Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Participants With Nonalcoholic Steatohepatitis (NASH)
Condition: Nonalcoholic Steatohepatitis
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease
Intervention: Semaglutide; Firsocostat; Cilofexor
Intervention description: Solution administered subcutaneously with pre-filled PDS290 pen-injector once weekly; Tablets administered orally once daily; Tablets administered orally once daily
Intervention MeSH terms: Firsocostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 109.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to evaluate the safety and tolerability of study
      drug(s) in participants with nonalcoholic steatohepatitis (NASH).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Historical liver biopsy consistent with NASH with stage 2-3 fibrosis according to NASH
             Clinical Research Network (CRN) classification OR clinical diagnosis of nonalcoholic
             fatty liver disease and screening FibroTest, magnetic resonance imaging - proton
             density fat fraction (MRI-PDFF), and FibroScan

          -  Screening laboratory parameters, as determined by central laboratory:

               -  Alanine aminotransferase (ALT) ≤ 5 x upper limit of the normal range (ULN)

               -  Estimated glomerular filtration rate (eGFR) ≥ 30 milliliter/minute (mL/min), as
                  calculated by the Modification of Diet in Renal Disease (MDRD) study equation

               -  HbA1c ≤ 9.5%

               -  International normalized ratio (INR) ≤ 1.2, unless due to therapeutic
                  anti-coagulation therapy

               -  Platelet count ≥ 100,000/μL

               -  Total bilirubin < 1.3 x ULN unless alternate etiology such as Gilbert's syndrome
                  present

               -  Calcitonin ≤ 100 ng/L

          -  Body Mass Index (BMI) > 23 kg/m^2 and body weight of > 60 kg

        Key Exclusion Criteria:

          -  Any historical liver biopsy consistent with cirrhosis

          -  Any history of decompensated liver disease, including ascites, hepatic encephalopathy,
             or variceal bleeding

          -  Other causes of liver disease, including but not limited to: alcoholic liver disease,
             hepatitis B, hepatitis C, autoimmune disorders (eg, primary biliary cholangitis (PBC),
             primary sclerosing cholangitis (PSC), autoimmune hepatitis), drug-induced
             hepatotoxicity, Wilson disease, clinically significant iron overload, or
             alpha-1-antitrypsin deficiency requiring treatment

          -  History of liver transplantation

          -  History of hepatocellular carcinoma

          -  History of pancreatitis (acute or chronic)

          -  Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or
             medullary thyroid carcinoma

          -  Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RA) in the period from
             90 days prior to the date of the Screening Visit

          -  Individuals on antidiabetic medications must be on a stable dose for at least 90 days
             prior to the date of the Screening Visit and in the period between the date of the
             Screening Visit and Enrollment (Day -14)

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.