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, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Selonsertib, Firsocostat, Cilofexor, and Combinations in Subjects With Bridging (F3) Fibrosis or Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)

Sponsoren

Hauptsponsor: Gilead Sciences

Quelle Gilead Sciences
Kurze Zusammenfassung

The primary objectives of this study are:

- To assess the safety and tolerability of selonsertib (SEL), firsocostat, and cilofexor, administered alone or in combination, in participants with bridging fibrosis or compensated cirrhosis due to Nonalcoholic Steatohepatitis (NASH)

- To evaluate changes in liver fibrosis, without worsening of NASH

Gesamtstatus Completed
Anfangsdatum March 21, 2018
Fertigstellungstermin November 19, 2019
Primäres Abschlussdatum November 19, 2019
Phase Phase 2
Studientyp Interventional
Primärer Ausgang
Messen Zeitfenster
Proportion of Participants Experiencing Adverse Events Up to 52 Weeks
Proportion of Participants Experiencing Laboratory Abnormalities Up to 52 weeks
Proportion of Participants who Achieve a ≥ 1-Stage Improvement in fibrosis without worsening of NASH at Week 48 Week 48
Einschreibung 395
Bedingung
Intervention

Interventionsart: Drug

Interventionsname: SEL

Beschreibung: 18 mg tablet administered orally once daily without regard to food

Interventionsart: Drug

Interventionsname: Firsocostat

Beschreibung: 20 mg tablet administered orally once daily without regard to food

Anderer Name: GS-0976

Interventionsart: Drug

Interventionsname: Cilofexor

Beschreibung: 30 mg tablet administered orally once daily without regard to food

Anderer Name: GS-9674

Interventionsart: Drug

Interventionsname: SEL Placebo

Beschreibung: Tablet administered orally once daily without regard to food

Interventionsart: Drug

Interventionsname: Firsocostat Placebo

Beschreibung: Tablet administered orally once daily without regard to food

Interventionsart: Drug

Interventionsname: Cilofexor Placebo

Beschreibung: Tablet administered orally once daily without regard to food

Teilnahmeberechtigung

Kriterien:

Key Inclusion Criteria:

- Liver biopsy consistent with NASH and bridging fibrosis (F3) and cirrhosis (F4) in the opinion of the central reader

- In participants who have never had a liver biopsy, liver stiffness by FibroScan® and Enhanced Liver Fibrosis (ELF™) Test score 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

- 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

Geschlecht: All

Mindestalter: 18 Years

Maximales Alter: 80 Years

Gesunde Freiwillige: No

Insgesamt offiziell
Nachname Rolle Zugehörigkeit
Gilead Study Director Study Director Gilead Sciences
Ort
Einrichtung:
The Institute for Liver Health | Chandler, Arizona, 85224-5688, United States
Mayo Clinic Arizona, Mayo Clinic Hospital | Phoenix, Arizona, 85054, United States
Liver Wellness Center | Little Rock, Arkansas, 72204, United States
Arkansas Gastroenterology | North Little Rock, Arkansas, 72117, United States
eStudySite | Chula Vista, California, 91911-6660, United States
Southern California Liver Center | Coronado, California, 92118, United States
Fresno Clinical Research Center | Fresno, California, 93720, United States
UCSD NAFLD Clinical Research Center | La Jolla, California, 92037, United States
Ruane Clinical Research Group Inc. | Los Angeles, California, 90036, United States
Cedars-Sinai Medical Center | Los Angeles, California, 99352, United States
California Liver Research Institute | Pasadena, California, 91105, United States
Huntington Medical Research Institutes Liver Center | Pasadena, California, 91105, United States
Inland Empire Liver Foundation | Rialto, California, 92377, United States
University of California, Davis Medical Center (study visits) | Sacramento, California, 95817, United States
Medical Associates Research Group | San Diego, California, 92123, United States
South Denver Gastroenterology, PC | Englewood, Colorado, 80113, United States
Integrity Clinical Research | Doral, Florida, 33166, United States
UF Hepatology Research at CTRB | Gainesville, Florida, 32610, United States
Schiff Center for Liver Diseases/University of Miami | Miami, Florida, 33136, United States
IMIC Inc | Miami, Florida, 33157, United States
Genoma Research Group | Miami, Florida, 33165, United States
Florida Research Institute | Tampa, Florida, 34211, United States
Digestive Healthcare of Georgia | Atlanta, Georgia, 30309, United States
Piedmont Hospital | Atlanta, Georgia, 30309, United States
Gastrointestinal Diseases Research | Columbus, Georgia, 31904, United States
Gastrointestinal Specialists of Georgia | Marietta, Georgia, 30060, United States
Northwestern University; Feinberg School of Medicine | Chicago, Illinois, 60611, United States
Indianapolis Gastroenterology Research Foundation | Indianapolis, Indiana, 46237, United States
Iowa Digestive Disease Center, P.C. | Clive, Iowa, 50325, United States
University of Kansas Medical Center | Kansas City, Kansas, 66160, United States
Delta Research Partners, LLC | Bastrop, Louisiana, 71220, United States
Tulane University | New Orleans, Louisiana, 70112, United States
Louisiana Research Center, LLC | Shreveport, Louisiana, 71105, United States
Mercy Medical Center | Baltimore, Maryland, 21202, United States
Digestive Disease Associates, PA | Catonsville, Maryland, 21228, United States
Beth Israel Deaconess Medical Center | Boston, Massachusetts, 02215, United States
Henry Ford Health Systems | Detroit, Michigan, 48202, United States
Mayo Clinic | Rochester, Minnesota, 55905, United States
Southern Therapy and Advanced Research (STAR) LLC | Ridgeland, Mississippi, 39157, United States
Saint Luke's Hospital of Kansas City | Kansas City, Missouri, 64111, United States
Saint Louis University | Saint Louis, Missouri, 63110, United States
Jubilee Clinical Research, Inc. | Las Vegas, Nevada, 89106, United States
Rutgers New Jersey Medical School- Doctors Office Center | Newark, New Jersey, 07103, United States
Montefiore Medical Center | Bronx, New York, 10467, United States
Sandra Atlas Bass Center for Liver Diseases and Transplantation | Manhasset, New York, 11030, United States
Icahn School of Medicine at Mount Sinai Beth Israel | New York, New York, 10003, United States
Concorde Medical Group, PLLC | New York, New York, 10016, United States
NYU Langone Health | New York, New York, 10016, United States
Weill Cornell Medical College | New York, New York, 10021, United States
Icahn School of Medicine at Mount Sinai | New York, New York, 10029, United States
Carolinas Healthcare System Center for Liver Disease and Transplant | Charlotte, North Carolina, 28204, United States
Duke University Medical Center, Duke South Clinics | Durham, North Carolina, 27710, United States
Cumberland Research Associates, LLC | Fayetteville, North Carolina, 28304, United States
Consultants for Clinical Research wed | Cincinnati, Ohio, 45249, United States
Hospital of the University of Pennsylvania- Perelman Center for Advanced Medicine | Philadelphia, Pennsylvania, 19104, United States
Thomas Jefferson University | Philadelphia, Pennsylvania, 19107, United States
UPMC - Center for Liver Diseases at the Thomas E. Starlz Institute | Pittsburgh, Pennsylvania, 15213, United States
VA Pittsburgh Healthcare System | Pittsburgh, Pennsylvania, 15240, United States
University Gastroenterology | Providence, Rhode Island, 02905, United States
Medical University of South Carolina (Liver Biopsy) | Charleston, South Carolina, 29425, United States
GHS Gastroenterology and Liver Center | Greenville, South Carolina, 29605, United States
Gastro One | Germantown, Tennessee, 38138, United States
Quality Medical Research, PLLC | Nashville, Tennessee, 37211, United States
Texas Clinical Research Institute, LLC | Arlington, Texas, 76012, United States
Pinnacle Clinical Research, PLLC | Austin, Texas, 78746, United States
Austin Center for Clinical Research | Austin, Texas, 78758, United States
The Liver Institute at Methodist Dallas Medical Center | Dallas, Texas, 75203, United States
University of Texas Southwestern Medical Center Internal Medicine Digestive and Liver Diseases Clinical Trials | Dallas, Texas, 75390, United States
Baylor College of Medicine - Advanced Liver Therapies | Houston, Texas, 77030, United States
Houston Methodist Hospital | Houston, Texas, 77030, United States
Pinnacle Clinical Research | Live Oak, Texas, 78233, United States
American Research Corporation at Texas Liver Institute | San Antonio, Texas, 78215, United States
Intermountain Liver Disease and Transplant Center | Murray, Utah, 84107, United States
University of Utah Hospital | Salt Lake City, Utah, 84132, United States
University of Virginia Medical Center | Charlottesville, Virginia, 22908, United States
California Pacific Medical Center - Sutter Pacific Medical Foundation San Francisco Center for Liver Disease Dept. of Transplant | Falls Church, Virginia, 22042, United States
Digestive and Liver Disease Specialists | Norfolk, Virginia, 23502, United States
Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond | Richmond, Virginia, 23226, United States
McGuire DVAMC | Richmond, Virginia, 23249, United States
Virginia Mason Medical Center | Seattle, Washington, 98101, United States
Swedish Organ Transplant and Liver Center | Seattle, Washington, 98104, United States
Royal Brisbane & Women's Hospital | Herston, Queensland, 4029, Australia
Royal Adelaide Hospital | Adelaide, South Australia, 5000, Australia
Monash Health, Monash Medical Centre | Clayton, Victoria, 3168, Australia
St Vincent's Hospital Melbourne | Fitzroy, Victoria, 3065, Australia
Melbourne Health, Royal Melbourne Hospital | Parkville, Victoria, 3050, Australia
Sir Charles Gairdner Hospital | Nedlands, Western Australia, 6009, Australia
Royal Perth Hospital | Perth, Western Australia, 6000, Australia
Royal Prince Alfred Hospital | Camperdown, 2050, Australia
St Vincent's Hospital Sydney | Darlinghurst, 2010, Australia
Austin Health | Heidelberg, 3084, Australia
The Alfred Hospital, Alfred Health | Melbourne, 3004, Australia
Westmead Hospital | Westmead, 2145, Australia
William Osler Health System-Brampton Civic Hospital | Brampton, L6R 3J7, Canada
University of Calgary Liver Unit (Heritage Medical Research Clinic) | Calgary, T2N 4Z6, Canada
Chronic Viral Illness Service McGill University Health Centre (MUHC)/ Royal Victoria Hospital | Montreal, H4A 3J1, Canada
Toronto General Hospital | Toronto, M5G 2C4, Canada
Toronto Liver Centre | Toronto, M6H 3M1, Canada
Prince of Wales Hospital | Shatin, Hong Kong
Auckland City Hospital | Auckland, 1023, New Zealand
Fundacion de Investigacion de Diego | San Juan, 00927, Puerto Rico
Standort Länder

Australia

Canada

Hong Kong

New Zealand

Puerto Rico

United States

Überprüfungsdatum

December 2019

Verantwortliche Partei

Art: Sponsor

Hat den Zugriff erweitert No
Bedingung Durchsuchen
Anzahl der Waffen 7
Armgruppe

Etikette: SEL+ Firsocostat + Cilofexor Placebo

Art: Experimental

Beschreibung: SEL + Firsocostat + Cilofexor Placebo for 48 weeks

Etikette: SEL+ Firsocostat Placebo + Cilofexor

Art: Experimental

Beschreibung: SEL + Firsocostat Placebo + Cilofexor for 48 weeks

Etikette: SEL+ Firsocostat Placebo + Cilofexor Placebo

Art: Experimental

Beschreibung: SEL + Firsocostat Placebo + Cilofexor Placebo for 48 weeks

Etikette: SEL Placebo + Firsocostat + Cilofexor Placebo

Art: Experimental

Beschreibung: SEL Placebo + Firsocostat + Cilofexor Placebo for 48 weeks

Etikette: SEL Placebo + Firsocostat Placebo + Cilofexor

Art: Experimental

Beschreibung: SEL Placebo + Firsocostat Placebo + Cilofexor for 48 weeks

Etikette: SEL Placebo + Firsocostat Placebo + Cilofexor Placebo

Art: Experimental

Beschreibung: SEL Placebo + Firsocostat Placebo + Cilofexor Placebo for 48 weeks

Etikette: SEL Placebo + Firsocostat + Cilofexor

Art: Experimental

Beschreibung: SEL Placebo + Firsocostat + Cilofexor for 48 weeks

Akronym ATLAS
Patientendaten No
Studiendesign Info

Zuweisung: Randomized

Interventionsmodell: Parallel Assignment

Hauptzweck: Treatment

Maskierung: Double (Participant, Investigator)

Quelle: ClinicalTrials.gov