Study to Evaluate the Safety and Efficacy of Selonsertib, Firsocostat, Cilofexor, and Combinations in Participants With Bridging Fibrosis or Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)
Condition: Nonalcoholic Steatohepatitis
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease
Intervention: SEL; FIR; CILO; Placebo to match FIR; Placebo to match CILO; Placebo to match SEL
Intervention description: 18 mg tablet administered orally once daily without regard to food; 20 mg tablet administered orally once daily without regard to food; 30 mg tablet administered orally once daily without regard to food; Tablet administered orally once daily without regard to food; Tablet administered orally once daily without regard to food; Tablet administered orally once daily without regard to food
Intervention MeSH terms: Firsocostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 395.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The primary objectives of this study are:

        -  To assess the safety and tolerability of selonsertib (SEL), firsocostat (FIR) and
           cilofexor (CILO), administered alone or in combination, in participants with bridging
           fibrosis or compensated cirrhosis due to NASH

        -  To evaluate changes in liver fibrosis, without worsening of NASH
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Liver biopsy consistent with NASH and F3 or F4 in the opinion of the central reader

          -  In participants who have never had a liver biopsy, liver stiffness by FibroScan® ≥
             14.0 kPa and Enhanced Liver Fibrosis (ELF™) Test score ≥ 9.8 at Screening

          -  Screening laboratory parameters, as determined by the central laboratory:

               -  Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, as calculated by the
                  Cockcroft-Gault equation

               -  Hemoglobin A1c (HbA1c) ≤ 9.5%

               -  Alanine aminotransferase (ALT) < 5 x Upper Limits of Normal (ULN)

               -  Platelet count ≥ 125,000/μL

        Key Exclusion Criteria:

          -  Prior history of decompensated liver disease including ascites, hepatic
             encephalopathy, or variceal bleeding

          -  Child-Pugh (CP) score > 6 at Screening, unless due to an alternative etiology such as
             Gilbert's syndrome or therapeutic anticoagulation

          -  Model for End-Stage Liver Disease (MELD) score > 12 at Screening, unless due to an
             alternate etiology such as therapeutic anticoagulation

          -  Other causes of liver disease based on medical history and/or centralized review of
             liver histology, including but not limited to: alcoholic liver disease, hepatitis B,
             hepatitis C, autoimmune disorders (eg, primary biliary cholangitis, primary sclerosing
             cholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease,
             clinically significant iron overload, or alpha-1-antitrypsin deficiency requiring
             treatment

          -  History of liver transplantation

          -  Current or prior history of hepatocellular carcinoma

        Note: Other protocol defined Inclusion/ Exclusion criteria may apply