Liver Fibrosis, Nonalcoholic Fatty Liver Disease (NAFLD), Nonalcoholic Steatohepatitis
Conditions
Sponsors
Bristol-Myers Squibb K.K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Liver biopsy performed within 6 months prior to the Screening Visit; if not performed within 6 months prior to the Screening Visit, a liver biopsy will be performed during the Screening Period and at least 4 weeks prior to randomization. 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 dosing regimens for at least 3 months prior to the Screening Visit Participants taking vitamin E at doses more than 800 IU/day must have been on stable doses for at least 6 months prior to the Screening Visit (Vitamin E treatment must not have been initiated after the liver biopsy was performed) Other protocol defined inclusion criteria could apply
Exclusion criteria
Exclusion criteria: Other causes of liver disease (e.g., alcoholic liver disease, hepatitis B virus infection, chronic hepatitis C virus infection, autoimmune hepatitis, drug-induced hepatotoxicity, Wilson disease, alpha-1-antitrypsin deficiency, iron overload, and hemochromatosis) 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 exclusion criteria could apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Proportion of participants who achieve more than 1 stage improvement in fibrosis without worsening of NASH or NASH improvement with no worsening of fibrosis as determined by liver biopsy [Time Frame: 24 weeks] NASH Clinical Research Network (CRN) Fibrosis Score [Fibrosis measured on a 0-4 scale: 0 (none); 1 (perisinusoidal or periportal); 2 (perisinusoidal and portal/periportal); 3 (bridging fibrosis); 4 (cirrhosis)] [Time Frame: 24 weeks]NAFLD Activity Score (NAS) [NASH disease activity in the liver measured on a 0-8 scale: unweighted sum of steatosis, or fat (scale: 0-3), lobular inflammation (scale: 0-3), and hepatocellular ballooning (scale: 0-2)] [Time Frame: 24 weeks] | — |
Secondary
| Measure | Time frame |
|---|---|
| safety efficacy exploratory pharmacokinetics pharmacodynamics pharmacogenomics Proportion of participants with NASH CRN Fibrosis Score improvement as determined by liver biopsy [Time Frame: 24 weeks] Proportion of participants with Ishak Score improvement as determined by liver biopsy [Time Frame: 24 weeks] Proportion of participants with a decrease in collagen proportionate area (CPA) as determined by liver biopsy [Time Frame: 24 weeks] Proportion of participants with NASH resolution without worsening of fibrosis as determined by liver biopsy [Time Frame: 24 weeks] Proportion of participants with NASH resolution as determined by liver biopsy [Time Frame: 24 weeks] Proportion of participants with NASH improvement without worsening of fibrosis as determined by liver biopsy [Time Frame: 24 weeks] Proportion of participants with NASH improvement as determined by liver biopsy [Time Frame: 24 weeks] Proportion of participants with progression to cirrhosis, as determined by liver biopsy [Time Frame: 24 weeks] Incidence of adverse events (AE) [Time Frame: Up to 52 weeks] | — |
Countries
Japan, North America
Outcome results
None listed