Nonalcoholic Steatohepatitis Clinical Trial
— ATLASOfficial 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)
| Verified date | December 2020 |
| Source | Gilead Sciences |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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
| Status | Completed |
| Enrollment | 395 |
| Est. completion date | November 19, 2019 |
| Est. primary completion date | October 30, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 80 Years |
| Eligibility | Key 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 Key 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 |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Royal Adelaide Hospital | Adelaide | South Australia |
| Australia | Royal Prince Alfred Hospital | Camperdown | |
| Australia | Monash Health, Monash Medical Centre | Clayton | Victoria |
| Australia | St Vincent's Hospital Sydney | Darlinghurst | |
| Australia | St Vincent's Hospital Melbourne | Fitzroy | Victoria |
| Australia | Austin Health | Heidelberg | |
| Australia | Royal Brisbane & Women's Hospital | Herston | Queensland |
| Australia | The Alfred Hospital, Alfred Health | Melbourne | |
| Australia | Sir Charles Gairdner Hospital | Nedlands | Western Australia |
| Australia | Melbourne Health, Royal Melbourne Hospital | Parkville | Victoria |
| Australia | Royal Perth Hospital | Perth | Western Australia |
| Australia | Westmead Hospital | Westmead | |
| Canada | 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 | |
| Hong Kong | Prince of Wales Hospital | Shatin | |
| New Zealand | Auckland City Hospital | Auckland | |
| Puerto Rico | Fundacion de Investigacion de Diego | San Juan | |
| United States | Texas Clinical Research Institute, LLC | Arlington | Texas |
| United States | Digestive Healthcare of Georgia | Atlanta | Georgia |
| United States | Piedmont Hospital | Atlanta | Georgia |
| United States | Austin Center for Clinical Research | Austin | Texas |
| United States | Pinnacle Clinical Research, PLLC | Austin | Texas |
| United States | Mercy Medical Center | Baltimore | Maryland |
| United States | Delta Research Partners, LLC | Bastrop | Louisiana |
| United States | Beth Israel Deaconess Medical Center | Boston | Massachusetts |
| United States | Montefiore Medical Center | Bronx | New York |
| United States | Digestive Disease Associates, PA | Catonsville | Maryland |
| United States | The Institute for Liver Health | Chandler | Arizona |
| United States | Medical University of South Carolina (Liver Biopsy) | Charleston | South Carolina |
| United States | Carolinas Healthcare System Center for Liver Disease and Transplant | Charlotte | North Carolina |
| United States | University of Virginia Medical Center | Charlottesville | Virginia |
| United States | Northwestern University; Feinberg School of Medicine | Chicago | Illinois |
| United States | eStudySite | Chula Vista | California |
| United States | Consultants for Clinical Research wed | Cincinnati | Ohio |
| United States | Iowa Digestive Disease Center, P.C. | Clive | Iowa |
| United States | Gastrointestinal Diseases Research | Columbus | Georgia |
| United States | Southern California Liver Center | Coronado | California |
| 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 | Henry Ford Health Systems | Detroit | Michigan |
| United States | Integrity Clinical Research | Doral | Florida |
| United States | Duke University Medical Center, Duke South Clinics | Durham | North Carolina |
| United States | South Denver Gastroenterology, PC | Englewood | Colorado |
| United States | California Pacific Medical Center - Sutter Pacific Medical Foundation San Francisco Center for Liver Disease Dept. of Transplant | Falls Church | Virginia |
| United States | Cumberland Research Associates, LLC | Fayetteville | North Carolina |
| United States | Fresno Clinical Research Center | Fresno | California |
| United States | UF Hepatology Research at CTRB | Gainesville | Florida |
| United States | Gastro One | Germantown | Tennessee |
| United States | GHS Gastroenterology and Liver Center | Greenville | South Carolina |
| United States | Baylor College of Medicine - Advanced Liver Therapies | Houston | Texas |
| United States | Houston Methodist Hospital | Houston | Texas |
| United States | Indianapolis Gastroenterology Research Foundation | Indianapolis | Indiana |
| United States | Saint Luke's Hospital of Kansas City | Kansas City | Missouri |
| United States | University of Kansas Medical Center | Kansas City | Kansas |
| United States | UCSD NAFLD Clinical Research Center | La Jolla | California |
| United States | Jubilee Clinical Research, Inc. | Las Vegas | Nevada |
| United States | Liver Wellness Center | Little Rock | Arkansas |
| United States | Pinnacle Clinical Research | Live Oak | Texas |
| United States | Cedars-Sinai Medical Center | Los Angeles | California |
| United States | Ruane Clinical Research Group Inc. | Los Angeles | California |
| United States | Sandra Atlas Bass Center for Liver Diseases and Transplantation | Manhasset | New York |
| United States | Gastrointestinal Specialists of Georgia | Marietta | Georgia |
| United States | Genoma Research Group | Miami | Florida |
| United States | IMIC Inc | Miami | Florida |
| United States | Schiff Center for Liver Diseases/University of Miami | Miami | Florida |
| United States | Intermountain Liver Disease and Transplant Center | Murray | Utah |
| United States | Quality Medical Research, PLLC | Nashville | Tennessee |
| United States | Tulane University | New Orleans | Louisiana |
| United States | Concorde Medical Group, PLLC | New York | New York |
| United States | Icahn School of Medicine at Mount Sinai | New York | New York |
| United States | Icahn School of Medicine at Mount Sinai Beth Israel | 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 | Rutgers New Jersey Medical School- Doctors Office Center | Newark | New Jersey |
| United States | Digestive and Liver Disease Specialists | Norfolk | Virginia |
| United States | Arkansas Gastroenterology | North Little Rock | Arkansas |
| United States | California Liver Research Institute | Pasadena | California |
| United States | Huntington Medical Research Institutes Liver Center | Pasadena | California |
| United States | Hospital of the University of Pennsylvania- Perelman Center for Advanced Medicine | Philadelphia | Pennsylvania |
| United States | Thomas Jefferson University | Philadelphia | Pennsylvania |
| United States | Mayo Clinic Arizona, Mayo Clinic Hospital | Phoenix | Arizona |
| 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 | Inland Empire Liver Foundation | Rialto | California |
| 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 | Southern Therapy and Advanced Research (STAR) LLC | Ridgeland | Mississippi |
| United States | Mayo Clinic | Rochester | Minnesota |
| United States | University of California, Davis Medical Center (study visits) | Sacramento | California |
| United States | Saint Louis University | Saint Louis | Missouri |
| United States | University of Utah Hospital | Salt Lake City | Utah |
| United States | American Research Corporation at Texas Liver Institute | San Antonio | Texas |
| United States | Medical Associates Research Group | San Diego | California |
| United States | Swedish Organ Transplant and Liver Center | Seattle | Washington |
| United States | Virginia Mason Medical Center | Seattle | Washington |
| United States | Louisiana Research Center, LLC | Shreveport | Louisiana |
| United States | Florida Research Institute | Tampa | Florida |
| Lead Sponsor | Collaborator |
|---|---|
| Gilead Sciences |
United States, Australia, Canada, Hong Kong, New Zealand, Puerto Rico,
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, 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 (Pos
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) Acro
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;
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
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | First dose date up to 48 weeks plus 30 days | ||
| Primary | 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 | |
| Primary | 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 |
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