Study Evaluating the Safety and Efficacy of Semaglutide, and the Fixed-Dose Combination of Cilofexor and Firsocostat, Alone and in Combination, in Participants With Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)

• Status: Recruiting
• Trial end date: 2024-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to evaluate whether the combination of semaglutide (SEMA) with the fixed-dose combination (FDC) of cilofexor/firsocostat (CILO/FIR) causes fibrosis improvement and Nonalcoholic Steatohepatitis (NASH) resolution in participants with compensated cirrhosis due to NASH.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gilead Sciences
• Collaborator: Novo Nordisk A/S
• Treatments: Firsocostat

Criteria

Key Inclusion Criteria:

• Liver biopsy consistent with cirrhosis (F4) due to NASH in the opinion of the central reader. In participants who have never had a liver biopsy, a screening liver biopsy may be performed

• Screening laboratory parameters as determined by the study central laboratory:

• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m^2, as calculated by the Modification of Diet in Renal Disease (MDRD) equation

• HbA1c ≤ 10%

• INR ≤ 1.4, unless due to therapeutic anticoagulation

• Platelet count ≥ 125,000/uL

• Alanine Aminotransferase (ALT) < 5 x ULN

• Serum albumin ≥ 3.5 g/dL

• Serum Alkaline Phosphatase (ALP) ≤ 2 x ULN

• BMI ≥ 23 kg/m^2 at screening

Key Exclusion Criteria:

• Prior history of decompensated liver disease, including ascites, hepatic encephalopathy (HE), 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 alternative etiology such as therapeutic anticoagulation

• Other causes of liver disease based on medical history and/or central reader review of liver histology, including but not limited to: alcoholic liver disease, 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

• Chronic HBV infection (HBsAg positive), or Chronic HCV infection (HCV antibody and HCV RNA positive). Participants cured of HCV infection less than 2 years prior to the screening visit are not eligible

• History of liver transplantation

• Current or prior history of hepatocellular carcinoma (HCC)

• Men who habitually drink greater than 21 units/week of alcohol or women who habitually drink greater than 14 units/week of alcohol (one unit is equivalent to 12 oz/360 mL of beer, a 4 oz/120 mL glass of wine, or 1 oz/30 mL of hard liquor).

• For individuals on vitamin E regimen ≥ 800 IU/day, or pioglitazone, dose must be stable, in the opinion of the investigator for at least 180 days prior to the historical or screening liver biopsy

• For individuals on medications for diabetes, dose must be stable, in the opinion of the investigator, for at least 90 days prior to the historical or screening liver biopsy

• History of type 1 diabetes

• Treatment with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in the period from 90 days prior to the screening visit and for individuals with a qualifying historical liver biopsy, for 90 days prior to the date of the historical liver biopsy

• For participants who have not completed a series of an authorized COVID-19 vaccination regimen prior to screening, a positive result for COVID-19 on SARS-CoV-2 RT-PCR test

Note: Other protocol defined Inclusion/Exclusion criteria may apply.