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)
- Conditions
- Nonalcoholic Steatohepatitis
- Interventions
- Drug: SELDrug: FIRDrug: CILODrug: Placebo to match FIRDrug: Placebo to match CILODrug: Placebo to match SEL
- Registration Number
- NCT03449446
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 395
-
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
Key
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Selonsertib (SEL) 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. Selonsertib (SEL) Placebo to match FIR Participants will receive SEL + placebo to match firsocostat 20 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily for 48 weeks. Selonsertib (SEL) Placebo to match CILO Participants will receive SEL + placebo to match firsocostat 20 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily for 48 weeks. Firsocostat (FIR) 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. Firsocostat (FIR) Placebo to match CILO Participants will receive placebo to match SEL 18 mg tablet + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks. Firsocostat (FIR) Placebo to match SEL Participants will receive placebo to match SEL 18 mg tablet + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks. Cilofexor (CILO) 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. Cilofexor (CILO) Placebo to match FIR Participants will receive placebo to match SEL 18 mg tablet + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks. Cilofexor (CILO) Placebo to match SEL Participants will receive placebo to match SEL 18 mg tablet + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks. Selonsertib (SEL) + Firsocostat (FIR) SEL Participants will receive SEL + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks. Selonsertib (SEL) + Firsocostat (FIR) FIR Participants will receive SEL + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks. Selonsertib (SEL) + Firsocostat (FIR) Placebo to match CILO Participants will receive SEL + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks. Selonsertib (SEL) + Cilofexor (CILO) SEL Participants will receive SEL + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks. Selonsertib (SEL) + Cilofexor (CILO) CILO Participants will receive SEL + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks. Selonsertib (SEL) + Cilofexor (CILO) Placebo to match FIR Participants will receive SEL + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks. Firsocostat (FIR) + Cilofexor (CILO) FIR Participants will receive placebo to match SEL 18 mg tablet + FIR + CILO orally once daily for 48 weeks. Firsocostat (FIR) + Cilofexor (CILO) CILO Participants will receive placebo to match SEL 18 mg tablet + FIR + CILO orally once daily for 48 weeks. Firsocostat (FIR) + Cilofexor (CILO) Placebo to match SEL Participants will receive placebo to match SEL 18 mg tablet + FIR + CILO orally once daily for 48 weeks. Placebo Placebo to match FIR 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. Placebo Placebo to match CILO 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. Placebo Placebo to match SEL 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) First dose date up to 48 weeks plus 30 days Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities First dose date up to 48 weeks plus 30 days Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. Participants with any laboratory abnormality were reported.
Percentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at Week 48 Week 48 Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH clinical research network classification (CRN) classification. Worsening of NASH was defined as ≥ 1-point increase from baseline in hepatocellular ballooning or lobular inflammation. The 95% CI was based on the Clopper-Pearson method.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (101)
Ruane Clinical Research Group Inc.
🇺🇸Los Angeles, California, United States
Piedmont Hospital
🇺🇸Atlanta, Georgia, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Northwestern University; Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Louisiana Research Center, LLC
🇺🇸Shreveport, Louisiana, United States
Rutgers New Jersey Medical School- Doctors Office Center
🇺🇸Newark, New Jersey, United States
Hospital of the University of Pennsylvania- Perelman Center for Advanced Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Royal Brisbane & Women's Hospital
🇦🇺Herston, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Southern California Liver Center
🇺🇸Coronado, California, United States
Iowa Digestive Disease Center, P.C.
🇺🇸Clive, Iowa, United States
Integrity Clinical Research
🇺🇸Doral, Florida, United States
Southern Therapy and Advanced Research (STAR) LLC
🇺🇸Ridgeland, Mississippi, United States
South Denver Gastroenterology, PC
🇺🇸Englewood, Colorado, United States
Gastrointestinal Specialists of Georgia
🇺🇸Marietta, Georgia, United States
Carolinas Healthcare System Center for Liver Disease and Transplant
🇺🇸Charlotte, North Carolina, United States
Cumberland Research Associates, LLC
🇺🇸Fayetteville, North Carolina, United States
Fresno Clinical Research Center
🇺🇸Fresno, California, United States
eStudySite
🇺🇸Chula Vista, California, United States
Inland Empire Liver Foundation
🇺🇸Rialto, California, United States
Gastrointestinal Diseases Research
🇺🇸Columbus, Georgia, United States
Delta Research Partners, LLC
🇺🇸Bastrop, Louisiana, United States
Digestive Disease Associates, PA
🇺🇸Catonsville, Maryland, United States
Texas Clinical Research Institute, LLC
🇺🇸Arlington, Texas, United States
Pinnacle Clinical Research
🇺🇸Live Oak, Texas, United States
Westmead Hospital
🇦🇺Westmead, Australia
California Pacific Medical Center - Sutter Pacific Medical Foundation San Francisco Center for Liver Disease Dept. of Transplant
🇺🇸Falls Church, Virginia, United States
Concorde Medical Group, PLLC
🇺🇸New York, New York, United States
NYU Langone Health
🇺🇸New York, New York, United States
VA Pittsburgh Healthcare System
🇺🇸Pittsburgh, Pennsylvania, United States
GHS Gastroenterology and Liver Center
🇺🇸Greenville, South Carolina, United States
Gastro One
🇺🇸Germantown, Tennessee, United States
St Vincent's Hospital Sydney
🇦🇺Darlinghurst, Australia
Auckland City Hospital
🇳🇿Auckland, New Zealand
UPMC - Center for Liver Diseases at the Thomas E. Starlz Institute
🇺🇸Pittsburgh, Pennsylvania, United States
University of Virginia Medical Center
🇺🇸Charlottesville, Virginia, United States
Digestive and Liver Disease Specialists
🇺🇸Norfolk, Virginia, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Austin Health
🇦🇺Heidelberg, Australia
William Osler Health System-Brampton Civic Hospital
🇨🇦Brampton, Canada
University of Calgary Liver Unit (Heritage Medical Research Clinic)
🇨🇦Calgary, Canada
The Liver Institute at Methodist Dallas Medical Center
🇺🇸Dallas, Texas, United States
St Vincent's Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
Intermountain Liver Disease and Transplant Center
🇺🇸Murray, Utah, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, Australia
Chronic Viral Illness Service McGill University Health Centre (MUHC)/ Royal Victoria Hospital
🇨🇦Montreal, Canada
Medical Associates Research Group
🇺🇸San Diego, California, United States
Schiff Center for Liver Diseases/University of Miami
🇺🇸Miami, Florida, United States
IMIC Inc
🇺🇸Miami, Florida, United States
Genoma Research Group
🇺🇸Miami, Florida, United States
Indianapolis Gastroenterology Research Foundation
🇺🇸Indianapolis, Indiana, United States
Jubilee Clinical Research, Inc.
🇺🇸Las Vegas, Nevada, United States
Duke University Medical Center, Duke South Clinics
🇺🇸Durham, North Carolina, United States
Quality Medical Research, PLLC
🇺🇸Nashville, Tennessee, United States
Consultants for Clinical Research wed
🇺🇸Cincinnati, Ohio, United States
Baylor College of Medicine - Advanced Liver Therapies
🇺🇸Houston, Texas, United States
American Research Corporation at Texas Liver Institute
🇺🇸San Antonio, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
University of Utah Hospital
🇺🇸Salt Lake City, Utah, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Swedish Organ Transplant and Liver Center
🇺🇸Seattle, Washington, United States
Royal Perth Hospital
🇦🇺Perth, Western Australia, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Mayo Clinic Arizona, Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
Henry Ford Health Systems
🇺🇸Detroit, Michigan, United States
Toronto General Hospital
🇨🇦Toronto, Canada
The Alfred Hospital, Alfred Health
🇦🇺Melbourne, Australia
Icahn School of Medicine at Mount Sinai Beth Israel
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
UCSD NAFLD Clinical Research Center
🇺🇸La Jolla, California, United States
California Liver Research Institute
🇺🇸Pasadena, California, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Monash Health, Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Liver Wellness Center
🇺🇸Little Rock, Arkansas, United States
Digestive Healthcare of Georgia
🇺🇸Atlanta, Georgia, United States
The Institute for Liver Health
🇺🇸Chandler, Arizona, United States
Arkansas Gastroenterology
🇺🇸North Little Rock, Arkansas, United States
Huntington Medical Research Institutes Liver Center
🇺🇸Pasadena, California, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
Sandra Atlas Bass Center for Liver Diseases and Transplantation
🇺🇸Manhasset, New York, United States
University of Texas Southwestern Medical Center Internal Medicine Digestive and Liver Diseases Clinical Trials
🇺🇸Dallas, Texas, United States
University Gastroenterology
🇺🇸Providence, Rhode Island, United States
Toronto Liver Centre
🇨🇦Toronto, Canada
Fundacion de Investigacion de Diego
🇵🇷San Juan, Puerto Rico
University of California, Davis Medical Center (study visits)
🇺🇸Sacramento, California, United States
UF Hepatology Research at CTRB
🇺🇸Gainesville, Florida, United States
Florida Research Institute
🇺🇸Tampa, Florida, United States
Tulane University
🇺🇸New Orleans, Louisiana, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Medical University of South Carolina (Liver Biopsy)
🇺🇸Charleston, South Carolina, United States
Pinnacle Clinical Research, PLLC
🇺🇸Austin, Texas, United States
Austin Center for Clinical Research
🇺🇸Austin, Texas, United States
Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond
🇺🇸Richmond, Virginia, United States
McGuire DVAMC
🇺🇸Richmond, Virginia, United States
Melbourne Health, Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Prince of Wales Hospital
🇭🇰Shatin, Hong Kong