Study Evaluating the Efficacy and Safety of Obeticholic Acid in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (REVERSE)

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

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.

Study Overview

• Status: Completed
• Conditions: Nonalcoholic Steatohepatitis; Compensated Cirrhosis
• Intervention / Treatment: Drug: Obeticholic acid (10 mg); Drug: Obeticholic acid (10 mg to 25 mg); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 919
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Blue Mountains Local Health District, Nepean Hospital
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Mater Misericordiae Limited
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2M 4Z6
      • University of Calgary Liver Unit (Heritage Medical Research Clinic)
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • (G.I.R.I.) GI Research Institute
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen Elizabeth II Health Sciences Centre, Nova Scotia Health Authority
  • Ontario
    • Lindsay, Ontario, Canada, K9V 5G6
      • Kent Place
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre-University Hospital
    • North Bay, Ontario, Canada, PIB 2H3
      • Office of Dr. Gauthier
    • Toronto, Ontario, Canada, V5Z 1H2
      • Toronto Liver Centre
  • Quebec
    • Montreal, Quebec, Canada, H4A 3JI
      • Chronic Viral Illness/McGill University Health Centre (MUHC)
    • Montréal, Quebec, Canada, H2L 4E9
      • Clinique de médecine Urbaine du Quartier Latin
• France
  • Amiens, France, 80054
    • CHU Amiens Picardie
  • Angers, France, 49933
    • Centre Hospitalier Universitaire d'Angers
  • Clichy, France, 92110
    • Hôpital Beaujon- Service d'Hepatologie
  • La Tronche, France, 38700
    • Center Hospitalier Universitaire Grenoble Alpes
  • Lyon Cedex 04, France, 69317
    • Hopital de la Croix Rousse
  • Nice, France, 06202
    • CHU de Nice, Hôpital de l'Archet 2
  • Paris, France, 75651
    • Hôpital Pitié-Salpêtrière
  • Rouen, France, 76031
    • CHU de Rouen-Centre Hospitalier Universitaire
  • Strasbourg, France, 67200
    • Hôpital Hautepierre
  • Strasbourg, France, 67000
    • Centre Hospitalier Universitaire de Strasbourg
  • Toulouse, France, 31059
    • Hopital Purpan
  • Vandoeuvre-les-Nancy, France, 54511
    • CHRU de Nancy - Hopitaux de Brabois
  • Villejuif, France, 94800
    • Hopital Paul Brousse
• Germany
  • Berlin, Germany, 13353
    • Charité - Universitätsmedzin Berlin
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg Eppendorf
  • Bayern
    • Würzburg, Bayern, Germany, 97080
      • Univeritätsklinkum Würzburg
  • Hessen
    • Frankfurt am main, Hessen, Germany, 60594
      • Teuber Consulting & Research UG
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • Universitätsmedizin Mainz
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Universitätsklinikum Leipzig AöR
    • Leipzig, Sachsen, Germany, 04103
      • Eugastro GmbH
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24146
      • Gastroenterologisch-Hepatologisches Zentrum Kiel
• Hungary
  • Budapest, Hungary, 1036
    • Synexus Magyarország Kft. Budapest
  • Debrecen, Hungary, 4025
    • Synexus Magyarorszag Kft. Debrecen A.S.
  • Gyula, Hungary, 5700
    • Synexus Magyarorszag Kft. Gyula DRS
• New Zealand
  • Auckland, New Zealand, 2025
    • Middlemore Hospital
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital
  • Dunedin, New Zealand, 6021
    • Dunedin Public Hospital
  • Wellington, New Zealand, 6021
    • Wellington Regional Hospital
• Poland
  • Częstochowa, Poland, 42-200
    • Synexus Polska Sp. z o.o., Oddział w Częstochowie
  • Gdańsk, Poland, 80-382
    • Synexus Polska Sp. z.o.o., Oddział w Gdańsku
  • Gdynia, Poland, 81-537
    • Synexus Polska Sp. Z.o.o., Oddział w Gdyni
  • Katowice, Poland, 40-040
    • Synexus Polska Sp. z o.o., Oddział w Katowicach
  • Poznań, Poland, 60-702
    • Synexus Polska Sp. z o.o., Oddział w Poznaniu
  • Warszawa, Poland, 01-192
    • Synexus Polska Sp. z o.o., Oddział w Warszawie
  • Wrocław, Poland, 50-381
    • Synexus Polska Sp. z o.o., Oddział w Wrocławiu
  • Łódź, Poland, 90-127
    • Synexus Polska Sp. z o.o., Oddział w Łodzi
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Fundacion de Investigacion de Diego
  • San Juan, Puerto Rico, 00909
    • Latin Clinical Trial Center
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen Del Rocio
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
• Ukraine
  • Kyiv, Ukraine, 03037
    • Medical Center of LLC Medbud-Clinic, Clinical Diagnostic Department
  • Kyiv, Ukraine, 03049
    • Kyiv Railway Clinical Hospital №2 of branch "Health Center" of the Joint-Stock Company "Ukranian Railway", Day treatment department
• United Kingdom
  • Derbyshire
    • Derby, Derbyshire, United Kingdom, DE22 3NE
      • Derby Teaching Hospitals NHS Foundation Trust
  • England
    • Birmingham, England, United Kingdom, B15 2TH
      • University Hospitals Birmingham NHS Foundation Trust
    • London, England, United Kingdom, SE5 9RS
      • King's College Hospital NHS Foundation Trust
    • London, England, United Kingdom, NW3 2QG
      • Royal Free Hospital NHS Foundation Trust
    • London, England, United Kingdom, W2 INY
      • Imperial College Healthcare NHS Trust, St Mary's Hospital
    • Nottingham, England, United Kingdom, NG7 2UH
      • Nottingham University Hospitals NHS Trust
    • Plymouth, England, United Kingdom, PL6 8DH
      • Derriford Hospital
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Oxford University Hospitals Nhs Foundation Trust
  • Tyne And Wear
    • Newcastle Upon Tyne, Tyne And Wear, United Kingdom, NE7 7DN
      • The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital
• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
      • Digestive Health Specialists of the Southeast
    • Madison, Alabama, United States, 35758
      • Objective GI d/b/a North Alabama GI Research Center
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Arizona Liver Health
    • Glendale, Arizona, United States, 85306
      • Arizona Liver Health
    • Tucson, Arizona, United States, 85712
      • The Institute for Liver Health
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Liver Wellness Center
    • North Little Rock, Arkansas, United States, 72117
      • Arkansas Gastroenterology
  • California
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research
    • Fresno, California, United States, 93701
      • University of California, San Francisco-Fresno
    • La Jolla, California, United States, 92037
      • Scripps Whittier Diabetes Institute
    • La Mesa, California, United States, 91942
      • eStudySite
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC
    • Los Angeles, California, United States, 90048
      • Cedars-Sinani Medical Center
    • Palm Springs, California, United States, 92262
      • Palmtree Clinical Research, Inc.
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
    • Rialto, California, United States, 92377
      • Inland Empire Liver Foundation
    • Sacramento, California, United States, 95817
      • University of California, Davis Medical Center
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Sacramento Medical Center
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver and Hospital
    • Colorado Springs, Colorado, United States, 80907
      • Peak Gastroenterology Associates
    • Englewood, Colorado, United States, 80113
      • South Denver Gastroenterology, PC
  • Florida
    • Aventura, Florida, United States, 33180
      • Innovative Medical Research of South Florida, Inc.
    • Coral Gables, Florida, United States, 33134
      • Hi Tech and Global Research LLC
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
    • Jacksonville, Florida, United States, 32207
      • UF Health Jacksonville-Gastroenterology Emerson
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Diseases/University of Miami
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare, LLC
    • Palmetto Bay, Florida, United States, 33157
      • Innovation Medical Research Center
    • Pensacola, Florida, United States, 32503
      • Gastroenterology Associates of Pensacola, PA
    • Tampa, Florida, United States, 33606
      • Tampa General Medical Group
    • Tampa, Florida, United States, 33614
      • Guardian Angel Research Center, INC
    • Zephyrhills, Florida, United States, 33542
      • Florida Medical Clinic, P.A
  • Georgia
    • Athens, Georgia, United States, 30607
      • Summit Clinical Research, LLC
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic (TEC)
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Grand Teton Research Group, PLLC
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Indiana
    • New Albany, Indiana, United States, 47150
      • Aquiant Research
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Topeka, Kansas, United States, 66606
      • Kansas Medical Clinic
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville, Clinical Trials Unit
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research, LLC
    • Monroe, Louisiana, United States, 71201
      • Delta Research Partners, LLC
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
    • Shreveport, Louisiana, United States, 71105
      • Louisiana Research Center
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
    • Bethesda, Maryland, United States, 20889
      • Walter Reed National Military Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital & Medical Center
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Health Care
  • Michigan
    • Wyoming, Michigan, United States, 49519
      • Gastroenterology Associates of Western Michigan, PLC d.b.a. West Michigan Clinical Research Center
    • Ypsilanti, Michigan, United States, 48197
      • Huron Gastroenterology Associates
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Minnesota Gastroenterology, P.A.
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
    • Jackson, Mississippi, United States, 39216
      • Southern Therapy and Advanced Research (STAR) LLC
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Research Institute
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Nebraska
    • Omaha, Nebraska, United States, 68124
      • CHI Health Alegent Creighton Clinic
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Sierra Clinical Research
  • New Jersey
    • Martinsville, New Jersey, United States, 08836
      • Amici GI-LLC
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Buffalo, New York, United States, 14203
      • University at Buffalo, Clinical and Translational Research Center
    • New York, New York, United States, 10016
      • NYU Langone Health
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • New York, New York, United States, 10003
      • Ichan School of Medicine at Mount Sinai Beth Israel
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Gastroenterology Associates, P.A.
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill, School of Medicine
    • Charlotte, North Carolina, United States, 28207
      • Charlotte Gastroenterology & Hepatology, PLLC
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Huntersville, North Carolina, United States, 28078
      • Carolinas Center for Liver Disease/Carolinas HealthCare System
    • Huntersville, North Carolina, United States, 28078
      • Carolinas Health Care System Center for Liver Disease
    • Morehead City, North Carolina, United States, 28557
      • Diabetes & Endocrinology Consultants, PC
    • Wilmington, North Carolina, United States, 28403
      • Trial Management Associates, LLC
  • Ohio
    • Beavercreek, Ohio, United States, 45440
      • Dayton Gastroenterology, Inc.
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Northeast Clinical Research Center, LLC
    • Hershey, Pennsylvania, United States, 17033
      • The Pennsylvania State University and the Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19141
      • Einstein Healthcare Network
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC - Center for Liver Diseases at the Thomas E. Starzl Institute
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • University Gastroenterology
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Ralph H. Johnson Veterans Affairs Medical Center
    • Charleston, South Carolina, United States, 29425
      • SCTR Research Nexus
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Medical Center LLP
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Hermitage, Tennessee, United States, 37076
      • Associates in Gastroenterology, PLC
    • Johnson City, Tennessee, United States, 37604
      • Johnson City Medical Center
    • Memphis, Tennessee, United States, 38104
      • Methodist Healthcare University Hospital
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center - Digestive Disease Center
    • Nashville, Tennessee, United States, 37211
      • Quaility Medical Research, PLLC
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute LLC
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75203
      • The Liver Institute At Methodist Dallas Medical Center
    • Dallas, Texas, United States, 75234
      • Liver Center of Texas
    • Dallas, Texas, United States, 75246
      • Texas Digestive Disease Consultants
    • Fort Sam Houston, Texas, United States, 78234
      • San Antonio Military Medical Center
    • Fort Worth, Texas, United States, 76104
      • Texas Digestive Disease Consultants
    • Fort Worth, Texas, United States, 76104
      • Baylor Scott and White All Saints Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Advanced Liver Therapies
    • Houston, Texas, United States, 77030
      • The University of Texas Medical School at Houston
    • McAllen, Texas, United States, 78504
      • Centex Studies, Inc.
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
    • San Antonio, Texas, United States, 78215
      • American Research Corporation
    • San Marcos, Texas, United States, 78666
      • Texas Digestive Disease Consultants
  • Vermont
    • Burlington, Vermont, United States, 05401
      • The University of Vermont Medical Center
  • Virginia
    • Newport News, Virginia, United States, 23602
      • Maryview Hospital, Inc. d/b/a Bon Secours Liver Institute of Hampton Roads
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialists
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23249
      • McGuire VA Medical Center
    • Richmond, Virginia, United States, 23226
      • Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours
    • Roanoke, Virginia, United States, 24014
      • Gastroenterology Consultants of Southwest Virginia
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98101
      • Virginia Mason - Seattle Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Obeticholic Acid (OCA) 10 mg; 10 mg OCA for up to 18 months	Drug: Obeticholic acid (10 mg); Tablets administered orally once daily.; Other Names: INT-747; 6alpha-ethylchenodeoxycholic acid (6-ECDCA); OCA
Experimental: Obeticholic Acid (OCA) 10 mg to 25 mg; 10 mg OCA for the first 3 months and then may titrate up to 25 mg OCA for the remaining 15 months of the study	Drug: Obeticholic acid (10 mg to 25 mg); Tablets administered orally once daily.; Other Names: INT-747; 6alpha-ethylchenodeoxycholic acid (6-ECDCA); OCA
Placebo Comparator: Placebo; Placebo for up to 18 months	Drug: Placebo; Tablets administered orally once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DB Phase: Number of Participants Who Were Responders and Showed Improvement in Fibrosis by at Least 1 Stage Without Worsening of Nonalcoholic Steatohepatitis (NASH)	Fibrosis stage was evaluated by NASH Clinical Research Network(CRN)Fibrosis Staging System with stages:0=no fibrosis;1=perisinusoidal/periportal;1A=mild,zone 3,perisinusoidal;1B=moderate,zone 3,perisinusoidal;1C=portal/periportal;2=perisinusoidal and portal/periportal;3=bridging fibrosis;4=cirrhosis.No worsening of steatohepatitis was defined as no worsening of lobular inflammation or hepatocellular ballooning grade as per scoring in relevant nonalcoholic fatty liver disease activity score (NAS) categories.NAS is semiquantitative scoring system based on unweighted sum of:steatosis (0=<5% to 3=>66%),lobular inflammation(0=no foci to 3=>4 foci/200x),hepatocellular ballooning(0=none to 2=many cells/prominent ballooning)scores.Total scale range:0-12;0:no features of fatty liver disease and 12:highest degree of fatty liver disease.Higher scores:worse symptoms.Responders:did not discontinue treatment due to Adverse event(AE) or did not die and had evaluable post-Baseline biopsy assessment	Up to 18 months
OLE Phase: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment.	Up to 12 months
OLE Phase: Change From Baseline to Month 12 in Liver Stiffness Measurement (LSM)	Non-invasive radiological methods to assess liver stiffness were conducted at selected study sites where the respective devices were available. These assessments were taken by vibration controlled transient elastography (TE) method using FibroScan®. Participant was included as a random effect and an unstructured covariance matrix was used assuming convergence could be attained. Baseline was defined as the last value collected prior to the first administration of the investigational product (IP). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.	Baseline and up to Month 12
OLE Phase: Fibrosis-4 (FIB-4) at Baseline	FIB-4 was a noninvasive assessment of liver disease assessed by a combination of age, alanine aminotransferase (ALT) and platelet results. FIB-4 was the ratio of age in years and aminotransferase to platelet count. It was a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, ALT, Aspartate aminotransferase (AST) and age that was calculated using formula: FIB-4 = (Age [years] x AST [Units per Liter {U/L}]) / (platelets [10^9/L] x (square root of ALT [U/L])). A FIB-4 index of <1.45 indicated no or moderate fibrosis and an index of > 3.25 indicated extensive fibrosis/cirrhosis. Higher ratio indicated worse condition. Baseline was defined as the last value collected prior to the first administration of the IP.	Baseline (Day 1)
OLE Phase: Enhanced Liver Fibrosis (ELF) at Baseline	ELF was non-invasive panel of circulating fibrosis markers calculated from serum biomarkers. The markers of fibrosis comprised hyaluronic acid (HA), tissue inhibitor of metalloproteinase (TIMP1) and procollagen III N-terminal peptide (PIIINP). Each of these markers was measured by an immunoassay and an ELF score was generated, from which a level of fibrosis severity could be determined. The ELF test was a composite score: < 7.7: no to mild fibrosis; ≥ 7.7 - < 9.8: Moderate fibrosis; ≥ 9.8 - < 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis.; higher ELF scores were associated with worsening liver fibrosis. Baseline was defined as the last value collected prior to the first administration of the IP.	Baseline (Day 1)
OLE Phase: Number of Participants Reporting All-cause Mortality	All-cause mortality is defined as death due to any cause. Number of participants reporting all-cause mortality is presented	Up to Month 12
OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Ascites, Hepatocellular Carcinoma (HCC) and Non-liver Related Death	Adjudication was performed under the review of Hepatic Safety Adjudication Committee (HSAC) of all available data for each identified participant to determine liver injury status. Number of participants with adjudicated liver related clinical outcomes for the following is presented: Ascites (secondary to cirrhosis and requiring medical intervention), Hepatocellular carcinoma (HCC) and non-liver related death.	Up to 12 months
OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Worsening of Child-Pugh Score	The Child-Pugh classification was a scoring system used for the classification of the severity of cirrhosis. It included three continuous variables (bilirubin, albumin, and international normalized ratio) and two discrete variables (ascites and encephalopathy). Each variable was scored 1-3 with 3 indicating most severe derangement. The determination of Child-Pugh score ranged from 5 to 15. The higher the score, the sicker the participant. Adjudication was performed under the review of HSAC of all available data for each identified participant to determine liver injury status. Number of participants with adjudicated liver related clinical outcomes for worsening of Child-Pugh score is presented.	Up to 12 months
OLE Phase: Number of Participants With Adjudicated Liver Related Clinical Outcomes: Model for End-Stage Liver Disease (MELD) Score ≥15	MELD was a scoring system for assessing the severity of chronic liver disease and to assess prognosis and suitability for liver transplantation. It uses the participant's values for total bilirubin, serum creatinine, and the international normalized ratio for prothrombin time to predict survival. MELD score ranges from 6 (less ill) to 40 (gravely ill) with scores and mortality probability being: Score 40=71.3% mortality; Scores 30-39=52.6% mortality; Scores 20-29=19.6% mortality; Scores10-19=6.0% mortality; Score 9 or less=1.9% mortality. Higher scores indicated greater disease severity. Adjudication was performed under the review of HSAC of all available data for each identified participant to determine liver injury status. Number of participants with adjudicated liver related clinical outcomes for MELD score ≥15 is presented.	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DB Phase: Change From Baseline to Month 18 in LSM	Non-invasive radiological methods to assess liver stiffness were conducted at selected study sites where the respective devices were available. These assessments were taken by vibration controlled TE method using FibroScan®. Participant was included as a random effect and an unstructured covariance matrix was used assuming convergence could be attained. The principal comparison was at Month 18. Baseline was defined as the last value collected prior to the first administration of the IP. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.	Baseline and up to Month 18
DB Phase: FIB-4 at Baseline	FIB-4 was a noninvasive assessment of liver disease assessed by a combination of age, ALT and platelet results. FIB-4 was the ratio of age in years and aminotransferase to platelet count. It was a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, ALT, AST and age that was calculated using formula: FIB-4 = (Age [years] x AST [U/L]) / (platelets [10^9/L] x (square root of ALT [U/L])). A FIB-4 index of <1.45 indicated no or moderate fibrosis and an index of > 3.25 indicated extensive fibrosis/cirrhosis. Higher ratio indicated worse condition. Baseline was defined as the last value collected prior to the first administration of the IP.	Baseline (Day 1)
DB Phase: ELF at Baseline	ELF was non-invasive panel of circulating fibrosis markers calculated from serum biomarkers. The markers of fibrosis comprised HA, TIMP1 and PIIINP. Each of these markers was measured by an immunoassay and an ELF score was generated, from which a level of fibrosis severity could be determined. The ELF test was a composite score: < 7.7: no to mild fibrosis; ≥ 7.7 - < 9.8: Moderate fibrosis; ≥ 9.8 - < 11.3: Severe fibrosis; ≥ 11.3: Cirrhosis.; higher ELF scores were associated with worsening liver fibrosis. Baseline was defined as the last value collected prior to the first administration of the IP.	Baseline (Day 1)

Collaborators and Investigators

• Sponsor: Intercept Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2017
• Primary Completion (Actual): September 8, 2022
• Study Completion (Actual): September 8, 2022

Study Registration Dates

• First Submitted: February 14, 2018
• First Submitted That Met QC Criteria: February 19, 2018
• First Posted (Actual): February 20, 2018

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Nonalcoholic Steatohepatitis; NASH; Compensated Cirrhosis; Fatty Liver Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Gastrointestinal Agents; Cathartics; Chenodeoxycholic Acid
• Other Study ID Numbers: 747-304

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No