IM025-017: Ph 2 study of BMS-986263 in Adults with Cirrhosis from NASH

• Research type

  Research Study

• Full title

  A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multiple-Dose Phase 2 Study to Evaluate the Efficacy and Safety of BMS-986263 in Adults with Compensated Cirrhosis from Nonalcoholic Steatohepatitis (NASH)

• IRAS ID

  1003240

• Contact name

  Lynsey Corless

• Contact email

  lynsey.corless@hey.nhs.uk

• Sponsor organisation

  Bristol-Myers Squibb International Corporation

• Eudract number

  2019-003932-22

• Research summary

  Short Title: Efficacy and Safety of BMS-986263 in Adults with Compensated Cirrhosis from\nNASH\nStudy Phase: 2\nRationale: Study IM025017 aims to demonstrate the antifibrotic efficacy of BMS-986263, using\na liver fibrosis histological endpoint, and the safety of BMS-986263, as assessed by adverse events (AEs), serious adverse\nevents (SAEs), laboratory results (including assessment of potential drug-induced liver injury [DILI]), vital signs, physical\nexaminations, electrocardiograms (ECGs), retinoid toxicity monitoring, infusion-related reaction monitoring, and bone mineral\ndensity (BMD) monitoring, in participants with nonalcoholic steatohepatitis (NASH) and compensated cirrhosis.\nNonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver\ndisease in the world today. NASH, which is the more advanced form of NAFLD, is defined as the\npresence of hepatic steatosis and inflammation with hepatocyte injury (ballooning), with or\nwithout fibrosis.1 NASH is associated with increased mortality rates due to cardiovascular-, liver-, and cancer-related deaths.\nCurrently, there are no approved drugs for the treatment of NASH. With the increasing prevalence of obesity and obesity-related\ndiseases, NASH could soon become the leading indication for liver transplantation and the leading cause of hepatocellular\ncarcinoma (HCC) globally.2 NASH patients with cirrhosis have a particularly high unmet medical need for effective therapies.\nAmong NASH patients, the stage of fibrosis is the strongest predictor of disease-specific mortality, and patients with cirrhosis are\nat the greatest risk for disease-related morbidity and mortality.3, 4, 5, 6 Patients with cirrhosis are particularly at increased risk for\npoor clinical outcomes, including hepatic decompensation events and the need for liver transplant. It is reasonable to assume\nthat an improvement in fibrosis would be predictive of clinical benefit, and a reduction of fibrosis in patients with compensated\ncirrhosis, if substantial, could lead to improvements in liver function and long-term clinical outcomes.\nOverall Design:\nThe primary study endpoint is the proportion of participants who achieve ≥ 1 stage improvement in liver fibrosis (NASH CRN\nFibrosis Score) on biopsy after 12 weeks of treatment.\nThe study includes:\n• A screening period of up to 8 weeks\n• A 12-week, double-blind treatment period, during which participants will receive 1 of the\nfollowing 3 treatments by intravenous (IV) infusion: 45 mg BMS-986263 once every week\n(QW), 90 mg BMS-986263 QW, or placebo QW\n• A follow-up period of 24 weeks\nParticipants meeting eligibility criteria during the screening period will enter the treatment period and be randomized to receive 45\nmg BMS-986263 QW, 90 mg BMS-986263 QW, or placebo QW by IV infusion in a double-blind manner. Participants will be\nstratified at Randomization by country (Non-Japan versus Japan). The Non-Japan participants will further be stratified by the\npresence of steatohepatitis on biopsy (yes versus no) and platelet count (< 130,000/μL versus ≥ 130,000/μL). At least 80% of\nparticipants will be required to have active steatohepatitis on the biopsy used to confirm eligibility. Participants will receive study\ntreatment via IV administration for a total of 12 weeks. Liver biopsy will be performed at Week 12. This study will utilize an\nexternal Data Monitoring Committee for the duration of the study to assess safety data.

• REC name

  South West - Central Bristol Research Ethics Committee

• REC reference

  20/SW/0164

• Date of REC Opinion

  11 Jan 2021

• REC opinion

  Further Information Favourable Opinion