Vanderbilt Clinical Trials

Study to Evaluate the Safety and Efficacy of Selonsertib, Firsocostat, Cilofexor, and Combinations in Participants With Bridging Fibrosis or Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH)

Purpose

The primary objectives of this study are: - To assess the safety and tolerability of selonsertib (SEL), firsocostat (FIR) and cilofexor (CILO), administered alone or in combination, in participants with bridging fibrosis or compensated cirrhosis due to NASH - To evaluate changes in liver fibrosis, without worsening of NASH

Condition

Nonalcoholic Steatohepatitis

Eligibility

Eligible Ages: Between 18 Years and 80 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Liver biopsy consistent with NASH and F3 or F4 in the opinion of the central reader - In participants who have never had a liver biopsy, liver stiffness by FibroScan® ≥ 14.0 kPa and Enhanced Liver Fibrosis (ELF™) Test score ≥ 9.8 at Screening - Screening laboratory parameters, as determined by the central laboratory: - Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, as calculated by the Cockcroft-Gault equation - Hemoglobin A1c (HbA1c) ≤ 9.5% - Alanine aminotransferase (ALT) < 5 x Upper Limits of Normal (ULN) - Platelet count ≥ 125,000/μL

Exclusion Criteria

Prior history of decompensated liver disease including ascites, hepatic encephalopathy, 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 alternate etiology such as therapeutic anticoagulation - Other causes of liver disease based on medical history and/or centralized review of liver histology, including but not limited to: alcoholic liver disease, hepatitis B, hepatitis C, 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 requiring treatment - History of liver transplantation - Current or prior history of hepatocellular carcinoma Note: Other protocol defined Inclusion/ Exclusion criteria may apply

Study Design

Phase: Phase 2
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: Double (Participant, Investigator)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Selonsertib (SEL)	Participants will receive SEL + placebo to match firsocostat 20 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily for 48 weeks.	Drug: SEL 18 mg tablet administered orally once daily without regard to food Drug: Placebo to match FIR Tablet administered orally once daily without regard to food Drug: Placebo to match CILO Tablet administered orally once daily without regard to food
Experimental Firsocostat (FIR)	Participants will receive placebo to match SEL 18 mg tablet + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.	Drug: FIR 20 mg tablet administered orally once daily without regard to food Other names: GS-0976 Drug: Placebo to match CILO Tablet administered orally once daily without regard to food Drug: Placebo to match SEL Tablet administered orally once daily without regard to food
Experimental Cilofexor (CILO)	Participants will receive placebo to match SEL 18 mg tablet + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.	Drug: CILO 30 mg tablet administered orally once daily without regard to food Other names: GS-9674 Drug: Placebo to match FIR Tablet administered orally once daily without regard to food Drug: Placebo to match SEL Tablet administered orally once daily without regard to food
Experimental Selonsertib (SEL) + Firsocostat (FIR)	Participants will receive SEL + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.	Drug: SEL 18 mg tablet administered orally once daily without regard to food Drug: FIR 20 mg tablet administered orally once daily without regard to food Other names: GS-0976 Drug: Placebo to match CILO Tablet administered orally once daily without regard to food
Experimental Selonsertib (SEL) + Cilofexor (CILO)	Participants will receive SEL + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.	Drug: SEL 18 mg tablet administered orally once daily without regard to food Drug: CILO 30 mg tablet administered orally once daily without regard to food Other names: GS-9674 Drug: Placebo to match FIR Tablet administered orally once daily without regard to food
Experimental Firsocostat (FIR) + Cilofexor (CILO)	Participants will receive placebo to match SEL 18 mg tablet + FIR + CILO orally once daily for 48 weeks.	Drug: FIR 20 mg tablet administered orally once daily without regard to food Other names: GS-0976 Drug: CILO 30 mg tablet administered orally once daily without regard to food Other names: GS-9674 Drug: Placebo to match SEL Tablet administered orally once daily without regard to food
Experimental Placebo	Participants will receive placebo to match SEL 18 mg + placebo to match FIR 20 mg tablet + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.	Drug: Placebo to match FIR Tablet administered orally once daily without regard to food Drug: Placebo to match CILO Tablet administered orally once daily without regard to food Drug: Placebo to match SEL Tablet administered orally once daily without regard to food

More Details

Status: Completed
Sponsor: Gilead Sciences

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.