the safety and efficacy of Patidegib Topical Gel 2% applied topically, twice daily to the face over 12 months vs. vehicle gel. Roughly 150 adults with Gorlin Syndrome will be randomized 1:1 to Patidegib topical gel or vehicle. The primary efficacy endpoint of this study will be the number of new surgically eligible BCCs (nSEBs) that develop over the 12-month period in the two treatment arms.
|Patidegib Topical Gel 2%, is an investigational treatment gel designed to reduce the BCC tumour burden in patients with Gorlin Syndrome and High Frequency BCC (HF-BCC) by blocking the disease at its source within the hedgehog signaling pathway. Secondary endpoints of this study will include the total number of new BCCs over 12 months, percentage of study participants developing ≥2 facial nSEBs over 12 months; the percentage of participants developing ≥1 facial nSEBs over 12 months; the number of nSEBs per participant over six and nine months; and change in the Advanced Basal Cell Carcinoma Index (aBCCdex) lesion scale score. An open-label safety and tolerability extension study is planned for at least 12 months for subjects who have completed the Phase III study.
|Aldeyra Therapeutics, Inc.
|Topical Ocular Reproxalap
|Dry Eye Disease
|This Phase III clinical trial (RENEW Trial) is a two-part, multi-centre, randomized, double-masked, parallel-group, vehicle-controlled, adaptive study evaluating the efficacy of reproxalap ophthalmic solution (0.25%) versus vehicle in 400 patients with moderate-to-severe dry eye disease. Initial data from the first part of the study will confirm the dosing regimen and sample size for the second part. The co-primary endpoints of the trial will be ocular dryness and fluorescein nasal region ocular staining in pre-specified moderate to severe patient subsets analyzed over twelve weeks of therapy using Mixed effects Model Repeated Measures (MMRM).
|Last year in September 2018, the sponsor announced results from the Phase IIb dry eye disease study, which demonstrated statistical superiority of Reproxalap versus vehicle across multiple symptoms and signs. In the Phase 2b clinical trial, the MMRM p values for the Phase III co-primary endpoints of dryness and staining were 0.0048 and 0.0007, respectively.
Week 25 Mar 2019 -29 Mar 2019
|Rocket Pharmaceuticals, Inc.
|Fanconi Anaemia (FA)
|This Phase I study is the “Process B” investigation of RP-L102 in two FA paediatric patients at the Center for Definitive and Curative Medicine at Stanford. The “Process B” of RP-L102 incorporates a modified cell enrichment process, transduction enhancers, commercial-grade vector manufacturing and cell processing. The study objective is to evaluate the safety and tolerability of a single infusion of PR-L102, as well as efficacy
|RP-L102 is the spnsor's lentiviral vector (LVV)-based gene therapy in development for patients with FA with collaboration with their European partners at Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) in Spain, CIBER-Rare Diseases and IIS-Fundación Jiménez Díaz. The International Fanconi Anemia Gene Therapy Working Group has assisted in the development of new generation FA gene therapy programs since the inception of a HIV-1-derived, self-inactivating lentiviral vector. RP-L102’s lentiviral vector bears the FANC-A gene as part of the PGK-FANCA-WPRE expression cassette incorporating a phosphoglycerate kinase (PKG) promoter and an optimized woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). The ex-vivo treatment process commences with the removal and isolation of haematopoietic stem cells using a CD34+ selection process. Autologous genetically modified CD34+ enriched haematopoietic cells (fresh or cryopreserved) are infused back into the patient to restore function.
|Infinity Pharmaceuticals, Inc.
|Triple Negative Breast Cancer (TNBC) and Renal Cell Cancer (RCC)
|On 14th March 2019 the sponsor entered into a master clinical supply agreement whereby Roche will supply atezolizumab (Tecentriq®) to the sponsor for use in MARIO-3, a multi-arm combination cohort Phase II clinical trial. The study will investigate IPI-549, as an oral immuno-oncology product candidate targeting immune-suppressive tumour-associated myeloid cells through selective inhibition of phosphoinositide-3-kinase (PI3K)-gamma, in combinations with Tecentriq and Abraxane (nab-paclitaxel) in front-line TNBC patients and in combination with Tecentriq and Avastin (bevacizumab) in front-line RCC patients commencing in the second half of 2019.
|MARIO-1 is an ongoing Phase I/Ib study evaluating IPI-549 as a monotherapy and in combination with Opdivo® (nivolumab) in approximately 225 patients with advanced solid tumours including patients refractory to anti-PD-1 therapy. The sponsor plans to initiate MARIO-275, a global, randomized, combination study of IPI-549 combined with Opdivo in I/O naïve urothelial cancer patients, as well as to initiate MARIO-3, the first IPI-549 combination study in front-line advanced cancer patients.
|Theravance Biopharma, Inc.
|Moderately to Severely Active Ulcerative Colitis (UC)
|This Phase IIb/III clinical trial will be of a multi-centre, randomized, double-blind, multi-dose, placebo-controlled, parallel-group study design to investigate the efficacy, safety and tolerability of induction and maintenance therapy with TD-1473 in patients with moderately to severely active UC. The Phase IIb dose-finding induction arm of the study will examine the effect of eight weeks of treatment with select once-daily doses of TD-1473 on change from baseline in total Mayo score as the primary endpoint and will also investigate rates of clinical response and remission, endoscopic mucosal healing, safety and tolerability. Based on efficacy, safety and tolerability findings from the dose-finding portion of the study, one or more doses of TD-1473 will be screened and evaluated in the Phase III induction arm of the study, with the primary objectives of evaluating clinical remission rates with TD-1473 compared to placebo at week 8 as well as the safety and tolerability profile of TD-1473.
|Patients who achieve clinical responses during the induction stage of the study, either from the Phase IIb or Phase III part of the clinical trial, will then be immediately enrolled in a Phase III maintenance arm of the study. Patients will be randomized to receive placebo or one of two doses of TD-1473 for 44 weeks. The primary objectives of the maintenance study are to assess the clinical remission rates for TD-1473 as compared to placebo after 44 weeks, as well as safety and tolerability of TD-1473. TD-1473 is an internally-discovered JAK inhibitor that has demonstrated a high affinity for each of the JAK family of enzymes. Importantly, TD-1473 is a gut-selective treatment specifically designed to distribute adequately and predominantly to the tissues of the intestinal tract, treating inflammation in those tissues while minimizing its systemic exposure. TD-1473 belongs to a class of JAK inhibitors which function to inhibit the activity of one or more of the Janus kinase family of enzymes (JAK1, JAK2, JAK3, TYK2) that play a key role in cytokine signaling. TD-1473 has demonstrated a high affinity for each of the JAK family of enzymes. As a potential treatment candidate for UC, TD-1473 is a gut-selective treatment specifically designed to distribute adequately and predominantly to the tissues of the intestinal tract, treating inflammation in those tissues while minimizing its systemic exposure.
|Biohaven Pharmaceutical Holding Company Ltd.
|Spinocerebellar Ataxia (SCA)
|This Phase III clinical trial will recruit approximately 230 patients for a study of randomized, double-blind, placebo-controlled design across roughly 22 sites in the U.S. Both the efficacy and safety of troriluzole will be assessed over 48 weeks in patients with a diagnosis of SCA Types 1, 2, 3, 6, 7, 8, and 10. The primary endpoint of the study is the change in a patient's score on the Modified Functional Scale for the Assessment and Rating of Ataxia, a scale designed to evaluate the severity of symptoms in patients with SCA.
|Troriluzole is a 3rd generation new chemical entity that modulates glutamate, the most common excitatory neurotransmitter in human. The primary mechanism of action of this prodrug is reducing synaptic levels of glutamate by raising glutamate uptake from the synapse, thus augmenting expression and function of excitatory amino acid transporters (i.e., EAAT2) located on glial cells that play a main role in clearing glutamate from the synapse.
|Moderate to Severe Chronic Plaque Psoriasis (PP)
|This Phase III clinical trial has the study objective to compare AVT02 and HUMIRA® in terms of safety, efficacy, tolerability and immunogenicity in adult patients with moderate to severe chronic plaque psoriasis. The study will recruit 400 patients across approximately 30 sites in Europe. This AVT02 biosimilar contains a high concentration formulation (100 mg/ml) of adalimumab, which is anticipated to be more convenient for patients based on reduced injection volume. This is a follow up study from the Phase I pharmacokinetic study (AVT02-GL-101) that is currently ongoing in healthy volunteers in Australia and New Zealand.
|Currently HUMIRA® is the leading treatment option for several autoimmune diseases and is not limited to PP treatment. It inhibits the Tumor Necrosis Alpha (TNF-α) involved in systemic inflammation involved in PP. PP is an immune-mediated dermal disorder that causes raised, red, scaly patches to appear on the skin. PP accounts for approximately 80%-90% of psoriasis cases.
|Advanced Non Small Cell Lung Cancer (Advanced NSCLC) and Cachexia
|This Phase III clinical trial comprises of a two 24-week double-blind randomized placebo-controlled multiregional confirmatory study of identical study design for both treatment and placebo arms to evaluate anamorelin for the treatment of weight loss and anorexia in patients with advanced NSCLC with cachexia. The primary efficacy measure will be evaluated at week 9 and will be based on the concomitant occurrence of a clinically relevant improvement of both body weight and a validated PRO (5-item Anorexia Symptoms Scale score) in alive patients at Day 64.
|Anamorelin is a selective ghrelin receptor agonist of oral formulation which activates multiple pathways involved in the positive regulation of appetite and body weight. Cancer cachexia is a multifactorial disorder with symptoms of lost muscle mass and body weight, and is typically accompanied by anorexia or low appetite.
|Santhera Pharmaceuticals AG
|Leber’s Hereditary Optic Neuropathy (LHON)
|On 12th March 2019, the sponsor announced the completion of patient enrollment for its ongoing Phase IV study (LEROS) with Raxone® (idebenone) for the treatment of LHON. LEROS is a Phase IV, external natural history controlled, open-label intervention clinical trial to further assess the efficacy and safety of long-term treatment with Raxone® in patients with LHON. Patients were eligible for study recruitment up to five years after the initial onset of symptoms of vision loss and were stratified according to their time since onset of vision loss to evaluate the influence of disease duration on treatment efficacy. The primary endpoint of the study will be to assess the efficacy of Raxone to improve or stabilize visual acuity (VA) in patients starting treatment up to one year after the onset of vision loss, compared to an external natural history control group.
|The LEROS study follows on from the results of the double-blind, randomized, placebo-controlled RHODOS trial and data from an Expanded Access Program which demonstrated clinically meaningful outcomes of Raxone treatment for patients with LHON. With the enrolment of 197 patients complete, the subjects will be treated with Raxone (150 mg idebenone tablets) at a daily dose of 900 mg for 24 months. The LEROS clinical trial will be conducted at 31 study sites across nine European countries and the USA and the sponsor expects to complete the trial by the 2nd quarter of 2021. LHON is a heritable genetic disorder causing profound vision loss and blindness. Virtually all LHON patients bear one of three pathogenic mutations of the mitochondrial DNA, which leads to a defect in the complex I subunit of the mitochondrial respiratory chain. This defect causes decreased cellular energy (ATP) production, increased reactive oxygen species (ROS) production Raxone (idebenone), is the synthetic short-chain benzoquinone and a cofactor moiety of the enzyme NAD(P)H:quinone oxidoreductase (NQO1), which has demonstrated recovery of visual acuity by circumventing the complex I defect, thus reducing and scavenging ROS, as well as restoring cellular energy levels in retinal ganglion cells.
Week 11 Mar 2019 -15 Mar 2019
|Phoenix Tissue Repair, Inc.
|Recessive Dystrophic Epidermolysis Bullosa (RDEB)
|This Phase I/II clinical study will be recruiting 14 patients who will each be administrated intravenously PTR-01, a protein replacement therapy which uses a recombinant collagen type VII (rC7) for the potential treatment of RDEB over a 10-week period. Primary endpoints of the study are to evaluate the safety, tolerability and pharmacokinetics of PTR-01 in RDEB patients.
|RDEB is a rare genetic multisystem disease manifested with severe skin blistering, and the current treatment approach is limited to palliative symptom management. Preclinical studies of PTR-01 found C7 (whereas in this study a recombinant collagen type VII (rC7) will be used) to be distributed to the basement membrane of the skin, and demonstrated restoration of anchoring fibrils, thus promoting healing.
|Relapsing-Remitting Multiple Sclerosis (RRMS)
|This Phase II clinical trial is of an international, multicenter, double-blind, placebo-controlled, randomized, parallel-group study design. The sponsors are anticipating to recruit approximately 200 patients from more than 40 clinical centres across four European countries. The primary objective of the study is to determine the dose response of 30 mg/day and 45 mg/day of IMU-838, once daily, for the treatment of RRMS based on magnetic resonance imaging (MRI) assessments. Inclusion criteria for the study is that the patient has shown RRMS activity based on clinical evidence of relapse and MRI criteria. The trial includes a blinded 24-week main treatment arm with an optional extended treatment period to evaluate long-term safety and tolerability of IMU-838 that will be unblinded when all patients have completed the main treatment and the study database has been locked. Primary endpoint of the clinical trial is the cumulative number of combined unique active (CUA) MRI lesions, up to week 24.
|IMU-838 is a next-generation selective immune modulator oral therapy whereby the active moiety inhibits the intracellular metabolism of activated immune cells by blocking the dihydroorotate dehydrogenase (DHODH) enzyme. IMU-838 holds specific efficacy on activated T and B cells leaving the other immune cells largely unaffected and thus enables the immune system to carry on fighting infections. Notably IMU-838 did not reveal an increased rate of infections compared to placebo in earlier clinical trials for other indications.
|Debiopharm International SA
|Afabicin (Debio 1450)
|Staphylococcal Bone and Joint Infection (BJI) (NCT03723551)
|This randomized open-label active-controlled Phase II trial will investigate the safety, tolerability, and efficacy of oral or intravenous (IV) Afabicin (Debio 1450) in the treatment of patients with bone or joint infection (BJI) as the primary study objective. This international clinical trial with sites in both Ukraine and the US, in 60 patients seeking to be treated with Afabicin or a comparator drug for up to 12 weeks. The primary endpoints of the trial are safety and tolerability. Improvement of inflammation and microbiological eradication of the baseline pathogen with further assessment likely with secondary endpoints. As an open label study, data will be published as the trial progresses.
|Afabicin (Debio 1450) is a new first-in-class antibiotic candidate available in both oral and IV formulations. Afabicin is a highly potent, staphylococcus-selective antibiotic with little likelihood to develop resistance. As a FabI inhibitor the candidate is active against staphylococci strains which are resistant to the current standard-of-care antibiotics such as beta-lactams, vancomycin, daptomycin or linezolid. Thus Debio 1450 shows potential to tackle such BJIs as a hard-to-treat infection caused by staphylococci.
|Recurrent Vulvo-Vaginal Candidiasis (RVVC)
|The sponsor has already launched patient recruitment in eleven countries for its two VIOLET Phase 3 studies evaluating VT-1161 in RVVC, and on 27th February last month, initiated enrolling patients for their third Phase III ultraVIOLET study. This additional randomized, double-blind ultraVIOLET Phase 3 study will be performed in the U.S. across approximately 45 clinical sites with up to 180 randomized patients. This particular Phase III ultraVIOLET study will investigate the effectiveness and safety of VT-1161 for the treatment of acute VVC episodes in patients with RVVC in two sequential parts. The first part will be a 2-week study for the treatment of the patient's current VVC episode when the patient will take either fluconazole or VT-1161 (according to a random assignment). The second part will consist of 11 week follow-up, whereby the patient will take either VT-1161 or a placebo (according to the random assignment from the first part of the study), and then finally a 37 week follow-up period. The primary endpoint of the study will evaluate the percentage of patients with one or more culture-verified acute VVC episodes over a 50 week time frame.
|VT-1161 is an orally available inhibitor of fungal CYP51 designed to have greater selectivity, fewer side effects and improved potency compared to fluconazole for treatment of RVVC.
Week 25 Feb 2019 -1 Mar 2019
|Ocular Therapeutix, Inc.
|Wet Age-Related Macular Degeneration (AMD)
|This Phase I study is of a multi-centre, open-label design to investgate the safety, durability, and tolerability of OTX-TKI. Administered as an intravitreal injection, this bioresorbable hydrogel fibre implant is formulated with a tyrosine kinase inhibitor and is to be delivered to patients with wet AMD. This trial will assess biological efficacy by measuring retinal thickness using standard optical coherence tomography and monitoring visual acuity over time.
|The candidate drug is formulated with tyrosine kinase inhibitor (TKI) particles suspended in a bioresorbable hydrogel with an injectable fiber that can be delivered through a small-gauge, sterile injection needle to the back of the eye. OTX-TKI is designed to deliver the drug to target tissues for a period of up to nine months, thereby potentially extending the dosing interval from the one month, to a two month frequency needed with the current standard of care. Preclinical data have shown that delivering the TKI particles to the posterior segment of the eye with sustained pharmacokinetic or pharmacodynamic effect for the treatment of VEGF-induced retinal leakage can last up to a duration of twelve months.
|PD-L1 Expressing Tumours
|This is Phase I study will investigate the dose-escalation profile of INBRX-105, a novel, multispecific antibody candidate that in dual mode acts as both an antagonist of PD-L1 and a conditional agonist of 4-1BB in development for the treatment of PD-L1 expressing tumors, including those that are resistant to approved checkpoint inhibitor therapies. This clinical trial seeks to determine the safety profile of INBRX-105 in human subjects, as well as the recommended therapeutic dose level for Phase II studies.
|The INBRX-105 mechanism of action is based on "checkpoint inversion", whereby the therapeutic candidate acts as an adaptor to convert a PD-L1-mediated immune-suppressive signal into an immune-stimulatory response through localized 4-1BB agonism. The drug candidate is a tetravalent bispecific antibody that has been developed using sponsor's proprietary sdAb platform. It is comprised of four binding domains, two targeting PD-L1 and two targeting 4-1BB, however it is roughly one-third smaller in size than a conventional bivalent antibody. The number and positioning of the binding domains within INBRX-105 were designed to allow for potent and sustained PD-L1 blockade, as well as robust and conditional 4-1BB agonism in the presence of PD-L1, a target enriched in the tumour microenvironment and associated lymphoid tissues.
|Advanced Solid Tumours (ASTs)
|This Phase I clinical trial termed the FPX-01-01 program is a dose-escalation study that will investigate the safety and tolerability of [225Ac]-FPI-1434 as a single dose injection in patients with ASTs. [225Ac]-FPI-1434 is a targeted alpha radioimmunoconjugate that consists of a humanized monoclonal antibody targeting the insulin-like growth factor-1 receptor 1 (IGF-1R), the sponsor's proprietary Fast-ClearTM Linker, a bifunctional chelate, and actinium-225. Patients will be screened for target expression with the imaging agent [111In]-FPI-1547. As well as evaluating the safety and tolerability of this targeted alpha-emitting radiotherapeutic, a maximum of 30 patients will be treated and followed up for safety and for signs of efficacy.
|The imaging agent [111In]-FPI-1547 contains the same targeting antibody, Linker, and bifunctional chelate as the [225Ac]-FPI-1434 therapeutic form, however it will contain indium-111 in place of actinium-225. Only those patients who have IGF-1R expression will be receiving the [225Ac]-FPI-1434 therapeutic radioimmunoconjugate. The sponsor uses its proprietary Fast-ClearTM Technology Platform to convert molecules into radiopharmaceuticals. Fast-ClearTM linkers promote increased clearance of radoisotopes – the linkers are engineered to improve the safety of radiopharmaceuticals without impacting efficacy.
|Five Prime Therapeutics, Inc.
|Breast, Ovarian and Endometrial Cancers Over-expressing B7-H4
|The study objective of this Phase Ib dose expansion clinical trial is to assess the safety, tolerability, pharmacokinetics (PK) and potential preliminary clinical benefit of FPA150 monotherapy in patients with breast, ovarian and endometrial cancers that over-express B7-H4. A particular cohort of patients in the Phase Ib arm of the study will undergo pre- and on-treatment biopsies to assess the pharmacodynamic effects of FPA150 on the cancer and the cancer microenvironment, including changes in markers of tumour immune infiltrates and cytokine levels.
|The primary endpoints for the Phase Ib portion will include objective response rate (ORR), duration of response and progression-free survival (PFS). The drug candidate is a novel, fully human, non-fucosylated monoclonal antibody targeting B7-H4. B7-H4 expression typically identified in multiple solid cancers, including breast and gynaecologic cancers. FPA150 exhibits a dual mechanism of action: blocking the T cell checkpoint activity of B7-H4 as well as delivering ADCC against cancer cells expressing B7-H4.
|Non-Small Cell Lung Cancer (NSCLC)
|This Phase I/II study will investigate the recommended dose, safety, tolerability and clinical activity of ADXS-503 firstly administered solely and then in combination with a checkpoint inhibitor in approximately 50 patients with NSCLC in different lines of therapy in up to 20 clinical centres across the U.S.
|This clinical trial will be part of the ADXS-HOT regimen which is a cancer-type specific immunotherapy program which exploits the sponsor’s proprietary Lm technology platform to target hotspot mutations that commonly occur in specific cancer types as well as other proprietary, tumor-associated antigens. ADXS-HOT drug candidates are an off-the-shelf treatment, intended to potentially treat all patients with a specific cancer type, without the need for pretreatment biomarker testing, DNA sequencing or diagnostic testing.
|Non-Alcoholic Steatohepatitis (NASH) with Biopsy
|This Phase II clinical trial is of a prospective, multi-centre, randomized, placebo-controlled multiple-arm study design recruiting male hypogonadal biopsy-confirmed NASH subjects with grade F2/F3 fibrosis. The expected duration of treatment is a 36-week period.
|LPCN 1144, an oral prodrug, bioidentical to testosterone, is being developed for the treatment of NASH and is currently being studied in a proof-of-concept liver imaging study for the purpose of assessing liver fat changes in hypogonadal men at risk of developing non-alcoholic steatohepatitis NASH using a magnetic resonance imaging (MRI) proton density fat fraction (PDFF) technique.
|Debiopharm International SA
|Metastatic (MTs) or Advanced Solid Tumours (ASTs) Harbouring an FGFR Fusion
|This study will recruit patients with MTs or ASTs whose cells show specific FGFR gene alterations, namely FGFR1, FGFR2 or FGFR3 gene fusions. The study objective is to demonstrate that the drug candidate Debio 1347 can derive clinical benefit to MT or AST patients with cancers harbouring a FGFR fusion.
|Debio 1347 is a novel orally formulated small molecule candidate shown from Phase I studies to be a selective FGFR 1, 2, 3 ATP competitive inhibitor. Clinical data from the phase I study revealed that patients with solid tumours with activating alterations in FGFR may benefit from treatment with the drug candidate.
|Novus Therapeutics, Inc.
|Otitis Media (OM)
|This is an exploratory Phase IIa study seeking to evaluate safety, tolerability, and efficacy of daily intranasal administration of the candidate OP0201 over 10 consecutive days in 50 children, aged 6 to 24 months, with acute OM. It will be of a randomized, double-blind, placebo-controlled, parallel-group study design investigating the effects of a 20 mg per day dose of OP0201 as an adjunct therapy to oral antibiotics. The overall study duration will be up to 30 days during which patients will receive 10 days of treatment. Multiple safety and efficacy endpoints will also be explored. This single centre clinical trial will be conducted entirely in the U.S.
|OP0201 is under clinical development as a potential first-in-class treatment option for OM, typically caused by eustachian tube (ET) dysfunction. OP0201 is a drug-device combination product comprised of a proprietary formulation of a surfactant dipalmitoylphosphatidylcholine (DPPC) and a spreading agent cholesteryl palmitate (CP) suspended in a propellant. The product is administered intranasally via a pressurized metered-dose inhaler and is intended to be used to restore the normal physiologic activity of the ET. As a combination, DPPC and CP are intended to effectively absorb onto the air-liquid interface of the mucosa and reduce the interfacial surface tension of the ET, which reduces the passive pressure required for the ET to open.
|Biohaven Pharmaceutical Holding Company Ltd.
|Generalized Anxiety Disorder (GAD)
|This Phase III study will investigate the efficacy and safety of troriluzole in GAD patients. The sponsor expects to recruit roughly 372 patients into a randomized, double-blind, placebo-controlled study across approximately 50 clinical centres in the U.S. Investigators will evaluate acute symptomatic treatment with troriluzole in GAD patients. The primary endpoint in this study will be the change in a patient's score based on the Hamilton Anxiety Rating Scale, a scale specific for assessing the severity and type of symptoms in patients with GAD.
|The secondary endpoint of this clinical trial will be to assess the safety, tolerability and pharmacokinetics of troriluzole. Troriluzole is classed as a third-generation prodrug and new chemical entity that modulates glutamate, a human excitatory neurotransmitter. The mechanism of action of troriluzole is in reducing synaptic levels of glutamate. Troriluzole causes an increase in glutamate uptake at the synapse, thereby augmenting the expression and function of excitatory amino acid transporters located on glial cells that play a key role in glutamate clearance from the synapse.
Week 18 Feb 2019 -22 Feb 2019
|ADCT-402 (loncastuximab tesirine) plus AstraZeneca’s IMFINZI (durvalumab)
|Advanced Diffuse Large B-Cell Lymphoma (DLBCL), Mantle Cell Lymphoma (MCL) or Follicular Lymphoma (FL)
|This open-label, single-arm study will incorporate a dose-escalation component, followed by a dose-expansion part in its study design. The dose-expansion part will comprise of as many as three expansion cohorts – one for DLBCL, one for MCL and one for FL in order to acquire additional safety and preliminary anti-tumor activity information at the maximum tolerated dose. Roughly 75 patients will be recruited for this study. In a 183-patient first-in-human Phase I clinical trial as a single chemotherapy agent, ADCT-402 showed an acceptable safety profile and protential anti-tumour activity in patients with relapsed or refractory B-cell non-Hodgkin lymphomas, and hence lead to commencement of this Phase I study using a combination therapy of ADCT-402 with AstraZeneca’s PD-L1 blocker IMFINZI® (durvalumab).
|ADCT-402, a proprietary antibody drug conjugate (ADC) designed to target and kill CD19-expressing malignant B-cells, is also being evaluated in an ongoing pivotal Phase II study in patients with relapsed or refractory (R/R) DLBCL. IMFINZI® (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.
|Advanced Solid Tumours
|This multi-centre Phase I study will investigate the pharmacokinetics, safety and tolerability of XL092. As part of the study design, the trial will be divided into dose-escalation and expansion phases. The dose-escalation phase of the study will enroll patients with advanced solid tumors, with the primary objective of determining a dose for daily oral administration of XL092 suitable for further evaluation. Based on the premise of positive data arising from the initial phase of the study, the expansion phase will seek to further explore the selected dose of XL092 in individual tumor cohorts, where safety, tolerability, and initial clinical activity will be assessed.
|XL092 is a next-generation oral tyrosine kinase inhibitor that targets VEGF receptors, MET, and other kinases implicated in the tumour's growth and metastasis.
|ReGenTree, LLC and Ora, Inc.
|Dry Eye Syndrome (DES)
|So far the sponsor, ReGenTree, has completed two Phase III clinical trials in the U.S. for DES which are ARISE-1 (Phase IIb/III) and ARISE-2 (Phase III). The initiation of ARISE-3 by ReGenTree in a partnership agreement with Ora, Inc., a full-service ophthalmic CRO, will investigate their new drug RGN-259 for the treatment of DES. ARISE-3 is a randomized, double masked, placebo controlled Phase III study which is based entirely on the results of the sponsor's previous clinical trials, ARISE-1 and ARISE-2. A total of 700 patients is expected to be enrolled into the study
|Earlier in July last year, the sponsor announced published data that RGN-259 promoted recovery of mucins and goblet cells, improved corneal integrity, and reduced inflammation in a dry eye mouse model and was equal to or more effective than prescription treatments such as cyclosporine A (Restasis®), lifitegrast (Xiidra®), and diquafosol (Diquas®).
Week 11 Feb 2019 – 15 Feb 2019
|Coronary Artery Disease
|This is a single centre Phase I clinical trial, double-blinded, randomized, placebo-controlled in study design, will investigate the tolerability, and composite haemostatic profile of VE-1902. Another aspect of the study design is its single daily oral dosing in two stages. The first will be a single ascending dose stage with a food effect cohort while the other will be a multiple ascending dose stage with seven-day repeat dosing.
|This Phase I study will evaluate safety, pharmacokinetics, and pharmacodynamics of VE-1902 in 100 to 120 healthy volunteers. This decoagulant candidate is the first PRrecision Oral AntiCoagulant (PROAC) of a US-based pharma company to enter into clinical development. Secondary endpoints of the study will investigate VE-1902’s pharmacokinetic and pharmacodynamic profiles.
|Actinium Pharmaceuticals, Inc.
|Actimab-A and Venetoclax
|Acute Myeloid Leukemia (AML)
|This Phase I/II combination study will enroll patients with relapsed or refractory AML or Acute Myeloid Leukaemia that have been previously treated with Venetoclax as well as patients that have never received venetoclax.
|Venetoclax is a BCL-2 or B-Cell Lymphoma 2 inhibitor that is jointly developed and marketed by AbbVie (ABBV) and Genentech. The sponsor postulates that the targeted radiation from Actimab-A can more effectively deplete MCL-1 levels thereby removing the AML cells' resistance mechanism and rendering them more susceptible to Venetoclax.
|Cystathionine Beta-Synthase (CBS) Deficient Homocystinuria/Classical Homocystinuria
|This is a double-blinded, randomized, placebo-controlled, Phase I/II study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical effects of OT-58 in patients with Cystathionine Beta-Synthase (CBS) Deficient Homocystinuria. This clinical trial will enroll up to 20 patients. The primary endpoint of the Phase I portion of the study is safety.
|OT-58 is a modified recombinant enzyme therapy undergoing development for patients afflicated by the rare disease Classical Homocystinuria. OT-58 is designed to help patients reduce their homocysteine levels and restore a normal lifestyle. Secondary endpoints of this study include evaluation of pharmacokinetic and pharmacodynamic parameters.
|Acute Muscle Spasms of the Back
|This is a double-blind, randomized, placebo-controlled, parallel group study of the efficacy and safety of Tolperisone or placebo administered as multiple doses three times a day (TID) in approximately 400 male and female subjects experiencing back pain due to or associated with muscle spasm. The primary endpoint is subject-rated pain due to acute back spasm using a Numerical Rating Scale (NRS; 0-10 scale, from no pain to worst possible pain). This Phase II trial will be conducted across approximately 45 sites in the US.
|Tolperisone is proposed to exhibit effective analgesic activity in addition to muscle relaxation because of its centrally-acting dual voltage gated calcium and sodium channel blocker mechanism of action.
Week 28 Jan 2019 -1 Feb 2019
|anti-PD1 monoclonal antibodies in combination with AV-MEL-1
|Metastatic Melanoma (MM)
|The sponsor announced on 16th January this month that its IND application to the FDA was approved for a Phase IB clinical trial to commence investigating its ROOT OF CANCER technology in patients with MM. The study represents the first time sponsor's cancer immunotherapy technology will be investigated in combination with checkpoint inhibitors. This Phase IB open-label, single-arm study will establish the safety of administering anti-PD1 monoclonal antibodies in combination with AV-MEL-1 in patients with measurable metastatic melanoma. The study trial will also monitor efficacy of the treatment for the estimated 14 to 20 patients. AIVITA's personalized patient-specific platform cancer technology has been developed to target the patient's tumor-initiating cells, which seed tumor growth, metastases and tumor recurrence.
|This treatment was tested recently in two Phase II studies in patients with advanced melanoma and approved for Phase III testing. These clinical studies demonstrated the efficacy of the approach in a randomized trial, yielding a 72% 2-year survival rate and a 54% 5-year survival rate.
|NeoImmuneTech, Inc. and Genexine
|Hyleukin-7 (IL-7-hyFc) and Atezolizumab (Tecentriq®)
|High-Risk Skin Cancer (HRSC)
|Due to a recent IND clearance by the FDA, the sponsor has intiated a Phase Ib/IIa clinical study to evaluate the safety and preliminary anti-tumour activity of Hyleukin-7 in combination with Tecentriq in approximately 80 patients with anti-PD-(L)1 naïve or relapsed/refractory high-risk skin cancers. The planned multi-centre open-label study will be conducted in the US.
|The sponsor's rationale is that the PD-(L)1 blockade is ineffective in inducing complete responses in most HRSC patients in particular those subjects with low tumor infiltrating lymphocytes. According to the underlying mechanism of action of Hyleukin-7, it is postulated that combining Hyleukin-7 with Tecentriq, a checkpoint inhibitor, would increase the number and/or intensity of responses to PD-1/PD-L1 inhibition.
|Advanced or Metastatic Solid Tumours
|This is an open-label, multicentre, single-arm Phase I clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumour activity of ADCT-601 in patients with advanced or metastatic tumours. Firstly the Phase Ia dose-escalation part will seek to determine the maximum tolerated dose of ADCT-601 and then the identified dose will be evaluated in the Phase Ib dose-expansion part. Roughly 75 subjects will be enrolled in the study.
|ADCT-601 is an antibody drug conjugate composed of a humanized monoclonal antibody against human AXL, conjugated using GlycoConnect™ site specific conjugation technology to a pyrrolobenzodiazepine (PBD) dimer toxin. In preclinical studies, ADCT-601 demonstrated potent and specific in vitro and in vivo anti-tumour activity in multiple cancer-derived models with different levels of AXL expression, and was stable and well tolerated. Increased AXL expression has been associated with various cancers. AXL has been shown to be a key driver of drug-resistance to targeted therapies, immuno therapies and chemotherapy in various animal models.
|Mirati Therapeutics, Inc.
|Advanced Solid Tumours Harbouring KRAS G12C mutation
|This Phase I/II dose escalation study will evaluate MRTX849 as a single agent in patients with advanced solid tumors that harbor KRAS G12C mutations. The trial will assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of MRTX849 in patients with molecularly-identified KRAS G12C-positive advanced solid tumours. After the selection of a recommended Phase II dose, a dose expansion study is anticipated to follow.
|Solid cancers characterized by KRAS G12C mutations are typically associated with poor prognosis and resistance to therapy, and there are few therapy options for such patients. At the preclinical stage, MRTX849 demonstrated a very strong blocking of KRAS-dependent signal transduction and cancer cell viability (EC50 ~10 nM). MRTX849 has also shown >1,000-fold selectivity for inhibition of KRAS G12C-compared with other cellular proteins.
|Promentis Pharmaceuticals, Inc.
|Moderate to Severe Trichotillomania in Adults
|This double-blind randomized Phase II study will investigate the safety, tolerability and efficacy of three oral doses of SXC-2023 in adult subjects with moderate to severe trichotillomania. This is a multicentre trial being conducted in 12 centres amounting to roughly 100 patients in total, divided into three active-dose cohorts and a placebo cohort. Clinical endpoints will be measurements of trichotillomania symptom severity and also measures of overall patient mental health and well-being, as well as other cognitive parameters. This Phase II trichotillomania monotherapy study will be followed by a Phase II add-on therapy study for another indication, obsessive-compulsive disorder.
|The mechanism of action for SXC-2023 is that it engages System xc-, a central nervous system target, addressing glutamatergic imbalance and oxidative stress. In trichotillomania pathology, functional deficits in glutamate signaling within the cortical-striatal pathway and mesolimbic system have been proposed to cause this impulse control disorder. Trichotillomania is a highly prevalent but underrecognized and disabling condition characterized by recurrent hair pulling, leading to noticeable hair loss and substantial adverse impact on quality of life.
|Innovent Biologics, Inc.
|Tyvyt (fully human anti-PD-1 therapeutic monoclonal antibody, generic name: sintilimab injection) in combination with capecitabine and oxaliplatin
|Advanced, Recurrent or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (GC or GEJ)
|This Phase III study (ORIENT-16) will investigate Tyvyt (fully human anti-PD-1 therapeutic monoclonal antibody, generic name: sintilimab injection), in combination with capecitabine and oxaliplatin, as a first-line treatment for patients with advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma (GC or GEJ). As a randomized, double-blind, multi-centre study design, this Phase III trial will be conducted in China to determine the efficacy and safety of Tyvyt (sintilimab injection) or placebo in combination with chemotherapy as a first-line therapy in patients with unresectable, locally advanced, recurrent or metastatic GC or GEJ.
|Tyvyt (sintilimab injection) is a class of immunoglobulin G4 monoclonal antibody, which binds to the PD-1 molecule on the periphery of T-cells thus blocking the Programmed Cell Death-1 Ligand-1 (PD-L1) pathway and thereby reactivating T-cells to annihilate the tumour cells.
Week 14 Jan 2019 -18 Jan 2019
|Autoimmune and Inflammatory Diseases
|The FDA has approved an IND application from I-Mab Biopharma, a China-based clinical stage biopharmaceutical company for TJM2, a humanized immunoglobulin G1 (IgG1) targeting granulocyte-macrophage colony-stimulating factor (GM-CSF), currently the best-in-class potential to treat autoimmune and inflammatory diseases. This Phase I initial first-in-human (FIH) single dose study will investigate safety, tolerability, pharmacokinetics/pharmacodynamics and immunogenicity of TJM2 in healthy volunteers (including Chinese subjects) in the United States.
|GM-CSF is a critical pro-inflammatory cytokine that plays a pivotal role in tissue inflammation and destruction in autoimmune and inflammatory diseases such as rheumatoid arthritis and osteoarthritis.
|Moderate to Severe Alopecia Areata (AA)
|The sponsor's Phase IIa study met the primary efficacy endpoint in improving hair regrowth on the scalp relative to baseline at week 24 as measured by the Severity of Alopecia Tool (SALT) score (100 point scale). In addition to meeting the primary efficacy endpoint, subjects under investigation also met all secondary endpoints in the study. On the back of this positive Phase IIa data for PF-06651600, a pivotal Phase IIb/III trial will enroll an estimated 660 patients and will be a double-blind, placebo-controlled, dose-ranging study to evaluate the safety and effectiveness of PF-06651600 in adults and adolescents (12 years and older) who have 50% or greater scalp hair loss.
|AA is an autoimmune disease caused by the body's immune cells attacking healthy hair follicles, resulting in moderate to severe hair loss, often starting with smooth, round patches. The JAK pathways are believed to play an important role in such inflammatory processes and PF-06651600 is an oral JAK3 inhibitor that is also under investigation for the treatment of rheumatoid arthritis, Crohn?s disease and ulcerative colitis.
Week 26 Nov 2018 -30 Nov 2018
|CD38xCD3 Bispecific Antibody GBR 1342
|On 7 November 2018, the sponsor announced commencement with a Phase I study in solid tumors for its CD38xCD3 bispecific antibody GBR 1342. This was initiated on the basis of a recently completed ex vivo translational study in multiple solid tumours utilizing the clinically validated CANscript™ platform, where treatment with GBR 1342 revealed predictive responses in various tumour types. GBR 1342 is part of the sponsor's proprietary BEAT® (Bispecific Engagement by Antibodies based on the T cell receptor) platform and simultaneously targets CD38 and the CD3 T cell co-receptor. This trial will assess the safety and tolerability of increasing doses of GBR 1342, and will also evaluate biomarkers, immunogenicity, and additional measures of disease activity.
|GBR 1342 is part of the sponsor's proprietary BEAT® platform and simultaneously targets CD38 and the CD3 T cell co-receptor. CD38 is an antigen known to be involved in hematological malignancies as well as some solid tumours. BEAT® is the sponsor's proprietary technology for the production of bsAbs. With BEAT® technology, Glenmark's researchers have resolved past production obstacles encountered with bsAbs, and can efficiently manufacture these molecules at clinical and commercial scale.
|LUTONIX® 014 Drug-Coated Balloon (DCB) IDE
|Narrowed or Obstructed Arteries below the Knee
|This LUTONIX® Drug-Coated Balloon (DCB) IDE, Phase I clinical trial for a below-the-knee (BTK) indication, is of a prospective, global, multicentre, randomized, controlled study design comparing the LUTONIX® 014 DCB to standard angioplasty for the treatment of narrowed or obstructed arteries below the knee. This trial made use of both proportional/binary and Kaplan Meier analyses to assess safety and efficacy. The primary safety endpoint—freedom from composite all-cause death, above the ankle or major reintervention of the treated limb through 30 days was met demonstrating a statistically significant safety equivalence between the LUTONIX® 014 DCB and standard PTA catheter, in both the proportional/binary and Kaplan Meier analyses.
|The primary efficacy endpoint investigated used a composite measurement of limbs saved from amputation and the openness of arteries, known as primary patency. By proportional/binary analysis, at six months there was an improvement in primary efficacy of 10.2% (DCB: 73.7% and PTA: 63.5%, p=0.0273, not-significant). The more commonly used Kaplan Meier analysis of the primary efficacy endpoint revealed a significant difference of 14.6% (DCB: 85.3%, PTA: 70.7%, p<0.001). Further analyses are planned for 12-, 24- and 36-month follow-ups.
|TAVO™ (in combination with Merck’s KEYTRUDA®)
|Late-stage Triple Negative Breast Cancer (TNBC)
|The sponsor reported on 6 November preliminary data from KEYNOTE-695, a global, multicentre Phase IIb, open-label study of intratumoral delivery of TAVO™ (tavokinogene telseplasmid / IL-12) with intravenous KEYTRUDA® (pembrolizumab) in patients with unresectable, advanced melanoma. Of the first nine subjects to complete 12 weeks of treatment and reach initial tumour evaluation (by RECIST v1.1), two subjects had a partial response, while one subject had disease stability (22% BORR and 33% DCR) and tumour responses occurred in both TAVO™ treated and untreated lesions.
|From 1 September 2018, 21 patients had been enrolled in the study. Out of the 21 patients, nine patients had completed 12 weeks of treatment and reached the first tumor evaluation point at approximately 12 weeks, while the remaining 12 patients had not yet reached the first tumor evaluation. All nine patients were previously treated and definitively progressed on anti-PD-1 therapies with 56% (5/9) having had more than one prior line of therapy. All enrolled patients had exceedingly low frequencies of intratumoral CD8+ peCTL (PD-1+/CTLA-4+) at screening with a notable increase in TIL density following treatment. Of the two responding patients, both had multiple prior rounds of anti-PD-1 therapy, with no response, and one had also progressed after 4 cycles of OPDIVO® and YERVOY® (ipilimumab), an FDA-approved anti-CTLA4 / anti-PD-1 antibody combination. Therapy responses were associated with treatment-related upregulation of immune-based transcripts in the tumor microenvironment, as well as increased frequencies of intratumoral T cells within three weeks of therapy.
|Chikungunya Fever (CF)
|Themis Bioscience recently completed a Phase II study designed to assess the safety, tolerability and immunogenicity of MV-CHIK to protect against CF. The trial, which included 263 healthy participants, was conducted at four study sites in Austria and Germany. The primary endpoint, defined as the presence of neutralizing antibodies against Chikungunya, four weeks after administration of one or two MV-CHIK injections, was met across all treatment groups. The study demonstrated that MV-CHIK induced neutralizing antibodies against Chikungunya in all treatment groups after two injections, with seroconversion rates ranging from 86.4% to 100.0%, depending on dose and administration schedule. The data also demonstrated that pre-existing antibodies against the measles vaccine virus did not affect immunogenicity against Chikungunya. Adverse events related to the vaccine were highly similar between groups with no serious effects recorded.
|Currently CF, a mosquito-transmitted disease, has no treatment or prevention options and was recently added to the Tropical Disease Priority Review Voucher Program of the FDA. The double-blinded, randomized, placebo- and active comparator- controlled Phase II study also evaluated the impact of pre-vaccination against the vector in two groups that received Priorix®, the live attenuated measles, mumps and rubella (MMR) vaccine, prior to MV-CHIK administration
|Endo International Plc
|Collagenase Clostridium Histolyticum (CCH)
|Edematous Fibrosclerotic Panniculopathy (EFP or more commonly "Cellulite")
|This Phase IIb study enrolled 375 women with moderate or severe EFP (cellulite) aged 18 years or older in the United States. Each subject received up to three treatment sessions of CCH (0.84 mg / session) or placebo with each treatment session occurring approximately 21 days apart. Twelve injections were administered into cellulite dimples during each session across an entire treatment quadrant – left or right buttock or left or right posteriolateral thigh. At both the outset and conclusion of the study period (28 days after the last treatment), EFP severity was examined by each patient and clinician using two photonumeric EFP severity scales developed by the sponsor and other third-party experts. The scales – the Photonumeric Cellulite Severity Scale (PCSS) – are 5-point scales ranging from 0 (no EFP) to 4 (severe EFP) that measure improvement in the appearance of EFP. The study's primary endpoint was the proportion of composite responders at Day 71 defined as subjects with a 2-point improvement in severity from baseline in the clinician-reported (CR) PCSS and a 2-point improvement in the patient-reported (PR) PCSS. Subjects receiving CCH showed statistically significant levels of improvement in the appearance of EFP with treatment, as measured by the trial's primary endpoint (p<0.001), compared to those subjects receiving placebo.
|Additional endpoints included a composite of 1-point responders, the percentage of responders with 1-point and 2-point improvements on the CR-PCSS and PR-PCSS, assessment of improvement by patient and clinician using the Global Aesthetic Improvement Scale (GAIS); subject satisfaction, and change in the Hexsel cellulite severity scale. CCH was well-tolerated by all dose groups with most adverse events (AEs) being mild to moderate and primarily limited to the local injection area; 92 percent of all related AEs were mild to moderate in the CCH group compared to 96 percent in the placebo group; the most common AEs were expected and included injection site bruising (approximately 75 percent) and injection site pain (approximately 59 percent).
|Urovant Sciences, Inc.
|Overactive Bladder (OB)
|The sponsor recently announced it has completed enrollment for an international Phase III study, EMPOWUR, which will be evaluating the safety and efficacy of Vibegron as a treatment for adults with OB. EMPOWUR has enrolled a total of 1,530 patients meeting the inclusion criteria and these subjects will be randomized across 216 study sites into one of three groups for a 12-week treatment period with a four-week safety follow up period: Vibegron 75 mg administered orally once daily; placebo administered orally once daily; or tolterodine ER 4 mg administered orally once daily. The study will have co-primary endpoints which are: 1) Change from baseline in the average number of micturitions per 24 hours in all patients and 2) Change from baseline in the average number of urge urinary incontinence (UUI) episodes per 24 hours in patients who have one or more UUI episodes per day prior to treatment.
|Vibegron is an investigational oral therapy acting as a beta-3 adrenergic agonist. The EMPOWUR Phase III study is of a randomized, double-blind placebo- and active comparator controlled design to be investigated in men and women with symptoms of overactive bladder, including frequent urination, sudden urge to urinate, and urge incontinence or leakage. Also as an extension study, the first 507 patients who complete the EMPOWUR trial will be enrolled in a 40-week double-blind trial to evaluate the safety of longer-term treatment of Vibegron.
|Highly Refractory Advanced or Metastatic Renal Cell Carcinoma (RCC)
|On 5 November 2018, the sponsor announced it has met primary end point for its TIVO-3 trial, a Phase III randomized, controlled, multi-centre, open-label study to compare Tivozanib (FOTIVDA®) to sorafenib in 351 subjects with highly refractory advanced or metastatic RCC. The study met its primary endpoint by demonstrating a statistically significant benefit in progression-free survival (PFS). Tivozanib demonstrated a 44% improvement in median PFS and 26% reduction in risk of progression or death (Hazard Ratio [HR]=0.74, p=0.02). Median PFS was 5.6 months for Tivozanib compared to 3.9 months for sorafenib. Additionally the TIVO-3 study enrolled patients with RCC who have failed at least their two previous regimens. Among these, approximately 26% of patients received checkpoint inhibitor therapy in earlier lines of treatment. Tivozanib PFS was longer than sorafenib both in patients who received prior checkpoint inhibitor therapy and those who did not.
|Tivozanib is administered orally acting as a VEGF receptor tyrosine kinase inhibitor. As for the secondary endpoint analysis of overall survival (OS), this outcome was not mature at the time of the final PFS analysis, with only 46% of potential OS events having been reported. At the time of the preliminary OS analysis, no statistically significant difference in OS was observed (HR=1.06, p=0.69). The secondary endpoint of overall response rate for patients receiving tivozanib was 18% compared to 8% for patients receiving sorafenib (p=0.02). Tivozanib was generally well-tolerated, with grade 3 or higher adverse events consistent with those observed in previous Tivozanib trials. Infrequent but severe adverse events reported in greater number in the Tivozanib arm were thrombotic events similar to those observed in previous Tivozanib studies. The most common adverse event in patients receiving Tivozanib was high blood pressure, an adverse event known to reflect effective VEGF pathway inhibition.
|non-fatal Cardiovascular (CV) Death, non-fatal Myocardial infarction (MI) and non-fatal Cerebrovascular Accident (CVA) in Type II Diabetes
|The sponsor announced on 5 November 2018, that Trulicity® (Dulaglutide) significantly reduced major adverse cardiovascular events (MACE), a composite endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (heart attack) or non-fatal stroke in its REWIND study. The REWIND (Researching cardiovascular Events with a Weekly INcretin in Diabetes) study was a multicentre, randomized, double-blind, placebo-controlled trial designed to assess the effect of Trulicity 1.5 mg, a weekly glucagon-like peptide 1 receptor agonist (GLP-1 RA), compared to placebo, both added to standard of care, on cardiovascular (CV) events in adults with type 2 diabetes. The primary CV outcome was the first occurrence of MACE (the composite of CV death or non-fatal myocardial infarction or non-fatal stroke). The REWIND study revealed a median follow-up period of more than 5 years, the longest for a CV outcome trial in the GLP-1 receptor agonist class. In comparison, other CV outcome trials had more people with a higher baseline A1C (a marker of % glycated heamoglobin) of and a greater percentage of patients who had established CV disease.
|The REWIND secondary outcomes included each component of the primary composite CV outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all-cause mortality. This was an international study of 9,901 subjects from 24 countries who had a mean duration of diabetes of 10 years and a mean baseline A1C of 7.3 percent. Thirty-one percent of subjects had prior (or established) CV disease at baseline. Prior CV disease in REWIND was defined as prior myocardial infarction, prior ischemic stroke, prior unstable angina, prior revascularization (coronary, carotid, or peripheral), prior hospitalization for ischemia-related events (unstable angina or myocardial ischemia on imaging, or need for percutaneous coronary intervention), or prior documented myocardial ischemia.
|Hip Osteonecrosis (ON)
|Bone Therapeutics recently decided to stop its PREOB Phase III trial following the recommendations of the Data and Safety Monitoring Board (DSMB) citing that at final analysis the primary objective is likely not to be achieved. The Phase III study investigated 44 patients who have ON of the hip. In an interim examination of the trial data, the DSMB said treatment with PREOB, an autologous osteoblastic cell therapy derived from patient bone marrow, was well-tolerated, but not as effective as aniticpated by the sponsor.
|As a follow up to the termination of the Phase III study of PREOB, the sponsor has indicated that it will focus its cell therapy development activities and resources on its off-the-shelf, allogeneic platform, ALLOB. The sponsor also cited that allogenic cells are differentiated cells that are derived from ex vivo cultured bone marrow cells from healthy donors, claiming such cells have demonstrated stronger osteogenic properties than PREOB cells.
Week 29 Oct 2018 -2 Nov 2018
|Combination of Opdivo and Yervoy
|Metastatic Urothelial Carcinoma (MCB pretreated with platinum-based chemotherapy)
|This CheckMate -032 study, was a Phase I/II trial demonstrating that patients who were treated the combination of Opdivo 1 mg/kg plus Yervoy 3 mg/kg (O1:Y3) experienced a higher objective response rate (ORR) compared to those who received Opdivo 3 mg/kg plus Yervoy 1 mg/kg (O3:Y1) or Opdivo alone. Patients in the study were heavily pretreated, with most receiving at least two prior treatment regimens. There was minimum follow-up of 7.9 months for the expanded cohort of patients receiving O1:Y3, with the ORR determined to be 38% (95% Confidence Interval [CI]: 28-49). For patients receiving O3:Y1, at a minimum follow-up of 38.8 months the ORR was 27% (95% CI: 19-37), and for patients receiving Opdivo alone, at a minimum follow-up of 37.7 months the ORR was 26% (95% CI: 16-37).
|Median progression-free survival (PFS) and overall survival, secondary endpoints in the study, were numerically longer in the O1:Y3 treatment cohort (4.9 and 15.3 months, respectively [95% CI: 2.7-6.6 and 10.1-27.6]) compared to the O3:Y1 (2.6 and 7.4 months, respectively [95% CI: 1.4-3.9 and 5.6-11.0]) and Opdivo monotherapy (2.8 and 9.9 months, respectively [95% CI: 1.5-5.3 and 7.3-21.1]) cohorts. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 27%, 31% and 39% of patients treated with Opdivo monotherapy, O3:Y1 and O1:Y3, respectively; grade 5 TRAEs (pneumonitis) were observed in one patient each in the Opdivo monotherapy and O3:Y1 groups; no grade 5 TRAEs were observed in the O1:Y3 group. The combination of Opdivo plus Yervoy was also well tolerated, with 13% discontinuation rate due to TRAEs in the O1:Y3 group and 13% discontinuation rate in the O3:Y1 group. The discontinuation rate due to TRAEs in the Opdivo monotherapy group was 4%.
|Scarless Laboratories, Inc.
|Scarless Laboratories, Inc. (SLI) has received clearance from the FDA to enter a Phase I/IIa Clinical Study of its novel therapeutic peptide, SLI-F06, to promote wound healing and improve scar appearance. This double-blind multicentre trial, will be composed of two parts: Part A will be a Phase I safety/proof of concept study of wound healing and scar appearance in multiple small surgical wounds made in the section of abdominal skin scheduled to be excised during routine abdominoplasty (“pre-abdominoplasty” patients). At predefined times, “pre-abdominoplasty” patients in Part A will undergo abdominoplasty to start Part B. Part B will be a Phase IIa safety and efficacy study of postoperative scar appearance in patients undergoing abdominoplasty. Phase IIa is intended to provide the safety and efficacy data required to move into a larger Phase IIb study with an expanded patient population.
|Research on the SLI-F06 peptide has been conducted for over twenty years at the UCLA. The California NanoSystems Institute (CNSI) incubator at UCLA through preclinical testing in pig models demonstrated significant efficacy in improving scar appearance and strength and reducing scar size. According to FDA preclinical safety study requirements, SLI-F06 was found to be safe in the rat and pig at maximum feasible doses. SLI-F06 exhibits an unique mechanism of action by activating the wound cells to heal with less scarring by promoting cell migration, i.e. the cells move to the wound faster than they normally would, whilst through cell differentiation and function, the cells mature faster and work more effectively in the wound.
|Takeda Pharmaceutical Company
|Investigational Subcutaneous Formulation of Vedolizumab
|Moderately to severely active Ulcerative Colitis (UC)
|VISIBLE 1 is a pivotal phase III study, of randomized, double-dummy, double-blind, placebo-controlled design, with a vedolizumab intravenous (IV) reference arm, to evaluate the safety and efficacy of an investigational subcutaneous (SC) formulation of vedolizumab as maintenance therapy in adult patients with moderately to severely active UC who have achieved clinical response at week 6 following two doses of open-label vedolizumab IV therapy at weeks 0 and 2. This trial enrolled 383 subjects, all of whom had inadequate response with, loss of response to, or intolerance to corticosteroids, immunomodulators, or anti-TNF therapy prior to being enrolled. Patients who achieved clinical response at week 6 (n=216, 56.4%) were randomized into one of three treatment groups, vedolizumab SC 108 mg and placebo IV (n=106), vedolizumab IV 300 mg and placebo SC (n=54), or placebo SC and placebo IV (n=56). SC doses were given every two weeks and IV doses were given every eight weeks. At week 52, a statistically significant proportion of patients receiving vedolizumab SC achieved clinical remission (with clinical remission being defined as a complete Mayo score of ¢2 points and no individual subscore >1 point) compared to patients receiving placebo (46.2% vs. 14.3%; p<0.001). A similar rate of clinical remission was observed in the vedolizumab IV reference arm (42.6%).
|Vedolizumab SC was statistically superior to placebo in key secondary endpoints of mucosal healing, with mucosal healing being defined as a Mayo endoscopic subscore of ¢1 point, (56.6% vs. 21.4%; p<0.001) and durable clinical response? (64.2% vs. 28.6%; p<0.001). Vedolizumab SC was also numerically higher to placebo in achieving durable clinical remission, which is defined as clinical remission at weeks 6 and 52. (15.1% vs. 5.4%; p=0.076) and corticosteroid-free clinical remission* (28.9% vs. 8.3%; p=0.067), with these results not being of statistical significance. Similar findings were observed for these endpoints in the vedolizumab IV reference arm. Additionally, a subgroup analysis showed clinical remission rates were significantly greater with vedolizumab SC compared to placebo in anti-tumor necrosis factor-alpha (TNF )-na?ve (53.7% vs. 18.9%; p<0.001) and anti-TNF -failure patients (33.3% vs. 5.3%; p=0.023). *Footnote: Corticosteroid-free clinical remission is defined as patients using oral corticosteroids at baseline (week 0) who have discontinued oral corticosteroids and are in clinical remission at week 52. PBO: n=24, VDZ SC: n=45, VDZ IV: n=21.
Week 22 Oct 2018 -26 Oct 2018
|Treatment-resistant Guillain-Barr? Syndrome (GBS)
|FDA has cleared an Investigational New Drug (IND) application enabling Cellenkos™, biotechnology company to proceed with a Phase I clinical trial of CK0801, derived from 3rd party cord blood regulatory T cells, in subjects with bone marrow failure syndrome including aplastic anemia, myelodysplastic syndrome and myelofibrosis. Cellenkos™ submitted its IND application on May 11, 2018. The Phase I clinical trial of CK0801 will start in the third quarter of 2018 at The University of Texas MD Anderson Cancer Center, Houston, Texas.
|CK0801 represents a novel cellular treatment to bone marrow dysfunction arising from irregularities in the patient's immune system. It works to replace and replenish the defective regulatory T cells and inhibits the uncontrolled inflammatory signal generated by the cytotoxic T cells against a patients' own tissues. Such a strategy may lead to amelioration of the bone marrow inflammatory microenvironment as a result of the infused CK0801 which in turn may lead to the reversal of the hematopoietic arrest that will potentially derive clinical benefit.
|Psoriatic Arthritis (PsA)
|UCB, a biopharmaceutical company, announced yesterday the long-term data from its BE ACTIVE study, showing that response rates across musculoskeletal and skin manifestations with Bimekizumab continued to increase in the dose-blind study period after Week 12, through Week 24, and were sustained to Week 48 in psoriatic arthritis (PsA) patients. The study achieved its primary endpoint, with 46% of PsA patients who received Bimekizumab experiencing at least 50% improvement in PsA signs and symptoms (ACR50), versus 7% with placebo, at Week 12. These results were generally consistent regardless of prior exposure to an anti-TNF and were maintained to Week 48 across doses. At Week 48, ACR20/50/70 response rates were 70%/55%/43% for the 160 mg dose, 73%/57%/46% for the 160 mg dose with a loading dose, and 76%/63%/39% for the 320 mg dose. In addition, Psoriasis Area and Severity Index (PASI90) response rates at Week 48 were 70% for the 160mg dose with and without a loading dose, and 85% for the 320mg dose.
|BE ACTIVE, is a Phase IIb 48-week, randomized, double blind, placebo-controlled, dose-ranging study assessing the dose response, long-term efficacy and safety of Bimekizumab in adults with PsA, randomized 206 patients to five dose regimens to receive either placebo or Bimekizumab every four weeks by subcutaneous injection for 12 weeks. Patients then transitioned to a dose-blind period where all patients received Bimekizumab treatment for 36 weeks. Patient inclusion criteria were both TNF-naïve patients, as well as those who had been previously exposed to an anti-TNF biologic.
Week 15 Oct 2018 -19 Oct 2018
|Cardiovascular Disease (CVD) and Hyperlipoproteinemia (A)
|This randomized, double-blind, placebo-controlled, dose-ranging Phase II study included 286 patients with established CVD and high lipoprotein/Lp (a) (baseline mean of approximately 100 mg/dL [250 nmol/L] – more than three times the upper limit of normal). All subjects were treated for at least six months, with some treated up to one year. The primary study objective was to characterize the safety and tolerability of AKCEA-APO(a)-LRx and to inform dose and dose frequency selection for the planned Phase III cardiovascular outcomes study. A key finding was that it achieved statistically significant dose-dependent reductions of Lp(a) compared to placebo at all dose levels, including low monthly doses of AKCEA-APO(a)-LRx.
|The most common adverse event was injection site reactions (ISRs). ISRs were mostly mild and occurred in a minority of patients. There were no reports of any patient in the study experiencing a confirmed platelet level below 100,000/mm3. The incidence of platelet levels below normal (140,000/mm3) was comparable between the active (10.5%) and placebo (14.9%) groups. Roughly 90% of patients completed treatment and the rate of treatment discontinuation was comparable between the active and placebo groups.
|Type 2 Diabetes
|The TIMES 2 trial of the Phase III program for Imeglimin, an investigational therapeutic agent for type 2 diabetes, for patient registration in Japan has been completed. Otherwise referred to as TIMES (Trials of IMeglimin for Efficacy and Safety), the Imeglimin Phase III registration program in Japan includes three pivotal trials to evaluate the efficacy and safety of Imeglimin in over 1,100 patients. The TIMES 2 trial is a 52-week, open-label, parallel-group study to assess the long-term safety and efficacy of Imeglimin in Japanese patients with type 2 diabetes. In this particular study, Imeglimin is administrated as a monotherapy or combination therapy to over 700 patients with existing hypoglycemic agents, including a DPP4 inhibitor, SGLT2 inhibitor, biguanide, sulphonylurea and GLP1 receptor agonist.
|Imeglimin is the first clinical candidate in a new chemical class of oral agents called Glimins by the WHO. Imeglimin has a unique mechanism of action targetting mitochondrial bioenergetics. Imeglimin acts on all three key organs - the liver, muscles and pancreas, all of which play an important role in the treatment of type 2 diabetes and it has shown glucose lowering efficacy by increasing insulin secretion in response to glucose, improving insulin sensitivity and suppressing gluconeogenesis.
|Influenza Types A/H3N2 & B
|This Phase III trial called CAPSTONE-2 was a multicentre, randomized, double-blind study that evaluated the efficacy and safety of a single dose of baloxavir marboxil compared with placebo and oseltamivir in people 12 years or older who are at a high risk of complications from influenza. The CAPSTONE-2 study revealed that Baloxavir Marboxil has efficacy (reduced time to improvement of influenza symptoms) in influenza type A/H3N2 (median time of 75.4 hours and 100.4 hours; p<0.05) and type B (median time of 74.6 hours and 100.6 hours; p<0.05) versus placebo. Furthermore, results for the overall patient population of the study showed numerically shorter time to improvement of influenza symptoms of Baloxavir Marboxil versus oseltamivir with a median time to improvement of symptoms of 73.2 hours for Baloxavir Marboxil compared with 81.0 hours for oseltamivir (p=0.8347).
|Baloxavir Marboxil showed efficacy in comparison to placebo and oseltamivir for key secondary endpoints, including reducing the time that the virus continued to be released from the body (viral shedding; median time of 48.0 hours for Baloxavir Marboxil versus 96.0 hours for both placebo and oseltamivir; p<0.0001). Baloxavir Marboxil also lowered the use of antibiotics and incidence of influenza-related complications (3.4 percent and 2.8 percent respectively) compared to placebo (7.5 percent and 10.4 percent; p=0.01 and p<0.05). Baloxavir Marboxil had a numerically lower overall incidence of reported adverse events (25.1 percent) compared with placebo (29.7 percent) or oseltamivir (28.0 percent).
|Zealand Pharma A/S
|Short Bowel Syndrome (SBS)
|This Phase III global study which enrolled it first patient on the 4th October, 2018, seeks to demonstrate efficacy and safety of once- and twice-weekly subcutaneous injections of 10 mg Glepaglutide in SBS patients on parenteral support. 129 subjects will be enrolled at roughly 40 highly dedicated investigational sites across the United States, Canada and Europe. The study will be placebo-controlled, randomized, parallel-group, double-blind, and with fixed dose injection in design. The primary objective is to confirm the efficacy of glepaglutide in reducing parenteral support volume in SBS patients.
|The secondary objectives of the study will be to evaluate additional efficacy endpoints, as well as safety and tolerability. With recent FDA orphan drug designation being granted for Glepaglutide for SBS treatment, this is a long-acting GLP-2 analog therapy with an effective half-life of approximately 50 hours. The preceding Phase II Glepaglutide study in SBS patients showed increases in intestinal absorption following only 3 weeks of treatment, thereby providing the basis for initiating this global Phase III study.
Week 8 Oct 2018 -12 Oct 2018
|Veloce BioPharma, LLC
|Chemo-Associated Paronychia, or Inflammed Painful Nails
|This Phase IIb study is a multicentre, randomized, double-blind, vehicle-controlled designed clinical trial intended to evaluate the safety, tolerability and efficacy of two strengths of VBP-926 (1% PVP-I, 2% PVP-I) vs. vehicle in 102 subjects with chemotherapy-associated paronychia. The findings from this study showed that VBP-926 (2%) met the primary efficacy endpoint of grade-improvement on the Paronychia Severity Grading Scale. This is consistent with previous findings and VBP-926 was well-tolerated at both doses and provided both morphological resolution and symptomatic relief in affected nails.
|The key result in this study was that VBP-926 at the higher concentration met the primary efficacy endpoint. The 2% dose reached robust statistical significance for nail grade improvement from baseline to the end of therapy for change in the Paronychia Severity Grading Scale (p= 0.0003). Furthermore there were no reports of treatment-related serious adverse events. Moreover adverse events were mild in severity and reversible when treatment was discontinued.
|Eli Lilly and Company
|Ultra Rapid Lispro (URLi)
|Type 1 & Type 2 Diabetes
|Here there are two Phase III studies of LY900014 in Participants With Type 1 Diabetes (PRONTO-T1D) and of LY900014 Compared to Insulin Lispro in Participants With Type 2 Diabetes (PRONTO-T2D) which were randomized, double-blind, controlled, treat-to-target comparisons of ultra rapid lispro (URLi) and Humalog (insulin lispro), both in combination with either insulin glargine or insulin degludec in adults with type 1 and type 2 diabetes, respectively. The primary objective of each study, conducted in 1,222 and 673 participants, respectively, was to evaluate whether URLi is non-inferior to Humalog in reducing A1C from baseline after 26 weeks of treatment.
|For both populations, URLi demonstrated superior reduction in glucose excursions at both one and two hours during a meal test. However both study arms showed no significant difference in severe, nocturnal or overall hypoglycemia rates reported by study participants. Also for both studies, URLi showed overall safety and tolerability similar to Humalog.
|Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited
|ADCETRIS (brentuximab vedotin) in combination with CHP (cyclophosphamide, doxorubicin, prednisone)
|CD30-Expressing Peripheral T-cell Lymphoma (PTCL)
|In this Phase III study (ECHELON-2) as a double-blind, randomized, multicentre designed trial to compare the efficacy and safety of ADCETRIS (brentuximab vedotin) in combination with CHP (cyclophosphamide, doxorubicin, prednisone) with the standard-of-care CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in patients with frontline PTCL, results revealed that combination treatment with ADCETRIS plus CHP was superior to the control arm combination with CHOP for progression-free survival (PFS) as assessed by an Independent Review Facility (IRF; hazard ratio=0.71; p-value=0.0110).
|The ADCETRIS plus CHP arm also showed superior overall survival (OS), a key secondary endpoint, compared to CHOP (hazard ratio=0.66; p-value=0.0244). All other key secondary endpoints, including PFS in patients with systemic anaplastic large cell lymphoma (sALCL), complete remission rate and objective response rate were statistically significant in favour of the ADCETRIS plus CHP arm. There was comparability in the safety profile of ADCETRIS plus CHP in the ECHELON-2 trial to CHOP and was consistent with the established safety profile of ADCETRIS in combination with chemotherapy.
|Acorda Therapeutics, Inc.
|CVT-301 (INBRIJA, Investigational Inhaled Levodopa)
|OFF Periods in People with Parkinson?s Disease taking a Carbidopa/Levodopa Regimen
|The sponsor has presented a new post-hoc efficacy analysis from SPAN-PD, the pivotal Phase III trial of INBRIJA, at the International Congress of Parkinson’s Disease and Movement Disorders® taking place from Friday last week (October 5-9, 2018) in Hong Kong. INBRIJA is an investigational inhaled levodopa treatment for symptoms of OFF periods in people with Parkinson’s disease taking a carbidopa/levodopa regimen. At this time of publishing, the results have not yet been released in the public domain.
|Data from SPAN-PD, along with other clinical data, were included in the NDA for INBRIJA that was accepted for review by the FDA earlier htis year in February. The "OFF Periods" refers to when Parkinson’s disease progresses, people are likely to experience OFF periods, which are characterized by the return of Parkinson’s motor and non-motor symptoms, which can occur despite underlying baseline therapy.
|Five Prime Therapeutics, Inc.
|Bemarituzumab (FPA144), an Isoform-Selective FGF Receptor 2b (FGFR2b) Antibody, with Chemotherapy
|Advanced Gastric Cancer (GC) or Gastroesophageal Junction (GEJ) Cancer
|This double-blind randomized and controlled Phase III FIGHT (FGFR2b Inhibition in Gastric and Gastroesophageal Junction Cancer Treatment) trial will evaluate 15 mg/kg of bemarituzumab or placebo given every two weeks combined with modified FOLFOX6 (mFOLFOX6) chemotherapy in approximately 550 patients with GC or GEJ cancer whose tumors overexpress FGFR2b. This global Phase III registration clinical trial is the first prospective FGFR2b-specific front-line gastric study and will include approximately 250 sites in the U.S., Europe and Asia, including China, South Korea, Taiwan and Japan, where the incidence of gastric cancer is among the highest worldwide.
|For all FIGHT study sites, the primary endpoint is overall survival (OS), with key secondary endpoints being progression-free survival (PFS), objective response rate (ORR), safety and pharmacokinetic (PK) parameters.
|The intended planning is to conduct two identical placebo-controlled Phase III trials with approximately 240 patients per study. With the early potential therapeutic benefits of brimonidine tartrate (0.2%) observed in the previous Phase II study, Phase III efficacy and safety results will be examined after 28 days of treatment (primary endpoint assessment visit).
|Primary endpoints of the Phase III trials are the change from baseline to four weeks (Day 28) in Symptom Assessment iN Dry Eye (SANDE) score and the change from baseline to four weeks (Day 28) in lissamine green conjunctival staining scores.
Week 24 Sept 2018 -28 Sept 2018
|Checkpoint Therapeutics, Inc.
|CK-101 (or RX518)
|Non-Small Cell Lung Cancer (NSCLC)
|This was a Phase I dose-escalation portion of a Phase I/II clinical study. The study objective of the Phase I portion was to evaluate the safety and tolerability of ascending doses of CK‐101 in patients with advanced solid tumors to determine the maximum tolerated dose and/or recommend a suitable dose for the Phase II portion of the study. The Phase 2 portion will evaluate the safety and efficacy of CK-101 in patients with EGFR T790M mutation-positive NSCLC.
|On 11th September this year, the FDA granted Orphan Drug Designation to CK-101 (also known as RX518), the Sponsor’s third-generation epidermal growth-factor receptor (EGFR) inhibitor, for the treatment of EGFR mutation-positive Non-Small Cell Lung Cancer (NSCLC).
|Abeona Therapeutics, Inc.
|MPS IIIB (Sanfilippo Syndrome Type B)
|This Phase I/II study was approved by the Agencia Espanola de Medicamentos y Productos Sanitarios and is being conducted at Hospital Clinico Universitario of Santiago de Compostela, Spain. This will be the Sponsor’s second clinical trial conducted in Europe, alongside the ongoing Phase I/II study for patients with MPS IIIA (Sanfilippo syndrome type A).
|For this Phase I/II study, subjects will receive a single, intravenous infusion of ABO-101, which uses an AAV vector to introduce the functional NAGLU gene to treat subjects with MPS IIIB disease. Subjects will be evaluated at multiple time points post-injection for safety assessments and efficacy parameters. The study will also include potential efficacy assessments consisting of neurocognitive evaluations, biochemical assays and MRI data generated over one year of follow-up assessments
|Alcohol Use Disorder (AUD)
|This is a Phase II study of ANS-6637 for the treatment of AUD. The study design will be randomized, double-blind and placebo-controlled to assess outpatient alcohol consumption along with in-clinic laboratory measurements of alcohol craving.
|ANS-6637 is a selective ALDH2 Inhibitor that prevents pathophysiologic dopamine surge and associated craving without changes to basal dopamine. Such a pharmacological profile is anticipated to prevent craving and drug seeking behavior, thus it has the potential to be used as pharmacotherapy for any substance and behavior-based addiction.
|Moderate to Severe Plaque Psoriasis
|This is a multicentre, randomized, double-blind, parallel, placebo-controlled designed (1:1:1:1:1:1) Phase II study in subjects with moderate to severe psoriasis. The study randomized 267 patients to receive BMS-986165, a novel, oral, selective TYK2 inhibitor, in doses of 3 mg every other day (QOD) (n=44), 3 mg every day (QD) (n=44), 3 mg twice daily (BID) (n=45), 6 mg BID (n=45), 12 mg QD (n=44), or placebo (n=45). The primary endpoint was ≥75% reduction in the Psoriasis Area and Severity Index 75 (PASI 75) at Week 12. Key secondary endpoints included PASI 90 (≥90% reduction) and PASI 100 (≥100% reduction), as well as Dermatology Life Quality Index (DLQI), a quality of life measure.
|There were five findings, four of them of statistical significance - BMS-986165 achieved PASI 75 in 67%-75% of patients in the 3 mg twice daily and higher dose groups, compared to 7% for placebo at Week 12. PASI 75 response rates were 7% for placebo, 9% for 3 mg QOD (P=0.49 vs. placebo), 39% for 3 mg QD (P<0.001), 69% for 3 mg BID (P<0.001), 67% for 6 mg BID (P<0.001), and 75% 12 mg QD (P<0.001).
|Gilead Sciences & Galapagos NV
|Moderate to Severe Active Rheumatoid Arthritis
|This FINCH 2 Phase III clinical trial of global, randomized, placebo-controlled study design using Filgotinib, an investigational, selective JAK1 inhibitor, in adults with moderately-to-severely active rheumatoid arthritis and prior inadequate response/intolerance to biologic agents, achieved its primary endpoint in the proportion of patients achieving an American College of Rheumatology 20 percent response (ACR20) at Week 12.
|Additionally at weeks 12 and 24 of the study, the proportion of subjects achieving ACR50 and ACR70, low disease activity (LDA, DAS28(CRP) ó 3.2), and clinical remission (DAS28(CRP) < 2.6) were significantly higher for those subjects receiving once-daily Filgotinib 100 mg or 200 mg compared to subjects receiving placebo.
|Phase III (Failed)
|Severe Alcoholic Hepatitis
|This Phase III study failed to meet the primary endpoint of a significant improvement in overall survival through at least 91 days of treatment and assessment of VTL-308 using the Kaplan Meier statistical method. Noteworthy however was that there was a numerical improvement in survival in the ELAD-treated group between three months and one year following randomization.
|ELAD® is a cell-based therapy targeting the treatment of acute forms of liver failure. Unfortunately the secondary endpoint of proportion of survivors at study day 91 also showed no statistically significant difference between the groups.
|Merck KGaA & Pfizer
|Avelumab & Axitinib
|Advanced Renal Cell Carcinoma (RCC)
|This is a pivotal Phase III JAVELIN Renal 101 clinical trial evaluating BAVENCIO® (Avelumab) in combination with INLYTA® (Axitinib), compared with SUTENT® (Sunitinib) as initial therapy for patients with advanced RCC. The study revealed a statistically significant improvement in progression-free survival (PFS) by central review for subjects treated with the combination whose tumors had programmed death ligand-1‒positive (PD-L1+) expression greater than 1% (primary objective), as well as in the entire study population regardless of PD-L1 tumor expression (secondary objective).
|There were no new findings of safety signals and adverse events for BAVENCIO, INLYTA and SUTENT in this study which were consistent with the known safety profiles for all three medicines.
|Foamix Pharmaceuticals, Ltd.
|FMX101 (or FX2017-22)
|Moderate to Severe Acne
|This is a double-blind, randomized, vehicle-controlled Phase III study design which enrolled 1507 patients with moderate-to-severe acne at 89 sites in the US. Subjects were randomized to receive either FMX101 minocycline foam (4%) or vehicle foam once daily for 12 weeks. The co-primary efficacy endpoints were: (a) an absolute change from baseline in the number of inflammatory lesions, and (b) Investigator Global Assessment (IGA) treatment success, where success is defined as an IGA score of 0 or 1, and at least a 2-grade improvement (decrease) from baseline. Safety and tolerability were also investigated.
|Adverse events reported in this clinical trial was upper respiratory tract infection - viral (6.4% in both FMX101 and vehicle treatment groups). There were no treatment-related serious adverse events. A total of 5 subjects discontinued the study due to an adverse event (3 in the FMX101 treatment group and 2 in the vehicle treatment group). Overall FMX101 appeared to be generally safe and well-tolerated.
Week 17 Sept 2018 -21 Sept 2018
|PvP Biologics, Inc.
|Celiac Disease (CD)
|For this Phase I study investigating the safety, tolerability, and pharmacodynamics of Kuma062, a high enzymatic activity molecule under acidic conditions able to break down gluten in preclinical screening, PvP Biologics Inc. will be enrolling approximately 80 adults at two sites. One site at the academic Medical Center at the University of Michigan, enrolling normal volunteers. While the second site will be in Anaheim, enrolling normal volunteers as well as patients with biopsy-confirmed celiac disease with the inclusion criteria of maintaining a strict gluten-free diet.
|Kuma062's mode of action is that it degrades the immune-reactive parts of gluten before it leaves the stomach in order to decrease an immune response and reduce the symptoms and intestinal damage associated with CD.
|Moderate to Acute Pain Management
|This Phase I study will investigate the pharmacokinetics of NTM-001 continuous infusion compared with ketorolac IV every 6 hours of injection to the volunteer subject. The study is designed with 4 cohorts and will enroll 64 subjects at 2 sites.
|NTM-001 has been specifically designed to address the problem that after surgery, patients requiring continuous pain relief have few non-opioid options. Most current alternative options are ineffective due to the additional requirement of opioids or necessitate multiple doses over the course of 24 hours.
|Gilead Sciences and Galapagos NV
|Active Ankylosing Spondylitis (AS)
|With this Phase II TORTUGA study, Filgotinib, an investigational, selective JAK1 inhibitor, achieved its primary efficacy endpoint in adults with moderately to severely active ankylosing spondylitis (AS). In the study, patients treated with Filgotinib achieved significantly greater improvements in AS Disease Activity Score (ASDAS), the primary endpoint, at Week 12, with a mean change from baseline of -1.5 versus -0.6 for those treated with placebo (p<0.0001). More patients receiving Filgotinib also achieved an ASAS20 response compared to those treated with placebo (76 percent versus 40 percent, p<0.0001).
|It is noteworthy that the adverse events were generally mild or moderate in severity and were reported in an equal proportion of patients in the Filgotinib and placebo groups. Also for pharmacovigilance, laboratory changes were consistent with those previously reported for Filgotinib, and no new safety signals were observed in the study. There was only one treatment-emergent serious adverse event reported for a patient receiving Filgotinib who experienced pneumonia and recovered after hospital-based antibiotic treatment.
|Distal Renal Tubular Acidosis (dRTA)
|This was pivotal phase III study assessing ADV7103 in adults and children suffering from distal Renal Tubular Acidosis (dRTA). The aim of the study was to evaluate the efficacy, safety and acceptability of ADV7103, formulated in paediatric-friendly coated granules as an innovative oral product, that combines two active pharmaceutical ingredients. ADV7103 is given twice a day in contrast to the current standard of care (SoC), which are usually various unapproved products administered every four to six hours to attempt to re-balance the body's pH and to circumvent kalaemia.
|The study showed that normal blood bicarbonate levels were attained in most patients treated with doses of ADV7103 ranging from 0.75 to 8.45 mEq/kg/day. Mean doses of 1.7, 2.3, 3.8 and 6.1 mEq/kg/day ADV7103 were given, respectively, in adults, adolescents, children, and infants. Non-inferiority of ADV7103 vs. SoC or baseline literature data was consistently demonstrated (per protocol, intention-to-treat, as well as sensitivity analyses). Kalaemia was normalised with ADV7103 with only two doses per day.
|Horizon Pharma Plc
|Moderate-to-severe active Thyroid Eye Disease (TED)
|The Treatment of Graves? Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC) is a randomized, double-masked, placebo-controlled, parallel-group, multicenter study. OPTIC reached its target enrollment of 76 patients on Aug. 3, those remaining in screening were allowed to randomize for a final total of 83 patients. Patients will be randomized in a 1:1 ratio to receive eight infusions of teprotumumab or placebo every three weeks for 21 weeks. The primary endpoint is the responder rate of ò 2 mm reduction of proptosis, or bulging of the eye, in the study eye (without deterioration in the fellow eye) at week 24, in teprotumumab treated versus placebo treated patients. In addition, the secondary endpoints at week 24, include overall responder rate, percentage of participants with a Clinical Activity Score value of 0 or 1, mean change from baseline in proptosis measurement and the Graves? Ophthalmopathy Quality of Life questionnaire overall score. Safety is evaluated throughout the duration of the study. Teprotumumab is an investigational medicine and its safety and efficacy have not been established.
|Teprotumumab is a fully human monoclonal antibody (mAb) and a targeted inhibitor of the insulin-like growth factor 1 receptor (IGF-1R). Teprotumumab has received Breakthrough Therapy, Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration (FDA). The Phase III confirmatory study was launched last year in October, progressing from the randomized double-blind, placebo controlled Phase II study.
|Phase III (Flunked)
|Moderate to Severe Lupus Erythematosus (SLE)
|The TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) study failed to meet its endpoint of a statistically significant reduction in disease activity in patients with Systemic Lupus Erythematosus (SLE), measured by an index of symptoms at 12 months. The primary endpoint was measured by the SLE Responder Index 4 (SRI4) at 12 months. The TULIP program has two Phase III clinical trials, TULIP 1 and 2, that study the efficacy and safety of the drug compared to placebo in patients with moderately-to-severely active autoantibody-positive SLE who are receiving standard of care treatment. TULIP 1 randomized 460 patients in a 1:2:2 ratio to receive a fixed dose of the drug as an infusion of 150 mg anifrolumab, 300mg anifrolumab, or placebo every 4 weeks. TULIP 2 randomized 373 patients 1:1 for a fixed-dose IV infusion of 300mg of the drug or placebo every 4 weeks.
|Anifrolumab is a fully human monoclonal antibody that binds to subunit 1 of the type 1 interferon receptor. This blocks the activity of all type I interferons. About 60 to 80 percent of adult lupus patients have an increased type I interferon gene signature, which is correlated with disease activity.
Week 10 Sept 2018 -14 Sept 2018
|This was a Phase Ia (part A) study designed to evaluate the safety and tolerability of ascending doses of BC 007. In order to better discriminate possible safety signals, the study design was a blinded and placebo controlled. The assessment of safety and tolerability in an elderly cohort was a bridge to dosing elderly GPCR AAB positive subjects in Phase Ib (part B). Subjects in part A were confirmed to be GPCR AAB negative.
|The objective of the second part of the study (part B) was to determine the efficacy of BC 007 in neutralizing AAB against GPCR shortly after dosing compared to baseline and to find the optimal dose for the neutralization of the AAB in all subjects. This dose finding part of the study will be used in the Phase II/III trial with beta1-adrenergic receptor-AAB positive patients suffering from chronic heart failure.
|Diabetic Neuropathy Pain (DNP)
|Sponsor announced it has reached its funding goal reached to begin a global Phase IIb trial.
|NRD.E1 is a small, once daily, orally available molecule and has an unique mode of action exhibiting allosteric modulating properties of Lyn Kinase. The recently concluded 3-week, placebo-controlled, randomized Phase IIa proof of concept clinical study in 88 patients suffering from DNP showed clinically relevant reduction in patient-reported pain associated with DNP. NRD.E1 was well tolerated at all doses studied in the Phase IIa study.
|Promore Pharma AB
|Venous Leg Ulcers (VLU)
|Sponsor announced it has received approval from both the Swedish Medical Products Agency and the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products in Poland.
|Promore Pharma?s LL-37 in the HEAL (A Study in Patients with Hard-to-Heal Venous Leg Ulcers to Measure Efficacy and Safety of Locally Administered LL-37) Phase IIb study is anticipated to recruit 120 patients with VLUs with a size up to 40 square centimeters. Patients are divided into three arms, two where patients receive LL-37 and a placebo arm. The treatment will be ongoing for 13 weeks, two to three times a week in connection with regular change of wound dressing. The study design is a randomized and double blind one. The primary end point is the proportion of patients that have complete healed wounds.
|Transthyretin Cardiomyopathy (TC)
|Pfizer has announced its Phase III findings that Tafamidis therapy reduces death risk by 30 percent in patients with this distinct TC disease.
|This was a Global Phase III, open label long term extension safety study designed to obtain additional safety data for Tafamidis Meglumine 20 mg and 80 mg (or Tafamidis 61 mg where available), and to continue to provide enrolled subjects with Tafamidis for up to 60 months, or until subject has access to Tafamidis for Transthyretin (TTR) Amyloid Cardiomyopathy via prescription.
|Type 2 Diabetes
|Patient enrollment was completed in the TIMES 3 trial of a Phase III registration program.
|The TIMES 3 trial was a double-blind, placebo-controlled, randomized study design with an open-label extension period to evaluate the efficacy and safety of Imeglimin in combination with insulin. Imeglimin is an orally-available drug formulation with a novel mode of action that has demonstrated glucose lowering benefits by simultaneously targeting all three key organs - the liver, muscles and the pancreas in the treatment of type 2 diabetes.
Week 13 Aug 2018 -17 Aug 2018
|Smoldering Multiple Myeloma (SMM)
|This phase Ib study will evaluate the safety and tolerability of PVX-410, an investigational multi-peptide cancer vaccine, in approximately 20 SMM patients across multiple trial sites. It is an open-label investigator-sponsored study, investigating two different combinations of the study drugs; a combination of PVX-410 along with an investigational histone deacetylase (HDAC 6) inhibitor, citarinostat (CC-96241, Celgene) and a triple combination of the PVX-410 vaccine, citarinostat, and lenalidomide.
|SMM is an early precursor to a rare blood cancer known as multiple myeloma (MM), affecting the blood plasma cells. The rationale of administering PVX-410 in combination with the HDAC 6 inhibitor, citarinostat, with or without the immunomodulatory drug, lenalidomide, is that such combinations will supplement a targeted immune-mediated attack against MM cells.
|Bevacizumab biosimilar to CT-P16
|Metastatic colorectal cancer, metastatic breast cancer, non-small cell lung cancer, and glioblastoma
|Information in the public domain for this clinical trial is that following its Clinical Trial Application submission for a Phase III study to the National Authority of Medicines and Health Products, I.P. (Infarmed) of Portugal, Celltrion will conduct Phase III bridging studies for CT-P16 in approximately 150 sites in as many as 20 countries across Europe, Asia and South America.
|Roche, the originator of CT-P16, last financial year recorded global sales of about USD 6.7 billion for its brand Avastin?. Currently Bevacizumab is as an anti-vascular endothelial growth factor (anti-VEGF) drug prescribed for metastatic colorectal cancer, metastatic breast cancer, non?small cell lung cancer, and glioblastoma. However owing to the high cost of other anti-VEGF agents approved to treat eye disorders, Bevacizumab has rececntly been used off-label to treat diabetic retinopathy and age-related macular degeneration.
Week 6 Aug 2018 -10 Aug 2018
|Clover Biopharmaceuticals, Inc.
|Rheumatoid Arthritis (RA) and other Autoimmune Diseases
|A phase I trial undertaken in China designed to assess the pharmacokinetics, safety and immunogenicity of subcutaneously administered SCB-808 in the prefilled syringe formulation and originator drug Enbrel? in healthy volunteers.
|SCB-808 is being developed in the prefilled syringe formulation, which can potentially be self-administered by patients by injection in the convenience of their own homes. Such ready-for-injection formulations represents the overwhelming majority of Enbrel? prescriptions in Western countries. Therefore SCB-808 has the potential to address the unmet needs of Chinese patients for this class of drugs.
|Arcus Biosciences, Inc.
|TIGIT expressed Tumours
|A Phase I, multi-centre, open-label trial was undertaken to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AB154 as a monotherapy and in combination with AB122, Arcus Biosciences' anti-PD-1 antibody. Initially the dose-escalation part of this study will evaluate increasing doses of AB154 as a monotherapy and subsequently in combination with AB122.
|AB154 is a potent monoclonal antibody that selectively blocks a novel immune checkpoint called TIGIT. This is an important first-generation immune checkpoint target, as TIGIT is expressed on exhausted effector T cells, which may reside within tumours but are unable to mount an effective attack against the cancer cells.
|Transforaminal Lumbar Interbody Fusion (TLIF) Surgery
|This is a prospective, single-blinded, multi-centre, randomized, controlled phase I study. The primary study objective was to evalute effectiveness and safety of P-15L to local autologous bone (and allograft as extender where necessary) when applied in instrumented TLIF in subjects with Degenerative disc disease (DDD). The primary endpoint after 24 months of evalution will be evidence of continuous trabecular bridging bone in the intervertebral space; at least a 15-point improvement in Oswestry Disability Index (ODI), no report of new, worsening or persistent neurological deficit and no subsequent surgical intervention at the index level.
|The bioactive P-15 peptide in earlier studies was shown to enhance cell migration and induce osteoblast cell proliferation and differentiation. The P-15L formulation represents a new P15-based bone graft that is appropriate for lumbar spinal fusion. The new formulation comprises two new materials: 1) a porcine-derived anorganic bone mineral (ABM) as the anorganic bone matrix and 2) bovine collagen as the inert carrier for the anorganic bone granules as compared to the original i-FACTOR putty.
|Unresectable Metastatic Solid Tumours
|This is a phase I/IIa multicentre, open-label study. The study design will be composed of two parts: (i) an accelerated dose-escalation part to evaluate the safety and tolerability of intratumorally injected AGI-134 as a monotherapy, as well as to assess maximum tolerability of dose and recommended dosage for part 2 of the study; and (ii) as the dose expansion part of the recommended dosage, will be comprised of three cohorts and designed to determine the safety, tolerability and anti-tumor activity of AGI-134 as a monotherapy. The AGI-134 as a monotherapy will be evaluated in a basket cohort of multiple solid tumor types - metastatic colorectal cancer and head and neck squamous cell carcinoma, as well as in two additional cohorts will be evaluated in combination with an immune checkpoint inhibitor.
|In a pre-clinical murine melanoma model, treatment with AGI-134 demonstrated regression of established primary tumors and suppression of metastases development. The combination therapy with an anti-PD-1 immune checkpoint inhibitor, has the potential to improve the rate and duration of responses in multiple cancer types.
|Avelas BioSciences, Inc.
|Primary, Non-Recurrent Breast Cancer undergoing Surgery
|This is a multi-centre, open-label, single-arm phase II study designed to evaluate AVB-620 in primary, non-recurrent breast cancer patients undergoing surgery during two separate trial periods. The period 1 part of the study was completed in December 2017, which evaluated the optimal conditions to achieve differentiation between malignant and nonmalignant tissue using fluorescent signals in 31 patients. Commencing now with period 2 of the phase II study, an evaluation in approximately 108 additional patients will be made of the ability of AVB-620 to identify malignant tissue at or close to the surface of excised tissue and of tissue that would otherwise have been left behind.
|AVB-620 is administered intravenously in breast cancer patients undergoing either a lumpectomy with simultaneous sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND), or a mastectomy and simultaneous ALND. AVB-620 is a synthetic protease-activated peptide dye conjugate for the fluorescence detection and localization of potentially malignant tissue. By fluorescence imaging on a monitor, AVB-620 will assist the surgeon to assess potentially cancerous tissue within the primary tumour site, tumour margins, or in lymph nodes which drain the primary tumour site.
|Kala Pharmaceuticals, Inc.
|Dry Eye Disease
|The STRIDE 3 study is a multicentre, randomized, double-blind, placebo controlled, parallel-arm phase III study comparing KPI-121 0.25% to placebo, each subject being dosed four times a day (QID) for 14 days, in a cohort of approximately 900 patients with dry eye disease. Subjects who meet initial screening and eligibility (inclusion/exclusion) criteria will undergo a 2-week run-in period with placebo. Thereafter those subjects who continue to meet inclusion/exclusion criteria post run-in are randomized to either KPI-121 0.25% or placebo. The primary endpoint of the study will be ocular discomfort severity on day 15 of the trial period. This assessment will be based upon the subject's diary in which ocular discomfort is recorded daily over the entire course of the trial using a visual analog grading scale.
|In January 2018, Kala Pharmaceuticals, Inc. released topline results for the previous two phase III trials (STRIDE 1 and STRIDE 2), evaluating the safety and efficacy of KPI-121 0.25% versus placebo in patients with dry eye disease. KPI-121 0.25% achieved statistical significance for the primary sign endpoint of conjunctival hyperemia at Day 15 in the intent to treat (ITT) population in both Phase III trials.
|GE Healthcare and Lantheus Holdings, Inc.
|Coronary Artery Disease (CAD)
|This is an international, prospective, multicentre phase III study (as part of the AURORA programme) to evaluate diagnostic efficacy of Flurpiridaz 18F Injection positron-emission tomography (PET) myocardial perfusion imaging (MPI) in the detection of patients suspected of CAD, for whom an intracoronary angiography (ICA) has been indicated. Each patient will undergo a single-photon emission computed tomography (SPECT) MPI and Flurpiridaz 18F injection PET MPI prior to the performance of coronary angiography. The primary outcome of this study is the diagnostic efficacy (sensitivity and specificity) of Flurpiridaz 18F injection PET MPI for the detection of significant CAD. Enrollment is for a total of 650 patients.
|All subjects will receive two IV boluses of Flurpiridaz 18F injection in a large peripheral vein: 1 at rest and 1 during stress. The dosages of the IV Flurpiridaz 18F injections administered at rest and during stress conditions will not exceed a total of 14 mCi (520 MBq) for an individual patient. The secondary outcome of the study over a 60 day timeframe will be diagnostic efficacy of Flurpiridaz 18F injection PET MPI compared with SPECT MPI in the detection of CAD.