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)
- Conditions
- onalcoholic Steatohepatitis
- Registration Number
- JPRN-jRCT2071210112
- Lead Sponsor
- Kamiya Makoto
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 440
Liver biopsy consistent with cirrhosis (F4) due to NASH in the opinion of the central reader.
- Screening laboratory parameters as determined by the study central laboratory:
- Estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73m2, 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/ m2 at screening
- 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 Gilberts 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Percentage of Participants Who Achieve >= 1-Stage Improvement in Fibrosis According to the NASH Clinical Research Network (CRN) Classification Without Worsening of NASH in Participants Treated With SEMA + CILO/FIR Versus Placebo<br>Worsening of NASH is defined as a >= 1-point increase in hepatocellular ballooning or lobular inflammation. [Time Frame: Week 72]<br>2. Percentage of Participants With NASH Resolution in Participants Treated with SEMA + CILO/FIR Versus Placebo <br>NASH resolution is defined as lobular inflammation of 0 or 1 and hepatocellular ballooning of 0. [Time Frame: Week 72]
- Secondary Outcome Measures
Name Time Method 1.Percentage of Participants With NASH Resolution In Participants Treated With SEMA+CILO/FIR Versus CILO/FIR Alone [Time Frame: Week 72]<br>2. Percentage of Participants Who Achieve >= 1-Stage Improvement in Fibrosis (According to the NASH CRN Classification) Without Worsening of NASH in Participants Treated With SEMA+CILO/FIR Versus SEMA Alone Worsening of NASH is defined as a >= 1-point increase in hepatocellular ballooning or lobular inflammation. [Time Frame: Week 72]