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)
NCT ID: NCT03449446
Last Updated: 2020-12-03
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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COMPLETED
PHASE2
395 participants
INTERVENTIONAL
2018-03-21
2019-11-19
Brief Summary
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* 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
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
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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.
SEL
18 mg tablet administered orally once daily without regard to food
Placebo to match FIR
Tablet administered orally once daily without regard to food
Placebo to match CILO
Tablet administered orally once daily without regard to food
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.
FIR
20 mg tablet administered orally once daily without regard to food
Placebo to match CILO
Tablet administered orally once daily without regard to food
Placebo to match SEL
Tablet administered orally once daily without regard to food
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.
CILO
30 mg tablet administered orally once daily without regard to food
Placebo to match FIR
Tablet administered orally once daily without regard to food
Placebo to match SEL
Tablet administered orally once daily without regard to food
Selonsertib (SEL) + Firsocostat (FIR)
Participants will receive SEL + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
SEL
18 mg tablet administered orally once daily without regard to food
FIR
20 mg tablet administered orally once daily without regard to food
Placebo to match CILO
Tablet administered orally once daily without regard to food
Selonsertib (SEL) + Cilofexor (CILO)
Participants will receive SEL + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.
SEL
18 mg tablet administered orally once daily without regard to food
CILO
30 mg tablet administered orally once daily without regard to food
Placebo to match FIR
Tablet administered orally once daily without regard to food
Firsocostat (FIR) + Cilofexor (CILO)
Participants will receive placebo to match SEL 18 mg tablet + FIR + CILO orally once daily for 48 weeks.
FIR
20 mg tablet administered orally once daily without regard to food
CILO
30 mg tablet administered orally once daily without regard to food
Placebo to match SEL
Tablet administered orally once daily without regard to food
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.
Placebo to match FIR
Tablet administered orally once daily without regard to food
Placebo to match CILO
Tablet administered orally once daily without regard to food
Placebo to match SEL
Tablet administered orally once daily without regard to food
Interventions
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SEL
18 mg tablet administered orally once daily without regard to food
FIR
20 mg tablet administered orally once daily without regard to food
CILO
30 mg tablet administered orally once daily without regard to food
Placebo to match FIR
Tablet administered orally once daily without regard to food
Placebo to match CILO
Tablet administered orally once daily without regard to food
Placebo to match SEL
Tablet administered orally once daily without regard to food
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* 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
18 Years
80 Years
ALL
No
Sponsors
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Gilead Sciences
INDUSTRY
Responsible Party
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Principal Investigators
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Gilead Study Director
Role: STUDY_DIRECTOR
Gilead Sciences
Locations
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The Institute for Liver Health
Chandler, Arizona, United States
Mayo Clinic Arizona, Mayo Clinic Hospital
Phoenix, Arizona, United States
Liver Wellness Center
Little Rock, Arkansas, United States
Arkansas Gastroenterology
North Little Rock, Arkansas, United States
eStudySite
Chula Vista, California, United States
Southern California Liver Center
Coronado, California, United States
Fresno Clinical Research Center
Fresno, California, United States
UCSD NAFLD Clinical Research Center
La Jolla, California, United States
Ruane Clinical Research Group Inc.
Los Angeles, California, United States
Cedars-Sinai Medical Center
Los Angeles, California, United States
California Liver Research Institute
Pasadena, California, United States
Huntington Medical Research Institutes Liver Center
Pasadena, California, United States
Inland Empire Liver Foundation
Rialto, California, United States
University of California, Davis Medical Center (study visits)
Sacramento, California, United States
Medical Associates Research Group
San Diego, California, United States
South Denver Gastroenterology, PC
Englewood, Colorado, United States
Integrity Clinical Research
Doral, Florida, United States
UF Hepatology Research at CTRB
Gainesville, Florida, 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
Florida Research Institute
Tampa, Florida, United States
Digestive Healthcare of Georgia
Atlanta, Georgia, United States
Piedmont Hospital
Atlanta, Georgia, United States
Gastrointestinal Diseases Research
Columbus, Georgia, United States
Gastrointestinal Specialists of Georgia
Marietta, Georgia, United States
Northwestern University; Feinberg School of Medicine
Chicago, Illinois, United States
Indianapolis Gastroenterology Research Foundation
Indianapolis, Indiana, United States
Iowa Digestive Disease Center, P.C.
Clive, Iowa, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
Delta Research Partners, LLC
Bastrop, Louisiana, United States
Tulane University
New Orleans, Louisiana, United States
Louisiana Research Center, LLC
Shreveport, Louisiana, United States
Mercy Medical Center
Baltimore, Maryland, United States
Digestive Disease Associates, PA
Catonsville, Maryland, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Henry Ford Health Systems
Detroit, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
Southern Therapy and Advanced Research (STAR) LLC
Ridgeland, Mississippi, United States
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, United States
Saint Louis University
St Louis, Missouri, United States
Jubilee Clinical Research, Inc.
Las Vegas, Nevada, United States
Rutgers New Jersey Medical School- Doctors Office Center
Newark, New Jersey, United States
Sandra Atlas Bass Center for Liver Diseases and Transplantation
Manhasset, New York, United States
Icahn School of Medicine at Mount Sinai Beth Israel
New York, New York, United States
Concorde Medical Group, PLLC
New York, New York, United States
NYU Langone Health
New York, New York, United States
Weill Cornell Medical College
New York, New York, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Montefiore Medical Center
The Bronx, New York, United States
Carolinas Healthcare System Center for Liver Disease and Transplant
Charlotte, North Carolina, United States
Duke University Medical Center, Duke South Clinics
Durham, North Carolina, United States
Cumberland Research Associates, LLC
Fayetteville, North Carolina, United States
Consultants for Clinical Research wed
Cincinnati, Ohio, United States
Hospital of the University of Pennsylvania- Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
UPMC - Center for Liver Diseases at the Thomas E. Starlz Institute
Pittsburgh, Pennsylvania, United States
VA Pittsburgh Healthcare System
Pittsburgh, Pennsylvania, United States
University Gastroenterology
Providence, Rhode Island, United States
Medical University of South Carolina (Liver Biopsy)
Charleston, South Carolina, United States
GHS Gastroenterology and Liver Center
Greenville, South Carolina, United States
Gastro One
Germantown, Tennessee, United States
Quality Medical Research, PLLC
Nashville, Tennessee, United States
Texas Clinical Research Institute, LLC
Arlington, Texas, United States
Pinnacle Clinical Research, PLLC
Austin, Texas, United States
Austin Center for Clinical Research
Austin, Texas, United States
The Liver Institute at Methodist Dallas Medical Center
Dallas, Texas, United States
University of Texas Southwestern Medical Center Internal Medicine Digestive and Liver Diseases Clinical Trials
Dallas, Texas, United States
Baylor College of Medicine - Advanced Liver Therapies
Houston, Texas, United States
Houston Methodist Hospital
Houston, Texas, United States
Pinnacle Clinical Research
Live Oak, Texas, United States
American Research Corporation at Texas Liver Institute
San Antonio, Texas, United States
Intermountain Liver Disease and Transplant Center
Murray, Utah, United States
University of Utah Hospital
Salt Lake City, Utah, United States
University of Virginia Medical Center
Charlottesville, Virginia, United States
California Pacific Medical Center - Sutter Pacific Medical Foundation San Francisco Center for Liver Disease Dept. of Transplant
Falls Church, Virginia, United States
Digestive and Liver Disease Specialists
Norfolk, Virginia, 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
Virginia Mason Medical Center
Seattle, Washington, United States
Swedish Organ Transplant and Liver Center
Seattle, Washington, United States
Royal Brisbane & Women's Hospital
Herston, Queensland, Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia
Monash Health, Monash Medical Centre
Clayton, Victoria, Australia
St Vincent's Hospital Melbourne
Fitzroy, Victoria, Australia
Melbourne Health, Royal Melbourne Hospital
Parkville, Victoria, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia
Royal Perth Hospital
Perth, Western Australia, Australia
Royal Prince Alfred Hospital
Camperdown, , Australia
St Vincent's Hospital Sydney
Darlinghurst, , Australia
Austin Health
Heidelberg, , Australia
The Alfred Hospital, Alfred Health
Melbourne, , Australia
Westmead Hospital
Westmead, , Australia
William Osler Health System-Brampton Civic Hospital
Brampton, , Canada
University of Calgary Liver Unit (Heritage Medical Research Clinic)
Calgary, , Canada
Chronic Viral Illness Service McGill University Health Centre (MUHC)/ Royal Victoria Hospital
Montreal, , Canada
Toronto General Hospital
Toronto, , Canada
Toronto Liver Centre
Toronto, , Canada
Prince of Wales Hospital
Shatin, , Hong Kong
Auckland City Hospital
Auckland, , New Zealand
Fundacion de Investigacion de Diego
San Juan, , Puerto Rico
Countries
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References
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Loomba R, et al. Safety and efficacy of combination therapies including cilofexor/firsocostat in patients with bridging fibrosis and cirrhosis due to NASH: Results of the Phase 2b ATLAS trial [accepted for oral presentation]. European Association for the Study of the Liver (EASL); 2020; Virtual.
Loomba R, Alkhouri N, Strasser S, Wong VWS, Schall RA, McColgan B, et al. Clinical utility and application of non-invasive tests of fibrosis in the selection of patients with advanced fibrosis due to NASH in the Phase 2 ATLAS trial (Poster SAT-315). EASL; 2019; Vienna, Austria.
Loomba R, Alkhouri N, Patel K, Zhang J, McColgan BJ, Djedjos S, et al. Validation of Cutoffs for Controlled Attenuation Parameter with MRI-Proton Density Fat Fraction (PDFF) as a Reference Standard in Subjects with Nonalcoholic Steatohepatitis (NASH) Across Multiple Randomized, Controlled Trials (Poster 1727). American Association for the Study of Liver Diseases (AASLD); 2019; Boston, MA, USA.
Loomba R, Alkhouri N, Noureddin M, Zhang J, McColgan BJ, Djedjos S, et al. Validation of the Diagnostic Accuracy of Magnetic Resonance Elastography (MRE) for the Detection of Advanced Fibrosis Due to Nash Across Multiple Phase 2 and 3 Clinical Trials (Poster 1728). AASLD; 2019; Boston, MA, USA.
Alkhouri N, Strasser SI, Wong VWS, Aguilar R, Chuang J, Huss R, et al. Alcohol use is Underreported in Clinical Trials of NASH: Baseline Alcohol Biomarkers from a Phase 2 Clinical Trial (Poster 1765). AASLD; 2019; Boston, MA, USA.
Loomba R, Noureddin M, Kowdley KV, Kohli A, Sheikh A, Neff G, Bhandari BR, Gunn N, Caldwell SH, Goodman Z, Wapinski I, Resnick M, Beck AH, Ding D, Jia C, Chuang JC, Huss RS, Chung C, Subramanian GM, Myers RP, Patel K, Borg BB, Ghalib R, Kabler H, Poulos J, Younes Z, Elkhashab M, Hassanein T, Iyer R, Ruane P, Shiffman ML, Strasser S, Wong VW, Alkhouri N; for the ATLAS Investigators. Combination Therapies Including Cilofexor and Firsocostat for Bridging Fibrosis and Cirrhosis Attributable to NASH. Hepatology. 2021 Feb;73(2):625-643. doi: 10.1002/hep.31622.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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GS-US-454-4378
Identifier Type: -
Identifier Source: org_study_id