AzTrials
AzTrials

Nonalcoholic SteatohepatitisPhase 2ATLASNCT03449446

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)

A Phase 2 study testing SEL, FIR and CILO in people with Nonalcoholic Steatohepatitis, run by Gilead Sciences at 101 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Nonalcoholic Steatohepatitis
What is being tested?
SEL, FIR and CILO
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
395 participants
Where
101 sitesin 6 countries
Study dates
21 Mar 2018to 19 Nov 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

101 sites in 6 countries.

101 sites in 6 countries

United States81 sites

  • Texas Clinical Research Institute, LLC

    Arlington, Texas, 76012

  • Digestive Healthcare of Georgia

    Atlanta, Georgia, 30309

  • Piedmont Hospital

    Atlanta, Georgia, 30309

  • Pinnacle Clinical Research, PLLC

    Austin, Texas, 78746

  • Austin Center for Clinical Research

    Austin, Texas, 78758

  • Mercy Medical Center

    Baltimore, Maryland, 21202

  • Delta Research Partners, LLC

    Bastrop, Louisiana, 71220

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Digestive Disease Associates, PA

    Catonsville, Maryland, 21228

  • The Institute for Liver Health

    Chandler, Arizona, 85224-5688

  • Medical University of South Carolina (Liver Biopsy)

    Charleston, South Carolina, 29425

  • Carolinas Healthcare System Center for Liver Disease and Transplant

    Charlotte, North Carolina, 28204

  • University of Virginia Medical Center

    Charlottesville, Virginia, 22908

  • Northwestern University; Feinberg School of Medicine

    Chicago, Illinois, 60611

  • eStudySite

    Chula Vista, California, 91911-6660

  • Consultants for Clinical Research wed

    Cincinnati, Ohio, 45249

  • Iowa Digestive Disease Center, P.C.

    Clive, Iowa, 50325

  • Gastrointestinal Diseases Research

    Columbus, Georgia, 31904

  • Southern California Liver Center

    Coronado, California, 92118

  • The Liver Institute at Methodist Dallas Medical Center

    Dallas, Texas, 75203

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

    Dallas, Texas, 75390

  • Henry Ford Health Systems

    Detroit, Michigan, 48202

  • Integrity Clinical Research

    Doral, Florida, 33166

  • Duke University Medical Center, Duke South Clinics

    Durham, North Carolina, 27710

  • South Denver Gastroenterology, PC

    Englewood, Colorado, 80113

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

    Falls Church, Virginia, 22042

  • Cumberland Research Associates, LLC

    Fayetteville, North Carolina, 28304

  • Fresno Clinical Research Center

    Fresno, California, 93720

  • UF Hepatology Research at CTRB

    Gainesville, Florida, 32610

  • Gastro One

    Germantown, Tennessee, 38138

  • GHS Gastroenterology and Liver Center

    Greenville, South Carolina, 29605

  • Baylor College of Medicine - Advanced Liver Therapies

    Houston, Texas, 77030

  • Houston Methodist Hospital

    Houston, Texas, 77030

  • Indianapolis Gastroenterology Research Foundation

    Indianapolis, Indiana, 46237

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Saint Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • UCSD NAFLD Clinical Research Center

    La Jolla, California, 92037

  • Jubilee Clinical Research, Inc.

    Las Vegas, Nevada, 89106

  • Liver Wellness Center

    Little Rock, Arkansas, 72204

  • Pinnacle Clinical Research

    Live Oak, Texas, 78233

  • Ruane Clinical Research Group Inc.

    Los Angeles, California, 90036

  • Cedars-Sinai Medical Center

    Los Angeles, California, 99352

  • Sandra Atlas Bass Center for Liver Diseases and Transplantation

    Manhasset, New York, 11030

  • Gastrointestinal Specialists of Georgia

    Marietta, Georgia, 30060

  • Schiff Center for Liver Diseases/University of Miami

    Miami, Florida, 33136

  • IMIC Inc

    Miami, Florida, 33157

  • Genoma Research Group

    Miami, Florida, 33165

  • Intermountain Liver Disease and Transplant Center

    Murray, Utah, 84107

  • Quality Medical Research, PLLC

    Nashville, Tennessee, 37211

  • Tulane University

    New Orleans, Louisiana, 70112

  • Icahn School of Medicine at Mount Sinai Beth Israel

    New York, New York, 10003

  • Concorde Medical Group, PLLC

    New York, New York, 10016

  • NYU Langone Health

    New York, New York, 10016

  • Weill Cornell Medical College

    New York, New York, 10021

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • Rutgers New Jersey Medical School- Doctors Office Center

    Newark, New Jersey, 07103

  • Digestive and Liver Disease Specialists

    Norfolk, Virginia, 23502

  • Arkansas Gastroenterology

    North Little Rock, Arkansas, 72117

  • California Liver Research Institute

    Pasadena, California, 91105

  • Huntington Medical Research Institutes Liver Center

    Pasadena, California, 91105

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

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Mayo Clinic Arizona, Mayo Clinic Hospital

    Phoenix, Arizona, 85054

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

    Pittsburgh, Pennsylvania, 15213

  • VA Pittsburgh Healthcare System

    Pittsburgh, Pennsylvania, 15240

  • University Gastroenterology

    Providence, Rhode Island, 02905

  • Inland Empire Liver Foundation

    Rialto, California, 92377

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

    Richmond, Virginia, 23226

  • McGuire DVAMC

    Richmond, Virginia, 23249

  • Southern Therapy and Advanced Research (STAR) LLC

    Ridgeland, Mississippi, 39157

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California, Davis Medical Center (study visits)

    Sacramento, California, 95817

  • University of Utah Hospital

    Salt Lake City, Utah, 84132

  • American Research Corporation at Texas Liver Institute

    San Antonio, Texas, 78215

  • Medical Associates Research Group

    San Diego, California, 92123

  • Virginia Mason Medical Center

    Seattle, Washington, 98101

  • Swedish Organ Transplant and Liver Center

    Seattle, Washington, 98104

  • Louisiana Research Center, LLC

    Shreveport, Louisiana, 71105

  • Saint Louis University

    St Louis, Missouri, 63110

  • Florida Research Institute

    Tampa, Florida, 34211

  • Montefiore Medical Center

    The Bronx, New York, 10467

Other trials in United States

Australia12 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Royal Prince Alfred Hospital

    Camperdown, 2050

  • Monash Health, Monash Medical Centre

    Clayton, Victoria, 3168

  • St Vincent's Hospital Sydney

    Darlinghurst, 2010

  • St Vincent's Hospital Melbourne

    Fitzroy, Victoria, 3065

  • Austin Health

    Heidelberg, 3084

  • Royal Brisbane & Women's Hospital

    Herston, Queensland, 4029

  • The Alfred Hospital, Alfred Health

    Melbourne, 3004

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

  • Melbourne Health, Royal Melbourne Hospital

    Parkville, Victoria, 3050

  • Royal Perth Hospital

    Perth, Western Australia, 6000

  • Westmead Hospital

    Westmead, 2145

Other trials in Australia

Canada5 sites

  • William Osler Health System-Brampton Civic Hospital

    Brampton, L6R 3J7

  • University of Calgary Liver Unit (Heritage Medical Research Clinic)

    Calgary, T2N 4Z6

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

    Montreal, H4A 3J1

  • Toronto General Hospital

    Toronto, M5G 2C4

  • Toronto Liver Centre

    Toronto, M6H 3M1

Other trials in Canada

Hong Kong1 site

  • Prince of Wales Hospital

    Shatin

Other trials in Hong Kong

New Zealand1 site

  • Auckland City Hospital

    Auckland, 1023

Other trials in New Zealand

Puerto Rico1 site

  • Fundacion de Investigacion de Diego

    San Juan, 00927

Other trials in Puerto Rico

About this study

Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Selonsertib, GS-0976, GS-9674, and Combinations in Subjects With Bridging (F3) Fibrosis or Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)

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
Being tested
SEL, FIR, CILO, Placebo to match FIR, Placebo to match CILO
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SELDrug

    18 mg tablet administered orally once daily without regard to food

  • FIRDrug

    Also called GS-0976

    20 mg tablet administered orally once daily without regard to food

  • CILODrug

    Also called GS-9674

    30 mg tablet administered orally once daily without regard to food

  • Placebo to match FIRDrug

    Tablet administered orally once daily without regard to food

  • Placebo to match CILODrug

    Tablet administered orally once daily without regard to food

  • Placebo to match SELDrug

    Tablet administered orally once daily without regard to food

Study groups in NCT03449446
Study groupRoleWhat they receive
Selonsertib (SEL)ExperimentalParticipants will receive SEL + placebo to match firsocostat 20 mg tablet + placebo to match cilofexor 30 mg tablet orally once daily for 48 weeks.
Receives: Drug: SEL; Drug: Placebo to match FIR; Drug: Placebo to match CILO
Firsocostat (FIR)ExperimentalParticipants will receive placebo to match SEL 18 mg tablet + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
Receives: Drug: FIR; Drug: Placebo to match CILO; Drug: Placebo to match SEL
Cilofexor (CILO)ExperimentalParticipants will receive placebo to match SEL 18 mg tablet + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.
Receives: Drug: CILO; Drug: Placebo to match FIR; Drug: Placebo to match SEL
Selonsertib (SEL) + Firsocostat (FIR)ExperimentalParticipants will receive SEL + FIR + placebo to match CILO 30 mg tablet orally once daily for 48 weeks.
Receives: Drug: SEL; Drug: FIR; Drug: Placebo to match CILO
Selonsertib (SEL) + Cilofexor (CILO)ExperimentalParticipants will receive SEL + placebo to match FIR 20 mg tablet + CILO orally once daily for 48 weeks.
Receives: Drug: SEL; Drug: CILO; Drug: Placebo to match FIR
Firsocostat (FIR) + Cilofexor (CILO)ExperimentalParticipants will receive placebo to match SEL 18 mg tablet + FIR + CILO orally once daily for 48 weeks.
Receives: Drug: FIR; Drug: CILO; Drug: Placebo to match SEL
PlaceboExperimentalParticipants 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.
Receives: Drug: Placebo to match FIR; Drug: Placebo to match CILO; Drug: Placebo to match SEL

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

    Measured: First dose date up to 48 weeks plus 30 days

  2. 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.

    Measured: First dose date up to 48 weeks plus 30 days

  3. 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.

    Measured: Week 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2018
  2. Study start21 Mar 2018
  3. Primary completion30 Oct 2019
  4. Study completion19 Nov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
395 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03449446
Sponsor's protocol ID
GS-US-454-4378
Acronym
ATLAS
Status last verified
Dec 2020
First submitted
23 Feb 2018
Last updated
3 Dec 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33169409

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SEL, FIR and CILO in people with Nonalcoholic Steatohepatitis, run by Gilead Sciences at 101 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 101 sites in United States, Australia, Canada, Hong Kong, New Zealand and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) (time frame: First dose date up to 48 weeks plus 30 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03449446, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in