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)

JRCT ID: jRCT2071210112

Registered date:19/01/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Nonalcoholic Steatohepatitis
• Date of first enrollment: 07/04/2022
• Target sample size: 440
• Countries of recruitment: US,Japan,Canada,Japan,France,Japan,Spain,Japan,Puerto Rico,Japan,Australia,Japan
• Study type: Interventional

Intervention(s)

Experimental: SEMA + CILO/FIR FDC
Participants will receive semaglutide (SEMA) 0.24-2.4 mg once weekly as subcutaneous (SC) injection (dose escalation every 4 weeks) and fixed-dose combination (FDC) tablet of cilofexor and firsocostat (CILO/FIR 30 mg/20 mg) once daily as orally for 72 weeks

Experimental: SEMA + Placebo-To-Match (PTM) CILO/FIR
Participants will receive SEMA 0.24-2.4 mg once weekly (dose escalation every 4 weeks) and PTM CILO/FIR administered once daily for 72 weeks

Experimental: PTM SEMA + CILO/FIR FDC
PTM Semaglutide once weekly and CILO/FIR 30 mg/20 mg FDC administered once daily for 72 weeks

Placebo Comparator: PTM SEMA + PTM CILO/FIR
PTM Semaglutide once weekly and PTM CILO/FIR once daily for 72 weeks

Outcome(s)

Primary Outcome

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
Worsening of NASH is defined as a >= 1-point increase in hepatocellular ballooning or lobular inflammation. [Time Frame: Week 72]
2. Percentage of Participants With NASH Resolution in Participants Treated with SEMA + CILO/FIR Versus Placebo
NASH resolution is defined as lobular inflammation of 0 or 1 and hepatocellular ballooning of 0. [Time Frame: Week 72]

Secondary Outcome

1.Percentage of Participants With NASH Resolution In Participants Treated With SEMA+CILO/FIR Versus CILO/FIR Alone [Time Frame: Week 72]
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]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 80age old
• Gender: Both

Include criteria

- 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

Exclude 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 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

Related Information

• Primary Sponsor: Kamiya Makoto
• Secondary ID(s): NCT04971785,2021-001445-12