Date: 2016-11-14
Type of information: Results
phase: 2 - open-label extension
Announcement: results
Company: Corbus Pharmaceuticals (USA - MA)
Product: Resunab™- JBT-101 - (6aR,10aR)-3-(1,1-dimethylheptyl)-6a,7,10,10a-tetrahydro-1-hydroxy-6,6-dimethyl-6H-Dibenzo(b,d)pyran-9-carboxylic acid
Action
mechanism: cannabinoid receptor agonist. Resunab™ is a novel synthetic oral drug that is a preferential agonist to the CB2 receptor expressed on activated immune cells. CB2 activation triggers endogenous pathways that resolve inflammation and halt fibrosis. Pre-clinical and Phase 1 studies have shown Resunab to have a favorable safety, tolerability and pharmacokinetic profile. It has also demonstrated promising potency in pre-clinical models of inflammation and fibrosis. Resunab™ triggers resolution of inflammation by increasing production of "Specialized Pro-resolving Lipid Mediators of Inflammation" and anti-inflammatory mediators, while reducing production of pro-inflammatory mediators and reducing the numbers of immune cells in affected tissues. Resunab™ has direct effects on fibroblasts to halt tissue scarring. In effect, Resunab™ triggers endogenous pathways to turn "off" chronic inflammation and fibrotic processes, without causing immunosuppression. The FDA granted Orphan Drug Designation to Resunab™ for the treatment of systemic sclerosis in June of 2015 and recently designated Fast Track status to the Company's investigational drug development program in this indication.
Disease: diffuse cutaneous systemic sclerosis
Therapeutic area: Rare diseases - Autoimmune diseases
Country: USA
Trial
details: The Phase 2 study is a double-blind, randomized, placebo-control trial that will enroll up to 36 individuals with systemic sclerosis who will be treated for 84 days with a follow up period of 28 days. The study is expected to take approximately 16 months to complete and is designed to evaluate Resunab's safety and tolerability, along with its potential impact on clinical outcomes as measured by the Combined Response Index for Systemic Sclerosis, or CRISS score. In addition, multiple secondary endpoints will evaluate Resunab's effect on patient-reported outcomes, as well as its mechanism of action and effect on biomarkers in this patient population. (NCT02465437)
Latest
news: * On November 14, 2016, Corbus Pharmaceuticals announced positive topline results from its Phase 2 study evaluating Resunab ("JBT-101") for the treatment of diffuse cutaneous systemic sclerosis. JBT-101 out-performed placebo in the American College of Rheumatology (ACR) Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score, reaching 33% at week 16, versus 0% for placebo. The higher the CRISS score the greater the improvement; a CRISS score ? 20% (CRISS20) can be considered a medically meaningful improvement. The difference in CRISS scores between JBT-101 and placebo groups over the trial period was significant (p = 0.044). Differences in categorical levels of CRISS responses and changes from baseline in the five individual domains of the CRISS score also supported clinical benefit of JBT-101. The multi-center, double-blind, randomized, placebo-controlled Phase 2 study evaluated JBT-101's clinical benefit and safety in 27 subjects who received JBT-101 and 15 who received placebo. Subjects had disease duration up to 6 years and were allowed to receive stable doses of immunosuppressive drugs during this study. Subjects were randomized (2 to 1 overall JBT-101 to placebo ratio) to receive JBT-101 for the first four weeks at 5 mg once a day (n = 9), 20 mg once a day (n = 9), or 20 mg twice a day (n = 9) or placebo for the first four weeks, then all JBT-101 subjects received 20 mg twice a day for the next 8 weeks. All subjects were followed off study drug from weeks 13 through 16. Results: Group Median CRISS Score1, % (25 th percentile, 75th percentile) Week 4 Week 8 Week 12 Week 16 JBT-101 3% 19% 27.5% 33% n = 26 (0.6%, 11.4%) (0.3%, 69.2%) (1.9%, 67.8%) (0.8%, 82.1%) Placebo 1% 1% 1% 0% n = 15 (0.3%, 8.8%) (0.1%, 15.2%) (0.1%, 60.1%) (0.1%, 16%) There were no serious, severe, or unexpected adverse events related to JBT-101. One of 27 subjects (3.7% of subjects) who received JBT-101 withdrew from the study for an adverse event which was moderate dizziness. The primary treatment period has been completed and subjects are now enrolled in a one- year open label extension to obtain data on long-term safety and durability of response. Corbus received approval for an open-label extension to its Phase 2 clinical study of JBT-101 for systemic sclerosis from the FDA in April of 2016. The open-label extension enables all the participants in the study to receive JBT-101 for an additional 12 months. * On October 13, 2016, Corbus Pharmaceuticals announced that it has completed the Phase 2 study evaluating Resunab for the treatment of diffuse cutaneous systemic sclerosis. Corbus expects to report topline data from this study in the fourth quarter of 2016. * On June 16, 2016, Corbus Pharmaceuticals announced that it has completed patient enrollment in its Phase 2 clinical trial of Resunab for the treatment of diffuse cutaneous systemic sclerosis. The Company expects to report top-line results from this study in the fourth quarter of 2016. * On April 12, 2016, Corbus Pharmaceuticals announced that the FDA has granted approval for a 12-month open-label extension study of the ongoing Phase 2 clinical trial of Resunab for the treatment of diffuse cutaneous systemic sclerosis. The goal of the open label extension study is to provide all subjects with the option of receiving Resunab® following the completion of the 84-day treatment period in the ongoing double-blind placebo-controlled study and to collect long term safety and efficacy data on Resunab®. All subjects in the 12-month extension study will receive Resunab®, including those who received placebo in the current 84-day, double-blind placebo controlled trial. The same clinical endpoints used in the double-blinded placebo-controlled portion of the trial will be monitored throughout the 12-month extension study. Corbus launched its Phase 2 clinical trial of Resunab™ for the treatment of systemic sclerosis in August of 2015 (see below). The Company expects to report top-line results from this study in the fourth quarter of 2016. * On August 31, 2015, Corbus Pharmaceuticals announced that patient enrollment has commenced in the Phase 2 clinical study of Resunab™ for the treatment of diffuse cutaneous systemic sclerosis. Resunab is a novel synthetic oral endocannabinoid-mimetic drug that preferentially binds to a receptor called CB2 on immune cells and fibroblasts. Numerous pre-clinical and human ex-vivo models have demonstrated that the binding of Resunab to CB2 triggers the production of "Specialized Pro-resolving Lipid Mediators" (SPMs) that activate an endogenous cascade responsible for the resolution of inflammation and fibrosis. This resolution cascade restores chronically activated immune systems back to homeostasis and halts fibrosis, without causing immunosuppression. The study is being led by principal investigator Robert Spiera, M.D., Director of the Vasculitis and Scleroderma Program at the Hospital for Special Surgery, Weill Cornell Medical College in New York City. The study will be conducted in the United States at multiple clinics that specialize in the treatment of systemic sclerosis.
The median (25th percentile, 75th percentile) CRISS scores for the combined JBT-101 group and the placebo group at Weeks 4, 8, 12, and 16 are provided in the table below. The difference in CRISS scores between JBT-101 and placebo groups over the trial period was significant (p = 0.044), 1-sided mixed model repeated measures using rank transformed data.
Results of secondary efficacy outcome measures supported the finding of clinical benefit of JBT-101, including numerical superiority of JBT-101 in each of the five domains of the CRISS score, with divergence starting early at Week 4 or Week 8.
