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)

Overview

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Manal Abdelmalek, M.D.

Closed for enrollment

Contact information:

Marina Takawy M.B., B.Ch.

(507) 293-0913

Takawy.Marina@mayo.edu

More information

Publications

Publications are currently not available
.
CLS-20544036

Mayo Clinic Footer