Study of Semaglutide, and Cilofexor/Firsocostat, Alone and in Combination, in Adults With Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)

Not Recruiting

Trial ID: NCT04971785

Purpose

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.

Official Title

A Phase 2, Randomized, Double-Blind, Double-Dummy, Placebo-Controlled Study Evaluating the Safety and Efficacy of Semaglutide, and the Fixed-Dose Combination of Cilofexor and Firsocostat, Alone and in Combination, in Subjects With Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)

Stanford Investigator(s)

Paul Kwo
Paul Kwo

Professor of Medicine (Gastroenterology and Hepatology)

Eligibility

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.

Intervention(s):

drug: Semaglutide (SEMA)

drug: Cilofexor (CILO)/Firsocostat (FIR)

drug: PTM SEMA

drug: PTM CILO/FIR

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Jennifer Smart
650-721-8517