study of semaglutide, and cilofexor/firsocostat, alone and in combination, in adults with cirrhosis due to nonalcoholic steatohepatitis (nash)

Conditions: Nonalcoholic Steatohepatitis

Summary: the goals of this clinical study are to learn more about the study drugs, semaglutide (sema) with the fixed-dose combination (fdc) of cilofexor/firsocostat (cilo/fir), and understand whether they cause fibrosis improvement and nonalcoholic steatohepatitis (nash) resolution in participants with cirrhosis due to nash.


Eligibility criteria:
key inclusion criteria: * liver biopsy consistent with cirrhosis (f4) due to nonalcoholic steatohepatitis (nash) in the opinion of the central reader. in individuals 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% * international normalized ratio (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 * body mass index (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 hepatitis b virus (hbv) infection (hbsag positive), or chronic hepatitis c virus (hcv) infection (hcv antibody and hcv ribonucleic acid (rna) positive). individuals 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 (1 unit is equivalent to 12 ounce (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 individuals who have not completed a series of an authorized coronavirus disease 2019 (covid-19) vaccination regimen prior to screening, a positive result for covid-19 on severe acute respiratory syndrome coronavirus 2 (sars-cov-2) reverse transcriptase-polymerase chain reaction (rt-pcr) test. note: other protocol defined inclusion/exclusion criteria may apply.