Randomized Global Phase 3 Study to Evaluate the Impact on NASH With Fibrosis of Obeticholic Acid Treatment

Non Alcoholic Steatohepatitis (NASH) Clinical Trial

— REGENERATE  

Official title:

A Phase 3, Double-Blind, Randomized, Long-Term, Placebo-Controlled, Multicenter Study Evaluating the Safety and Efficacy of Obeticholic Acid in Subjects With Nonalcoholic Steatohepatitis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02548351
• Other study ID #: 747-303
• Status: Terminated
• Phase: Phase 3
• Start date: September 22, 2015
• Est. completion date: September 15, 2023

Study information

• Verified date: October 2023
• Source: Intercept Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objectives of this study are to evaluate the effect of Obeticholic Acid treatment compared to placebo on 1) histological improvement and 2) liver-related clinical outcomes in patients with non-cirrhotic nonalcoholic steatohepatitis (NASH) with liver fibrosis.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2480
• Est. completion date: September 15, 2023
• Est. primary completion date: September 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Histologic evidence of NASH upon central read of a liver biopsy obtained no more than 6 months before Day 1 defined by presence of all 3 key histological features of NASH according to NASH CRN criteria.

2. Histologic evidence of fibrosis stage 2 or stage 3 as defined by the NASH CRN scoring of fibrosis, or Histologic evidence of fibrosis stage 1a or stage 1b if accompanied by =1 of the

following risk factors:

• Obesity (BMI =30 kg/m2)
• Type 2 diabetes diagnosed per 2013 American Diabetes Association criteria
• ALT >1.5× upper limit of normal (ULN).

3. For subjects with a historical biopsy, is either not taking or is on stable doses of TZDs/glitazones or vitamin E for 6 months before Day 1.

4. Stable body weight.

Exclusion Criteria:

1. Model for End-stage Liver Disease (MELD) score >12

2. ALT =10× ULN

3. HbA1c >9.5%

4. Total bilirubin >1.5 mg/dL

5. Evidence of other known forms of known 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)

6. History of liver transplant, or current placement on a liver transplant list

7. Current or history of significant alcohol consumption

8. Prior or planned ileal resection, or prior or planned bariatric surgery

9. Histological presence of cirrhosis

10. History of biliary diversion

11. Known positivity for human immunodeficiency virus infection.

12. Acute cholecystitis or acute biliary obstruction.

13. BMI >45 kg/m2

Related Conditions & MeSH terms

• Fatty Liver
• Non Alcoholic Steatohepatitis (NASH)
• Non-alcoholic Fatty Liver Disease

Intervention

Drug:
• Obeticholic Acid

• Placebo

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital Gastroenterology and Hepatology Dept.	Adelaide
Australia	Flinders Medical Centre	Bedford Park
Australia	AW Morrow Gastroenterology and Liver Centre Royal Prince Alfred Hospital	Camperdown
Australia	Monash Health - Monash Medical Centre	Clayton
Australia	Gallipoli Medical Research Foundation	Greenslopes
Australia	Austin Hospital	Heidelberg
Australia	Royal Brisbane and Women's Hospital	Herston
Australia	Nepean Hospital	Kingswood
Australia	The Alfred Hospital, Department of Gastroenterology	Melbourne
Australia	Fiona Stanley Hospital	Murdoch
Australia	The Royal Melbourne Hospital	Parkville
Australia	Westmead Hospital	Westmead
Austria	Universitätsklinik für Innere Medizin I Innsbruck	Innsbruck
Austria	Klinikum Klagenfurt am Wörthersee	Klagenfurt
Austria	Ordensklinikum Linz GmbH	Linz
Austria	Uniklinikum Salzburg	Salzburg
Austria	Medizinische Universität Wien	Wien
Belgium	AZ Sint-Jan Brugge Oostende	Brugge
Belgium	UCL Saint-Luc - Hepatology Department	Brussels
Belgium	ULB H?pital Erasme - Gastroenterology	Brussels	Brabant
Belgium	UZ Antwerpen	Edegem	Antwerpen
Belgium	Ziekenhuis Oost-Limburg (ZOL)	Genk
Belgium	UZ Gent Gastroenterology Department	Ghent
Belgium	UZ Leuven Campus Gathuisberg Hepatology Department	Leuven	Vlaams-Brabant
Belgium	AZ Nikolaas	Sint-Niklaas
Canada	University of Calgary Liver Unit	Calgary
Canada	GI Research	Edmonton
Canada	University of Alberta	Edmonton
Canada	London Health Sciences Centre University Hospital	London	Ontario
Canada	Centre de Recherche du Centre Hospitalier de l'Universite de Montreal	Montreal
Canada	The Research Institute of the McGill University Health Centre	Montreal
Canada	Toronto Center for Liver Disease	Toronto
Canada	Toronto Liver Centre	Toronto
Canada	GIRI - GI Research Institute	Vancouver
Canada	Gordon and Leslie Diamond Health Care Centre	Vancouver
Canada	LAIR Centre	Vancouver
Canada	PerCuro Clinical Research Ltd.	Victoria
Canada	John Buhler Research Centre	Winnipeg
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital Medicinsk Hepatogastroenterologisk Afdeling	Aarhus
Denmark	Copenhagen University Hospital Hvidovre	Hvidovre
Denmark	Odense University Hospital	Odense
Finland	Helsinki University Hospital	Helsinki
Finland	Turku University Hospital	Turku
France	CHU Amiens Picardie	Amiens
France	CHU Angers-Service d'Hepato-Gastroenterologie	Angers
France	Centre hospitalier Pierre Oudot	Bourgoin-Jallieu
France	CHU Beaujon-Service d'Hépatologie	Clichy
France	Hôpital Henri Mondor - Service d'hépatologie	Creteil
France	CHU Grenoble	Grenoble
France	CHRU Hôpital Claude Huriez	Lille
France	Hôpital de la Croix Rousse	Lyon
France	Hôpital Saint Joseph	Marseille
France	Hôpital de l'Archet II-CHU Nice	Nice
France	Service d'Hepato-Gastroenterologie CHR Orleans - La Source	Orléans
France	Hôpital Cochin	Paris
France	Hôpital de la Pitié Salpétrère	Paris
France	Hospital Saint Antoine Department of Hepatology	Paris
France	Hopital Haut-Lévêque-Hépatogastroentérologie-Bât USN	Pessac
France	CHU de Rouen	Rouen
France	CHU Toulouse - Hopital de Purpan	Toulouse
France	CHU de Nancy - Hôpital de Brabois adultes	Vandoeuvre-Lès-Nancy
France	Hopital Paul Brousse	Villejuif
Germany	Universitatsklinikum Aachen, RWTH Aachen, Medizinische Klinik III	Aachen
Germany	Charite Universitätsmedizin Campus Virchow	Berlin
Germany	St. Josef-Hospital, Ruhr University Bochum	Bochum
Germany	University Hosptial Cologne Clinics for Gastroenterology and Hepatology	Cologne
Germany	Friedrich-Alexander-Universität Erlangen Medizinische Klinik 1	Erlangen	Bavaria
Germany	Katholische Kliniken Ruhrhalbinsel GmbH	Essen
Germany	University Hospital Essen	Essen
Germany	Universitätsklinikum Hamburg- Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Heidelberg Medizinischen Klinik IV Gastroenterologie und Hepatologie	Heidelberg	Baden-Wurttemberg
Germany	Gastroenterologische Gemeinschaftspraxis	Herne
Germany	Hepato-Gastroenterology Center Kiel	Kiel
Germany	EUGASTRO GmbH	Leipzig
Germany	Universitätsklinikum Leipzig Klinik für Gastroenterologie und Rheumatologie-Sektion Hepatologie	Leipzig	Saxony
Germany	Universitätsmedizin Mainz, I. Med. Klinik und Poliklinik	Mainz	Rhineland-Palatinate
Germany	Krankenhaus Barmherzige Bruder Innere Medizin I - Gastroenterologie	Munich
Germany	Universitätsklinikum Würzburg	Würzburg
Hungary	Egyesitett Szent Istvan és Szent Laszlo	Budapest
Hungary	Pecsi Tudomanyegyetem Klinikai Kozpont, I. sz	Budapest
Hungary	Kenezy Gyula Korhaz es Rendelointezet	Debrecen
Israel	Soroka Medical Center Division of Internal Medicine	Be'er Sheva
Israel	Carmel Medical Center	Haifa
Israel	Rambam Medical Center Center for Liver diseases	Haifa
Israel	Hadassah Ein Kerem MC	Jerusalem
Israel	Shaarei Zedek Medical Center	Jerusalem
Israel	West Galilee Hospital	Nahariya
Israel	Holy Family Medical Center	Nazareth
Israel	Rabin Medical Center, Liver Institute	Petach Tikva
Israel	Sheba Medical Center	Ramat Gan
Israel	Sourasky Tel-Aviv Medical Center	Tel Aviv
Italy	Universita di Bologna - DIMEC	Bologna
Italy	University di Bologna - Dipartimento di Scienze Mediche e Chirurgiche - DIMEC	Bologna
Italy	Ospedale san Giuseppe - Multimedica	Milan
Italy	Azienda Socio-Sanitaria Territoriale (ASST) Santi Paolo e Carlo	Milano
Italy	Fondazione IRCCS Ca Granda Ospedale	Milano
Italy	Fondazione IRCCS Ca Grande Ospedale	Milano
Italy	AOU di Modena Ospedale Civile	Modena
Italy	Azienda Ospedaliera Universitaria Policlinico	Napoli
Italy	Policlinico Paolo Giaccone di Palermo	Palermo
Italy	Policlinico University Campus Biomedico	Rome
Italy	Istituto Clinico Humanitas	Rozzano
Italy	A.O.U. Città della Salute e della Scienza di Torino	Torino
New Zealand	Middlemore Hospital	Auckland
New Zealand	NZ Liver Transplant Unit	Grafton	Auckland
Poland	Centrum Badan Klinicznych PI-House Sp. z o.o.	Gdansk
Poland	Uniwersyteckie Centrum Kliniczne im. Prof K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowicach	Katowice
Poland	Wojewodzki Specjalistyczny Szpital im. Dr WI. Bieganskiego	Lodz
Poland	Samodzielny Publiczny Szpital Kliniczny Nr 1	Lublin
Poland	Centrum Badan Klinicznych Piotr Napora	Wroclaw
Portugal	Centro Hospitalar do Baixo Vouga, E.P.E.	Aveiro
Portugal	Ulsba, Epe	Beja
Portugal	Hospital da Senhora da Oliveira - Guimarães	Guimarães
Portugal	Centro Hospitalar de Lisboa Norte, EPE - Hosp. de Santa Maria	Lisboa
Portugal	Centro Hospitalar Lisboa Ocidental	Lisbon
Puerto Rico	Ave Ponce De Leon #715	San Juan
Puerto Rico	Fundacion de Investigacion	San Juan
Puerto Rico	Klinical Investigations Group, LLC	San Juan
Serbia	Clinical Hospital Center Bezanijska Kosa	Belgrade
Serbia	University Medical Centar Zvezdara	Belgrade
Serbia	Clinical Center Nis	Nis
Spain	Hospital Universitario Fundación Alcorcon	Alcorcón
Spain	Hospital General y Universitario de Alicante	Alicante
Spain	Hospital Clinic(o) de Barcelona	Barcelona
Spain	Hospital del Mar Gastroenterology Department	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Complejo Asistencial Universitario de Leon	Leon
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Hospital (Universitario) Virgen de la Victoria	Malaga
Spain	Hospital Universitari Son Espases	Palma de Mallorca	Baleares
Spain	Hospital Universitario Donostia	San Sebastian
Spain	Hospital (Universitario) Marqués de Valdecilla	Santander
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Consorcio Hospital General Universitario	Valencia
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitario La Fe.	Valencia
Spain	Hospital Universitario Miguel Servet	Zaragoza
Sweden	Sahlgrenska University Hospital	Gothenburg
Sweden	Universitetsjukhuset Linkoping	Linkoping
Sweden	Karolinska University Hospital	Stockholm
Switzerland	UVCM Hepatologie	Bern
Switzerland	Epatocentro Ticino	Lugano
Switzerland	Hospital of St. Gallen	St.Gallen
Switzerland	University Clinic of Gastroenterology & Hepatology	Zürich
United Kingdom	Institute of Biomedical Research	Birmingham
United Kingdom	Royal Bournemouth Hospital	Bournemouth	Dorset
United Kingdom	Bradford Royal Infirmary	Bradford
United Kingdom	University Hospital Bristol NHS Foundation Trust	Bristol
United Kingdom	Cambridge University Hospital	Cambridge
United Kingdom	University Hospitals Coventry & Warwickshire	Coventry
United Kingdom	Glasgow Royal Infirmary, NHS Greater	Glasgow
United Kingdom	Royal Surrey NHS Foundation Trust	Guildford	Surrey
United Kingdom	John Radcliffe Hospital	Headington	Oxford
United Kingdom	Gastroenterology Department Hull Royal Infirmary	Hull
United Kingdom	University Hospital Aintree	Liverpool
United Kingdom	Guy's and St. Thomas NHS Foundation Trust	London
United Kingdom	Institute for Liver and Digestive Health	London
United Kingdom	Royal London Hospital	London
United Kingdom	St. Mary's Hospital	London
United Kingdom	Central Manchester University Hospital NHS Foundation Trust Manchester Royal Infirmary	Manchester
United Kingdom	The Newcastle Upon Tyne Hospitals NHS Foundation Trust	Newcastle Upon Tyne
United Kingdom	Norfolk and Norwich University Hospitals	Norwich	Norfolk
United Kingdom	Nottingham Digestive Diseases and Biomedical Research Unit	Nottingham
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Queen Alexandra Hospital	Portsmouth	Hampshire
United Kingdom	Royal Cornwall Hospital	Truro	Cornwall
United States	AccumetRx Clinical research / UGNM	Albuquerque	New Mexico
United States	Investigative Clinical Research	Annapolis	Maryland
United States	Texas Clinical Research Institute	Arlington	Texas
United States	Asheville Gastroenterology Associates, PA	Asheville	North Carolina
United States	Summit Clinical Research, LLC	Athens	Georgia
United States	Digestive Healthcare of Georgia	Atlanta	Georgia
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	The Emory Clinic (TEC)	Atlanta	Georgia
United States	University of Colorado Denver and Hospital	Aurora	Colorado
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Mercy Medical Center	Baltimore	Maryland
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	The University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The Medical Center of Bowling Green	Bowling Green	Kentucky
United States	Montefiore Medical Center	Bronx	New York
United States	University at Buffalo, Clinical and Translational Research Center	Buffalo	New York
United States	Lahey Hospital & Medical Center	Burlington	Massachusetts
United States	The University of Vermont Medical Center - Smith 2	Burlington	Vermont
United States	Institute for Liver Health DBA Arizona Liver Health	Chandler	Arizona
United States	University of North Carolina at Chapel Hill, School of Medicine	Chapel Hill	North Carolina
United States	Center for Liver Disease	Charlotte	North Carolina
United States	Charlotte Gastroenterology & Hepatology	Charlotte	North Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	WR-Clinsearch, LLC	Chattanooga	Tennessee
United States	Northwestern University, Feinberg School of Medicine	Chicago	Illinois
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	GW Research Inc.	Chula Vista	California
United States	Precision Research Institute	Chula Vista	California
United States	Consultants for Clinical Research	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Southern California Research Center	Coronado	California
United States	Citrus Valley Gastroenterology	Covina	California
United States	Liver Center of Texas	Dallas	Texas
United States	Texas Digestive Disease Consultants	Dallas	Texas
United States	The Liver Institute at Methodist Dallas Medical Center	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Integrity Clinical Research, LLC	Doral	Florida
United States	Digestive Health Specialists of the Southeast	Dothan	Alabama
United States	Doylestown Health Gastroenterology	Doylestown	Pennsylvania
United States	Duke University Medical Center	Durham	North Carolina
United States	AGA Clinical Research Associates, LLC	Egg Harbor Township	New Jersey
United States	TriWest Research Associates, LLC	El Cajon	California
United States	MedResearch, Inc.	El Paso	Texas
United States	South Denver Gastroenterology, PC	Englewood	Colorado
United States	Inova Fairfax Medical Campus	Falls Church	Virginia
United States	Cumberland Research Associates, LLC	Fayetteville	North Carolina
United States	Hillmont GI, pc	Flourtown	Pennsylvania
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Baylor Scott & White All Saints Medical Center	Fort Worth	Texas
United States	Texas Digestive Disease Consultants	Fort Worth	Texas
United States	Fresno Clinical Research Center	Fresno	California
United States	UCSF Fresno, Clinical Research Center	Fresno	California
United States	UF Hepatology Research at CTRB	Gainesville	Florida
United States	Gastro One	Germantown	Tennessee
United States	Arizona Liver Health - Glendale	Glendale	Arizona
United States	Prisma Health- Upstate Gastroenterology and Liver Center	Greenville	South Carolina
United States	Associates in Gastroenterology, PLC	Hermitage	Tennessee
United States	The Pennsylvania State University and The Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	The Queen's Medical Center - Liver Center	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	Baylor College of Medicine Ben Taub General Hospital	Houston	Texas
United States	Centex Studies, Inc.	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	Liver Associates of Texas, P.A.	Houston	Texas
United States	The University of Texas Health Science Center at Houston-Medical School IM-Division of Gastroenterology, Hepatology & Nutrition	Houston	Texas
United States	Carolinas Center for Liver Disease/Carolinas HeatlhCare System	Huntersville	North Carolina
United States	Grand Teton Research Group	Idaho Falls	Idaho
United States	Indiana University Health University Hospital	Indianapolis	Indiana
United States	Indianapolis Gastroenterology & Hepatology	Indianapolis	Indiana
United States	Nature Coast Clinical Research	Inverness	Florida
United States	Clinical Research Solutions	Jackson	Tennessee
United States	Southern Therapy and Advanced Research, LLC	Jackson	Mississippi
United States	Mayo Clinic	Jacksonville	Florida
United States	UF Health Jacksonville-Gastroenterology Emerson	Jacksonville	Florida
United States	East Tennesse Research Institute	Johnson City	Tennessee
United States	Kansas City Research Institute	Kansas City	Missouri
United States	Kansas City VA Medical Center	Kansas City	Missouri
United States	The University of Kansas Medical Center	Kansas City	Kansas
United States	Scripps Clinic	La Jolla	California
United States	University of California, San Diego	La Jolla	California
United States	Florida Digestive Health Specialist Research Institute	Lakewood Ranch	Florida
United States	Hillmont G.I. - Lansdale Office	Lansdale	Pennsylvania
United States	Sunrise Medical Research, Inc.	Lauderdale Lakes	Florida
United States	University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Liver Wellness Center	Little Rock	Arkansas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Gastrointestinal Biosciences	Los Angeles	California
United States	Keck Medical Center of USC	Los Angeles	California
United States	National Research Institute, Wilshire	Los Angeles	California
United States	Veteran Affairs Great Los Angeles Healthcare System	Los Angeles	California
United States	University of Louisville Medical, Clinical Trials Unit	Louisville	Kentucky
United States	University of Wisconsin Hospital & Clinics	Madison	Wisconsin
United States	Meridien Research	Maitland	Florida
United States	Gastrointestinal Specialists of Georgia	Marietta	Georgia
United States	Amici Clinical Research	Martinsville	New Jersey
United States	Amici GI - LLC	Martinsville	New Jersey
United States	Loyola University Medical Center	Maywood	Illinois
United States	Centex Studies, Inc.	McAllen	Texas
United States	Methodist Healthcare, University Hospital	Memphis	Tennessee
United States	Bruce W. Carter Miami VA Medical Center	Miami	Florida
United States	Janus Clinical Research, Inc.	Miami	Florida
United States	ProLive Medical Research	Miami	Florida
United States	Schiff Center for Liver Diseases	Miami	Florida
United States	Minnesota Gastroenterology	Minneapolis	Minnesota
United States	Nashville Gastrointestinal Specialists	Nashville	Tennessee
United States	Quality Medical Research, PLLC	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Tulane Medical Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Concorde Medical Group PLLC	New York	New York
United States	Icahn School of Medicine at Mt. Sinai	New York	New York
United States	Mount Sinai Beth Israel	New York	New York
United States	New York University (NYU) Langone Medical Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Rutgers University New Jersey Medical School	Newark	New Jersey
United States	Digestive and Liver Disease Specialists	Norfolk	Virginia
United States	Arkansas Gastroenterology	North Little Rock	Arkansas
United States	Sensible Healthcare, LLC	Ocoee	Florida
United States	INTEGRIS Baptist Medical Center	Oklahoma City	Oklahoma
United States	CHI Health Alegent Creighton Clinic Gastroenterology	Omaha	Nebraska
United States	Florida Hospital Transplant Institute	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Saint Joseph's Regional Medical Center	Paterson	New Jersey
United States	Drexel University	Philadelphia	Pennsylvania
United States	Einstein Healthcare Network	Philadelphia	Pennsylvania
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	UPMC	Pittsburgh	Pennsylvania
United States	University Gastroenterology	Providence	Rhode Island
United States	Rapid City Medical Center	Rapid City	South Dakota
United States	Inland Empire Liver Foundation	Rialto	California
United States	Bon Secours St. Mary's Hospital	Richmond	Virginia
United States	McGuire DVAMC GI	Richmond	Virginia
United States	Virginia Commonwealth University Clinical Research Services Unit (CRSU)	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California Davis Medical Center	Sacramento	California
United States	Saint Louis University Gastroenterology & Hepatology	Saint Louis	Missouri
United States	Washington University School of Medicine - Gastroenterology	Saint Louis	Missouri
United States	University of Utah Hospital	Salt Lake City	Utah
United States	American Research Corporation at the Texas Liver Institute	San Antonio	Texas
United States	Gastroenterology Consultants of San Antonio	San Antonio	Texas
United States	eStudy Site	San Diego	California
United States	Kaiser Permanente	San Diego	California
United States	Medical Associates Research Group	San Diego	California
United States	California Pacific Medical Center (CPMC)	San Francisco	California
United States	Quest Clinical Research	San Francisco	California
United States	UCSF/ San Francisco General Hospital	San Francisco	California
United States	University of California, San Francisco	San Francisco	California
United States	Silicon Valley Research Institute	San Jose	California
United States	Texas Digestive Disease Consultants - San Marcos	San Marcos	Texas
United States	Liver Institute Northwest	Seattle	Washington
United States	Swedish Organ Transplant and Liver Center	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Virginia Mason - Seattle Medical Center	Seattle	Washington
United States	Louisiana Research Center, LLC	Shreveport	Louisiana
United States	Arizona Liver Clinic - Tucson	Tucson	Arizona
United States	South Florida Center of Gastroenterology, P.A.	Wellington	Florida
United States	Western States Clinical Research, Inc.	Wheat Ridge	Colorado
United States	Digestive Health Specialists, PA	Winston-Salem	North Carolina
United States	University of Massachusetts Medical School	Worcester	Massachusetts
United States	Gastroenterology Associates of Western Michigan, d.b.a West Michigan Clinical Research	Wyoming	Michigan
United States	Huron Gastroenterology Associates/Center for Digestive Care	Ypsilanti	Michigan
United States	Florida Medical Clinic, P.A.	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Intercept Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Denmark,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  New Zealand,  Poland,  Portugal,  Puerto Rico,  Serbia,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the effect of Obeticholic Acid compared to placebo on liver histology in non-cirrhotic nonalcoholic steatohepatitis (NASH) subjects with stage 2 or 3 fibrosis by assessing the following primary endpoints	Primary endpoints include: The proportion of Obeticholic Acid treated patients relative to placebo achieving at least one stage of liver fibrosis improvement with no worsening of NASH, or; The proportion of Obeticholic Acid treated patients relative to placebo achieving NASH resolution with no worsening of liver fibrosis.	Measurements at Baseline and 18 months
Primary	To evaluate the effect of Obeticholic Acid compared to placebo on all-cause mortality and liver-related clinical outcomes as measured by the time to first occurrence of any of the listed adjudicated events (clinical outcomes composite endpoint)	Primary endpoint events include: Death (all cause), model of end stage liver disease (MELD) score =15, liver transplant, ascites requiring medical intervention, histological progression to cirrhosis, hospitalization (as defined by a stay of =24 hours) for onset of: variceal bleed, hepatic encephalopathy, spontaneous bacterial peritonitis.	Time to accrue a pre-specified number of adjudicated events, End of Study, estimated to be 7 years
Secondary	To evaluate the effect of Obeticholic Acid compared to placebo on liver histology in NASH	Improvement of fibrosis by at lease 1 stage AND/OR resolution of NASH, without worsening of either; No worsening of fibrosis AND no worsening of NASH; Improvement in each histological feature of NASH by at least 1 point; Improvement of fibrosis by at least 2 stages; Improvement in NAS by at least 2 points with no worsening of fibrosis; Improvement of fibrosis and resolution of NASH as a composite endpoint and as defined by both endpoints being met in the same subject; Resolution of fibrosis; Histological progression to cirrhosis	18 month Interim Analysis
Secondary	To evaluate the effect of Obeticholic Acid compared to placebo on liver histology in NASH	Improvement in fibrosis by at least 1 stage with no worsening of NASH; NASH resolution with no worsening of fibrosis; Improvement of fibrosis by at lease 1 stage AND/OR resolution of NASH, without worsening of either; No worsening of fibrosis AND no worsening of NASH; Improvement in each histological feature of NASH by at least 1 point; Improvement of fibrosis by at least 2 stages; Improvement in NAS by at least 2 points with no worsening of fibrosis; Improvement of fibrosis and resolution of NASH as a composite endpoint and as defined by both endpoints being met in the same subject; Resolution of fibrosis	End of Study, estimated to be 7 years
Secondary	To evaluate the effect of Obeticholic Acid compared to placebo on liver biochemistry and markers of liver function		18 months and End of Study, estimated to be 7 years