Nonalcoholic Steatohepatitis
Conditions
Interventions
Patients who have completed screening procedures (up to 56 days duration) and
met inclusion/exclusion criteria will be randomized on Day 1 of the treatment
period.
Patients will be randomized in a 1
Sponsors
Bristol-Myers Squibb
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: *Male and female participants, ages >= 21 years to = 30 kg/m2 (ii) History of type 2 diabetes mellitus (iii) History of hypertension AND/OR history of dyslipidemia OR (b) Previous histologic readings of steatohepatitis (for biopsies > 12 months prior to screening visit) AND either history of BMI >= 30 kg/m2 OR history of type 2 diabetes mellitus. NOTE: At least 80% of participants will be required to have definite steatohepatitis on the biopsy used to confirm eligibility.
Exclusion criteria
Exclusion criteria: *Other active causes of liver disease (eg, alcoholic liver disease, hepatitis B virus infection, chronic hepatitis C virus infection, autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, drug-induced hepatotoxicity, Wilson disease, homozygous a-1- antitrypsin deficiency, iron overload [with blood iron saturation > 50%], or hemochromatosis) * Past or current evidence of hepatic decompensation (eg, ascites, variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis) * Liver transplantation (past or planned) * Child-Pugh Score > 6 at screening. Participants with a Child-Pugh Score > 6 with elevated total bilirubin and who have Gilbert Syndrome and direct bilirubin 14 at screening. Participants with a MELD Score > 14 with elevated total bilirubin and who have Gilbert Syndrome and direct bilirubin 20 ng/mL (> 16.5 IU/mL) or (ii) Liver Reporting & Data System 3, 4, or 5 as determined by historical computed tomography (CT)/magnetic resonance imaging (MRI) within 3 months prior to screening or from multiphasic CT/MRI of liver during screening * The participant*s laboratory test results at screening include any of the following: * Albumin 2.2 * Alanine aminotransferase value >= 5× the ULN * Aspartate aminotransferase value >= 5× the ULN * Total bilirubin > 3.0 mg/dL, unless participant has a diagnosis of Gilbert Syndrome and direct bilirubin = 9.0% * Serum vitamin A (retinol) > ULN * Inability to safely undergo a liver biopsy in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the efficacy of BMS-986263 compared with placebo to improve liver fibrosis in participants with compensated cirrhosis due to NASH, by: Proportion of participants who achieve >= 1 stage improvement in liver fibrosis (NASH CRN Fibrosis Score), as determined by liver biopsy after 12 weeks of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| To further assess the efficacy of BMS-986263 compared with placebo to improve liver fibrosis, as determined by liver biopsy, in participants with compensated cirrhosis due to NASH, by: * Proportion of participants with >= 1 stage improvement in liver fibrosis (NASH CRN Fibrosis Score), with no worsening of NASH after 12 weeks of treatment (worsening defined as an increase of the NAS by >= 1 point) * Proportion of participants with >= 2 stage improvement in liver fibrosis (NASH CRN Fibrosis Score) after 12 weeks of treatment Proportion of * Proportion of participants with >= 1 stage improvement in liver fibrosis (modified Ishak score) after 12 weeks of treatment * Proportion of participants with >= 2 stage improvement in liver fibrosis (modified Ishak score) after 12 weeks of treatment * Change from baseline in CPA after 12 weeks of treatment To assess the safety and tolerability of BMS-986263 in participants with compensated cirrhosis due to NASH, by: * Incidences of SAEs, AEs, clinical laboratory values, vital signs, physical examination findings, and ECGs * Change from baseline in BMD, as measured by DXA scan, at Follow-up Week 24 To assess the PK of BMS-986263 in participants with compensated cirrhosis due to NASH * Plasma concentrations of siRNA, DPD, HEDC, and S104 (components of BMS-986263 for injection) | — |
Countries
Netherlands
Outcome results
None listed