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

Nonalcoholic Steatohepatitis Clinical Trial

— REVERSE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03439254
• Other study ID #: 747-304
• Status: Completed
• Phase: Phase 3
• Start date: August 30, 2017
• Est. completion date: September 8, 2022

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 919
• Est. completion date: September 8, 2022
• Est. primary completion date: September 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Compensated Cirrhosis
• Fatty Liver
• Fibrosis
• Liver Cirrhosis
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis

Intervention

Drug:
• Obeticholic acid (10 mg)
Tablets administered orally once daily.
• Obeticholic acid (10 mg to 25 mg)
Tablets administered orally once daily.
• Placebo
Tablets administered orally once daily.

Locations

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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)
Primary	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)
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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)
Secondary	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)