Clinical trial NCT03439254: Study Evaluating the Efficacy and Safety of Obeticholic Acid in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis
Official title: A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Obeticholic Acid in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Compensated Cirrhosis
Nonalcoholic Steatohepatitis
Keywords: Compensated Cirrhosis
Nonalcoholic Steatohepatitis
Fatty Liver Disease
NASH
Lead sponsor: Intercept Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-02-20
Enrollment: 919
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate whether obeticholic acid (OCA; INT-747) can lead to histological improvement in fibrosis with no worsening of NASH in adults with compensated cirrhosis due to NASH.


Eligibility criteria: Key inclusion criteria:

1. Subjects with a confirmed diagnosis of NASH and a fibrosis score of 4 based upon the NASH CRN scoring system determined by central reading

Key exclusion criteria:

1. Current or past history of a clinically evident hepatic decompensation event, such as ascites, hepatic encephalopathy (HE), or variceal bleeding
2. Current or past history of CP score ≥7 points
3. Model for End-stage Liver Disease (MELD) score \> 12
4. ALT ≥ 5 X ULN
5. Calculated creatinine clearance \<60mL/min using Cockcroft-Gault method
6. Hemoglobin A1c (HbA1c) ≥ 9.5 %
7. Evidence of other known forms of chronic liver disease such as alcoholic liver disease, hepatitis B, hepatitis C, PBC, PSC, autoimmune hepatitis, Wilson disease, iron overload, alpha-1-antitrypsin deficiency, drug-induced liver injury, known or suspected hepatocellular carcinoma (HCC)
8. History of liver transplant, or current placement on a liver transplant list

Primary outcomes:
measure: DB Phase: Number of Participants Who Were Responders and Showed Improvement in Fibrosis by at Least 1 Stage Without Worsening of Nonalcoholic Steatohepatitis (NASH)
timeFrame: Up to 18 months
measure: OLE Phase: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 12 months
measure: OLE Phase: Change From Baseline to Month 12 in Liver Stiffness Measurement (LSM)
timeFrame: Baseline and up to Month 12
measure: OLE Phase: Fibrosis-4 (FIB-4) at Baseline
timeFrame: Baseline (Day 1)
measure: OLE Phase: Enhanced Liver Fibrosis (ELF) at Baseline
timeFrame: Baseline (Day 1)
measure: OLE Phase: Number of Participants Reporting All-cause Mortality
timeFrame: Up to Month 12
measure: OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Ascites, Hepatocellular Carcinoma (HCC) and Non-liver Related Death
timeFrame: Up to 12 months
measure: OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Worsening of Child-Pugh Score
timeFrame: Up to 12 months
measure: OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Model for End-Stage Liver Disease (MELD) Score ≥15
timeFrame: Up to 12 months
Secondary outcomes:
measure: DB Phase: Change From Baseline to Month 18 in LSM
timeFrame: Baseline and up to Month 18
measure: DB Phase: FIB-4 at Baseline
timeFrame: Baseline (Day 1)
measure: DB Phase: ELF at Baseline
timeFrame: Baseline (Day 1)
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Digestive Health Specialists of the Southeast
state: Alabama
city: Madison
country: United States
facility: Objective GI d/b/a North Alabama GI Research Center
state: Alabama
city: Chandler
country: United States
facility: Arizona Liver Health
state: Arizona
city: Glendale
country: United States
facility: Arizona Liver Health
state: Arizona
city: Tucson
country: United States
facility: The Institute for Liver Health
state: Arizona
city: Little Rock
country: United States
facility: Liver Wellness Center
state: Arkansas
city: North Little Rock
country: United States
facility: Arkansas Gastroenterology
state: Arkansas
city: Canoga Park
country: United States
facility: Hope Clinical Research
state: California
city: Fresno
country: United States
facility: University of California, San Francisco-Fresno
state: California
city: La Jolla
country: United States
facility: Scripps Whittier Diabetes Institute
state: California
city: La Mesa
country: United States
facility: eStudySite
state: California
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinani Medical Center
state: California
city: Palm Springs
country: United States
facility: Palmtree Clinical Research, INC.
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Pasadena
country: United States
facility: California Liver Research Institute
state: California
city: Rialto
country: United States
facility: Inland Empire Liver Foundation
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Sacramento Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado Denver and Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Peak Gastroenterology Associates
state: Colorado
city: Englewood
country: United States
facility: South Denver Gastroenterology, PC
state: Colorado
city: Aventura
country: United States
facility: Innovative Medical Research of South Florida, Inc.
state: Florida
city: Coral Gables
country: United States
facility: Hi Tech and Global Research LLC
state: Florida
city: Inverness
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: UF Health Jacksonville-Gastroenterology Emerson
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Miami
country: United States
facility: Schiff Center for Liver Diseases/University of Miami
state: Florida
city: Ocoee
country: United States
facility: Sensible Healthcare, LLC
state: Florida
city: Palmetto Bay
country: United States
facility: Innovation Medical Research Center
state: Florida
city: Pensacola
country: United States
facility: Gastroenterology Associates of Pensacola, PA
state: Florida
city: Tampa
country: United States
facility: Tampa General Medical Group
state: Florida
city: Tampa
country: United States
facility: Guardian Angel Research Center, INC
state: Florida
city: Zephyrhills
country: United States
facility: Florida Medical Clinic, P.A
state: Florida
city: Athens
country: United States
facility: Summit Clinical Research, LLC
state: Georgia
city: Atlanta
country: United States
facility: The Emory Clinic (TEC)
state: Georgia
city: Marietta
country: United States
facility: Gastrointestinal Specialists of Georgia
state: Georgia
city: Idaho Falls
country: United States
facility: Grand Teton Research Group, PLLC
state: Idaho
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: New Albany
country: United States
facility: Aquiant Research
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Topeka
country: United States
facility: Kansas Medical Clinic
state: Kansas
city: Louisville
country: United States
facility: University of Louisville, Clinical Trials Unit
state: Kentucky
city: Marrero
country: United States
facility: Tandem Clinical Research, LLC
state: Louisiana
city: Monroe
country: United States
facility: Delta Research Partners, LLC
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana Research Center
state: Louisiana
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Hospital & Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Health Care
state: Massachusetts
city: Wyoming
country: United States
facility: Gastroenterology Associates of Western Michigan, PLC d.b.a. West Michigan Clinical Research Center
state: Michigan
city: Ypsilanti
country: United States
facility: Huron Gastroenterology Associates
state: Michigan
city: Saint Paul
country: United States
facility: Minnesota Gastroenterology, P.A.
state: Minnesota
city: Jackson
country: United States
facility: Southern Therapy and Advanced Research (STAR) LLC
state: Mississippi
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: CHI Health Alegent Creighton Clinic
state: Nebraska
city: Las Vegas
country: United States
facility: Sierra Clinical Research
state: Nevada
city: Martinsville
country: United States
facility: Amici GI-LLC
state: New Jersey
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: University at Buffalo, Clinical and Translational Research Center
state: New York
city: New York
country: United States
facility: Ichan School of Medicine at Mount Sinai Beth Israel
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Asheville
country: United States
facility: Asheville Gastroenterology Associates, P.A.
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill, School of Medicine
state: North Carolina
city: Charlotte
country: United States
facility: Charlotte Gastroenterology & Hepatology, PLLC
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Huntersville
country: United States
facility: Carolinas Center for Liver Disease/Carolinas HealthCare System
state: North Carolina
city: Huntersville
country: United States
facility: Carolinas Health Care System Center for Liver Disease
state: North Carolina
city: Morehead City
country: United States
facility: Diabetes & Endocrinology Consultants, PC
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates, LLC
state: North Carolina
city: Beavercreek
country: United States
facility: Dayton Gastroenterology, Inc.
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center, LLC
state: Pennsylvania
city: Hershey
country: United States
facility: The Pennsylvania State University and the Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Einstein Healthcare Network
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC - Center for Liver Diseases at the Thomas E. Starzl Institute
state: Pennsylvania
city: Providence
country: United States
facility: University Gastroenterology
state: Rhode Island
city: Charleston
country: United States
facility: Ralph H. Johnson Veterans Affairs Medical Center
state: South Carolina
city: Charleston
country: United States
facility: SCTR Research Nexus
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Medical Center LLP
state: South Dakota
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Hermitage
country: United States
facility: Associates in Gastroenterology, PLC
state: Tennessee
city: Johnson City
country: United States
facility: Johnson City Medical Center
state: Tennessee
city: Memphis
country: United States
facility: Methodist Healthcare University Hospital
state: Tennessee
city: Nashville
country: United States
facility: Quaility Medical Research, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center - Digestive Disease Center
state: Tennessee
city: Arlington
country: United States
facility: Texas Clinical Research Institute LLC
state: Texas
city: Dallas
country: United States
facility: The Liver Institute at Methodist Dallas Medical Center
state: Texas
city: Dallas
country: United States
facility: Liver Center of Texas
state: Texas
city: Dallas
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Fort Sam Houston
country: United States
facility: San Antonio Military Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Baylor Scott and White All Saints Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine - Advanced Liver Therapies
state: Texas
city: Houston
country: United States
facility: The University of Texas Medical School at Houston
state: Texas
city: McAllen
country: United States
facility: Centex Studies, Inc.
state: Texas
city: San Antonio
country: United States
facility: American Research Corporation
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas, Inc.
state: Texas
city: San Marcos
country: United States
facility: Texas Digestive Disease Consultants
state: Texas
city: Burlington
country: United States
facility: The University of Vermont Medical Center
state: Vermont
city: Newport News
country: United States
facility: Maryview Hospital, Inc. d/b/a Bon Secours Liver Institute of Hampton Roads
state: Virginia
city: Norfolk
country: United States
facility: Digestive and Liver Disease Specialists
state: Virginia
city: Richmond
country: United States
facility: Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours
state: Virginia
city: Richmond
country: United States
facility: McGuire VA Medical Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Roanoke
country: United States
facility: Gastroenterology Consultants of Southwest Virginia
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason - Seattle Medical Center
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Kingswood
country: Australia
facility: Nepean Blue Mountains Local Health District, Nepean Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Misericordiae Limited
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Fitzroy
country: Australia
facility: St Vincent's Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Calgary
country: Canada
facility: University of Calgary Liver Unit (Heritage Medical Research Clinic)
state: Alberta
city: Vancouver
country: Canada
facility: (G.I.R.I.) GI Research Institute
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre, Nova Scotia Health Authority
state: Nova Scotia
city: Lindsay
country: Canada
facility: Kent Place
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre-University Hospital
state: Ontario
city: North Bay
country: Canada
facility: Office of Dr. Gauthier
state: Ontario
city: Toronto
country: Canada
facility: Toronto Liver Centre
state: Ontario
city: Montreal
country: Canada
facility: Chronic Viral Illness/McGill University Health Centre (MUHC)
state: Quebec
city: Montréal
country: Canada
facility: Clinique de medecine Urbaine du Quartier Latin
state: Quebec
city: Amiens
country: France
facility: CHU Amiens Picardie
city: Angers
country: France
facility: Centre Hospitalier Universitaire d'Angers
city: Clichy
country: France
facility: Hôpital Beaujon- Service d'Hepatologie
city: La Tronche
country: France
facility: Center Hospitalier Universitaire Grenoble Alpes
city: Lyon Cedex 04
country: France
facility: Hôpital de la Croix Rousse
city: Nice
country: France
facility: CHU de Nice, Hôpital de l'Archet 2
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrierè
city: Rouen
country: France
facility: CHU de Rouen-Centre Hospitalier Universitaire
city: Strasbourg
country: France
facility: Centre Hospitalier Universitaire de Strasbourg
city: Strasbourg
country: France
facility: Hôpital Hautepierre
city: Toulouse
country: France
facility: Hôpital Purpan
city: Vandoeuvre-les-Nancy
country: France
facility: CHRU de Nancy - Hôpitaux de Brabois
city: Villejuif
country: France
facility: Hôpital Paul Brousse
city: Würzburg
country: Germany
facility: Univeritätsklinkum Würzburg
state: Bayern
city: Frankfurt am main
country: Germany
facility: Teuber Consulting & Research UG
state: Hessen
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
state: Rheinland-Pfalz
city: Leipzig
country: Germany
facility: EUGASTRO GmbH
state: Sachsen
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig AöR
state: Sachsen
city: Kiel
country: Germany
facility: Gastroenterologisch-Hepatologisches Zentrum Kiel
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charité - Universitätsmedzin Berlin
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf
city: Budapest
country: Hungary
facility: Synexus Magyarország Kft. Budapest
city: Debrecen
country: Hungary
facility: Synexus Magyarorszag Kft. Debrecen A.S.
city: Gyula
country: Hungary
facility: Synexus Magyarorszag Kft. Gyula DRS
city: Auckland
country: New Zealand
facility: Middlemore Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Public Hospital
city: Wellington
country: New Zealand
facility: Wellington Regional Hospital
city: Częstochowa
country: Poland
facility: Synexus Polska Sp. z o.o., Oddział w Częstochowie
city: Gdańsk
country: Poland
facility: Synexus Polska Sp. z.o.o., Oddział w Gdańsku
city: Gdynia
country: Poland
facility: Synexus Polska Sp. Z.o.o., Oddział w Gdyni
city: Katowice
country: Poland
facility: Synexus Polska Sp. z o.o., Oddział w Katowicach
city: Poznań
country: Poland
facility: Synexus Polska Sp. z o.o., Oddział w Poznaniu
city: Warszawa
country: Poland
facility: Synexus Polska Sp. z o.o., Oddział w Warszawie
city: Wrocław
country: Poland
facility: Synexus Polska Sp. z o.o., Oddział w Wrocławiu
city: Łódź
country: Poland
facility: Synexus Polska Sp. z o.o., Oddział w Łodzi
city: San Juan
country: Puerto Rico
facility: Latin Clinical Trial Center
city: San Juan
country: Puerto Rico
facility: Fundación de Investigación de Diego
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politécnic La Fe
city: Kyiv
country: Ukraine
facility: Medical Center of LLC Medbud-Clinic, Clinical Diagnostic Department
city: Kyiv
country: Ukraine
facility: Kyiv Railway Clinical Hospital №2 of branch "Health Center" of the Joint-Stock Company "Ukranian Railway", Day treatment department
city: Derby
country: United Kingdom
facility: Derby Teaching Hospitals NHS Foundation Trust
state: Derbyshire
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Royal Free Hospital NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust, St Mary's Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
state: Oxfordshire
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital
state: Tyne And Wear
Study officials:
References: