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)

NCT03449446 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: GS-US-454-4378
• Study Type: interventional
• Target: 395
• Locations: 6 countries
• Sites: 101

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

Conditions

Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (3)

• 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

  Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. Participants with any laboratory abnormality were reported.

  First dose date up to 48 weeks plus 30 days

• Percentage of Participants Who Achieved a ≥ 1-Stage Improvement in Fibrosis Without Worsening of NASH at 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.

  Week 48

Study Arms (7)

Selonsertib (SEL)

EXPERIMENTAL

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; Drug: Placebo to match FIR; Drug: Placebo to match CILO

Firsocostat (FIR)

EXPERIMENTAL

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; Drug: Placebo to match CILO; Drug: Placebo to match SEL

Cilofexor (CILO)

EXPERIMENTAL

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; Drug: Placebo to match FIR; Drug: Placebo to match SEL

Selonsertib (SEL) + Firsocostat (FIR)

EXPERIMENTAL

Participants will receive SEL + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.

Drug: SEL; Drug: FIR; Drug: Placebo to match CILO

Selonsertib (SEL) + Cilofexor (CILO)

EXPERIMENTAL

Participants will receive SEL + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.

Drug: SEL; Drug: CILO; Drug: Placebo to match FIR

Firsocostat (FIR) + Cilofexor (CILO)

EXPERIMENTAL

Participants will receive placebo to match SEL 18 mg tablet + FIR + CILO orally once daily for 48 weeks.

Drug: FIR; Drug: CILO; Drug: Placebo to match SEL

Placebo

EXPERIMENTAL

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; Drug: Placebo to match CILO; Drug: Placebo to match SEL

Interventions

SEL DRUG

18 mg tablet administered orally once daily without regard to food

Selonsertib (SEL); Selonsertib (SEL) + Cilofexor (CILO); Selonsertib (SEL) + Firsocostat (FIR)

FIR DRUG

20 mg tablet administered orally once daily without regard to food

Also known as: GS-0976

Firsocostat (FIR); Firsocostat (FIR) + Cilofexor (CILO); Selonsertib (SEL) + Firsocostat (FIR)

CILO DRUG

30 mg tablet administered orally once daily without regard to food

Also known as: GS-9674

Cilofexor (CILO); Firsocostat (FIR) + Cilofexor (CILO); Selonsertib (SEL) + Cilofexor (CILO)

Placebo to match FIR DRUG

Tablet administered orally once daily without regard to food

Cilofexor (CILO); Placebo; Selonsertib (SEL); Selonsertib (SEL) + Cilofexor (CILO)

Placebo to match CILO DRUG

Tablet administered orally once daily without regard to food

Firsocostat (FIR); Placebo; Selonsertib (SEL); Selonsertib (SEL) + Firsocostat (FIR)

Placebo to match SEL DRUG

Tablet administered orally once daily without regard to food

Cilofexor (CILO); Firsocostat (FIR); Firsocostat (FIR) + Cilofexor (CILO); Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (101)

The Institute for Liver Health

Chandler, Arizona, 85224-5688, United States

Location

Mayo Clinic Arizona, Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Liver Wellness Center

Little Rock, Arkansas, 72204, United States

Location

Arkansas Gastroenterology

North Little Rock, Arkansas, 72117, United States

Location

eStudySite

Chula Vista, California, 91911-6660, United States

Location

Southern California Liver Center

Coronado, California, 92118, United States

Location

Fresno Clinical Research Center

Fresno, California, 93720, United States

Location

UCSD NAFLD Clinical Research Center

La Jolla, California, 92037, United States

Location

Ruane Clinical Research Group Inc.

Los Angeles, California, 90036, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 99352, United States

Location

California Liver Research Institute

Pasadena, California, 91105, United States

Location

Huntington Medical Research Institutes Liver Center

Pasadena, California, 91105, United States

Location

Inland Empire Liver Foundation

Rialto, California, 92377, United States

Location

University of California, Davis Medical Center (study visits)

Sacramento, California, 95817, United States

Location

Medical Associates Research Group

San Diego, California, 92123, United States

Location

South Denver Gastroenterology, PC

Englewood, Colorado, 80113, United States

Location

Integrity Clinical Research

Doral, Florida, 33166, United States

Location

UF Hepatology Research at CTRB

Gainesville, Florida, 32610, United States

Location

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, 33136, United States

Location

IMIC Inc

Miami, Florida, 33157, United States

Location

Genoma Research Group

Miami, Florida, 33165, United States

Location

Florida Research Institute

Tampa, Florida, 34211, United States

Location

Digestive Healthcare of Georgia

Atlanta, Georgia, 30309, United States

Location

Piedmont Hospital

Atlanta, Georgia, 30309, United States

Location

Gastrointestinal Diseases Research

Columbus, Georgia, 31904, United States

Location

Gastrointestinal Specialists of Georgia

Marietta, Georgia, 30060, United States

Location

Northwestern University; Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Indianapolis Gastroenterology Research Foundation

Indianapolis, Indiana, 46237, United States

Location

Iowa Digestive Disease Center, P.C.

Clive, Iowa, 50325, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Delta Research Partners, LLC

Bastrop, Louisiana, 71220, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Louisiana Research Center, LLC

Shreveport, Louisiana, 71105, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Digestive Disease Associates, PA

Catonsville, Maryland, 21228, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health Systems

Detroit, Michigan, 48202, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Southern Therapy and Advanced Research (STAR) LLC

Ridgeland, Mississippi, 39157, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Saint Louis University

St Louis, Missouri, 63110, United States

Location

Jubilee Clinical Research, Inc.

Las Vegas, Nevada, 89106, United States

Location

Rutgers New Jersey Medical School- Doctors Office Center

Newark, New Jersey, 07103, United States

Location

Sandra Atlas Bass Center for Liver Diseases and Transplantation

Manhasset, New York, 11030, United States

Location

Icahn School of Medicine at Mount Sinai Beth Israel

New York, New York, 10003, United States

Location

Concorde Medical Group, PLLC

New York, New York, 10016, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Carolinas Healthcare System Center for Liver Disease and Transplant

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center, Duke South Clinics

Durham, North Carolina, 27710, United States

Location

Cumberland Research Associates, LLC

Fayetteville, North Carolina, 28304, United States

Location

Consultants for Clinical Research wed

Cincinnati, Ohio, 45249, United States

Location

Hospital of the University of Pennsylvania- Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC - Center for Liver Diseases at the Thomas E. Starlz Institute

Pittsburgh, Pennsylvania, 15213, United States

Location

VA Pittsburgh Healthcare System

Pittsburgh, Pennsylvania, 15240, United States

Location

University Gastroenterology

Providence, Rhode Island, 02905, United States

Location

Medical University of South Carolina (Liver Biopsy)

Charleston, South Carolina, 29425, United States

Location

GHS Gastroenterology and Liver Center

Greenville, South Carolina, 29605, United States

Location

Gastro One

Germantown, Tennessee, 38138, United States

Location

Quality Medical Research, PLLC

Nashville, Tennessee, 37211, United States

Location

Texas Clinical Research Institute, LLC

Arlington, Texas, 76012, United States

Location

Pinnacle Clinical Research, PLLC

Austin, Texas, 78746, United States

Location

Austin Center for Clinical Research

Austin, Texas, 78758, United States

Location

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

University of Texas Southwestern Medical Center Internal Medicine Digestive and Liver Diseases Clinical Trials

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine - Advanced Liver Therapies

Houston, Texas, 77030, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Pinnacle Clinical Research

Live Oak, Texas, 78233, United States

Location

American Research Corporation at Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Intermountain Liver Disease and Transplant Center

Murray, Utah, 84107, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

University of Virginia Medical Center

Charlottesville, Virginia, 22908, United States

Location

California Pacific Medical Center - Sutter Pacific Medical Foundation San Francisco Center for Liver Disease Dept. of Transplant

Falls Church, Virginia, 22042, United States

Location

Digestive and Liver Disease Specialists

Norfolk, Virginia, 23502, United States

Location

Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond

Richmond, Virginia, 23226, United States

Location

McGuire DVAMC

Richmond, Virginia, 23249, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Swedish Organ Transplant and Liver Center

Seattle, Washington, 98104, United States

Location

Royal Brisbane & Women's Hospital

Herston, Queensland, 4029, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Monash Health, Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Melbourne Health, Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Royal Prince Alfred Hospital

Camperdown, 2050, Australia

Location

St Vincent's Hospital Sydney

Darlinghurst, 2010, Australia

Location

Austin Health

Heidelberg, 3084, Australia

Location

The Alfred Hospital, Alfred Health

Melbourne, 3004, Australia

Location

Westmead Hospital

Westmead, 2145, Australia

Location

William Osler Health System-Brampton Civic Hospital

Brampton, L6R 3J7, Canada

Location

University of Calgary Liver Unit (Heritage Medical Research Clinic)

Calgary, T2N 4Z6, Canada

Location

Chronic Viral Illness Service McGill University Health Centre (MUHC)/ Royal Victoria Hospital

Montreal, H4A 3J1, Canada

Location

Toronto General Hospital

Toronto, M5G 2C4, Canada

Location

Toronto Liver Centre

Toronto, M6H 3M1, Canada

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Fundacion de Investigacion de Diego

San Juan, 00927, Puerto Rico

Location

Related Publications (6)

• 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.

  RESULT

• 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.

  RESULT

• 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.

  RESULT

• 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.

  RESULT

• 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.

  RESULT

• 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.

  PMID: 33169409 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

firsocostat

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2018
• First Posted: February 28, 2018
• Study Start: March 21, 2018
• Primary Completion: October 30, 2019
• Study Completion: November 19, 2019
• Last Updated: December 3, 2020
• Results First Posted: December 3, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1); US (81); PR (1); AU (12); CA (5); NZ (1)