A Phase 2B Randomized Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of BMS-986036 (PEG-FGF21) in Adults With Nonalcoholic Steatohepatitis (NASH) and Stage 3 Liver Fibrosis
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 197
- Locations
- 89
- Primary Endpoint
- The Percentage of Participants With Improvement in Fibrosis or Nonalcoholic Steatohepatitis (NASH) at Week 24
Study Overview
Brief Summary
This is a study of experimental medication BMS-986036 given to adults with Nonalcoholic Steatohepatitis (NASH; the buildup of fat and inflammation in the liver that is not caused by alcohol) and stage 3 liver fibrosis (severe fibrosis).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Liver biopsy performed within 6 months (26 weeks) prior to the screening period. If historical biopsy is not available, a liver biopsy will be performed during the screening period. Biopsy must be consistent with NASH, with: a) a score of at least 1 for each NAS component (steatosis, lobular inflammation, and ballooning), as assessed by the central reader, and b) stage 3 liver fibrosis according to the NASH CRN classification, as assessed by the central reader
- •Participants taking anti-diabetic, anti-obesity, or anti-dyslipidemic medications must have been on stable regimens for at least 3 months (12 weeks) (6 weeks for statins) prior to and during the screening period
- •Participants taking vitamin E at doses greater than or equal to (>=) 800 IU/day must have been on stable doses for at least 6 months (26 weeks) prior to and during the Screening Period. Vitamin E treatment (>=800 IU/day) must not have been initiated after the qualifying liver biopsy was performed.
Exclusion Criteria
- •Other causes of liver disease (e.g., alcoholic liver disease, hepatitis B virus infection, chronic hepatitis C virus [HCV] infection, autoimmune hepatitis, drug-induced hepatotoxicity, Wilson disease, α-1-antitrypsin deficiency, iron overload, and hemochromatosis); participants with HCV sustained viral response (undetectable HCV RNA) for at least 2 years prior to biopsy confirming study eligibility may be eligible
- •Current or past history of hepatocellular carcinoma (HCC)
- •Past or current evidence of hepatic decompensation (e.g., ascites, variceal bleeding, hepatic encephalopathy and/or spontaneous bacterial peritonitis) or liver transplantation
- •Other protocol defined inclusion/exclusion criteria could apply
Arms & Interventions
BMS-986036 Dose Level 1
Administered by subcutaneous injection.
Intervention: BMS-986036 (Drug)
BMS-986036 Dose Level 2
Administered by subcutaneous injection.
Intervention: BMS-986036 (Drug)
BMS-986036 Dose Level 3
Administered by subcutaneous injection.
Intervention: BMS-986036 (Drug)
Placebo
Administered by subcutaneous injection.
Intervention: Placebo (Other)
Outcomes
Primary Outcomes
The Percentage of Participants With Improvement in Fibrosis or Nonalcoholic Steatohepatitis (NASH) at Week 24
Time Frame: From first dose to 24 weeks after first dose
The percentage of participants who achieved a ≥1-stage improvement in fibrosis without worsening of NASH or NASH improvement with no worsening of fibrosis at week 24 in liver biopsy. Improvement in fibrosis is defined by the NASH Clinical Research Network (CRN) Fibrosis Score. Improvement in NASH is defined by a ≥2-stage decrease in the nonalcoholic fatty liver disease activity score (NAS). Worsening of NASH is defined as an increase of the nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) by ≥1 point. Worsening of fibrosis is defined as an increase of fibrosis by ≥1 point as determined by the NASH CRN Fibrosis Score. NASH CRN Fibrosis is staged on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal fibrosis); 2 (perisinusoidal and portal/periportal fibrosis); 3 (bridging fibrosis); 4 (cirrhosis).
Secondary Outcomes
- The Percentage of Participants Who Achieved an Improvement in Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Score at Week 24(From first dose to 24 weeks after first dose)
- The Percentage of Participants Who Achieve a ≥ 1-Stage Improvement in Ishak Fibrosis Score at Week 24(From first dose to 24 weeks after first dose)
- The Percentage of Participants With Any Improvement in Collagen Proportionate Area (CPA) at Week 24(From first dose to 24 weeks after first dose)
- The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis at Week 24(From first dose to 24 weeks after first dose)
- The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Resolution at Week 24(From first dose to 24 weeks after first dose)
- The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Improvement Without Worsening of Fibrosis at Week 24(From first dose to 24 weeks after first dose)
- The Percentage of Participants Who Achieve a ≥ 1-Stage Improvement in Fibrosis Without Worsening of Nonalcoholic Steatohepatitis (NASH) at Week 24(From first dose to 24 weeks after first dose)
- The Percentage of Participants With Nonalcoholic Steatohepatitis (NASH) Improvement at Week 24(From first dose to 24 weeks after first dose)
- The Percentage of Participants With Progression to Cirrhosis at Week 24(From first dose to 24 weeks after first dose)