AURORA: A Study for the Efficacy and Safety of Cenicriviroc (CVC) for the Treatment of Liver Fibrosis in Adults With Nonalcoholic Steatohepatitis (NASH)

Nonalcoholic Steatohepatitis Clinical Trial

— AURORA  

Official title:

AURORA: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Cenicriviroc for the Treatment of Liver Fibrosis in Adult Subjects With Nonalcoholic Steatohepatitis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03028740
• Other study ID #: 3152-301-002
• Secondary ID: 2016-004566-2610
• Status: Terminated
• Phase: Phase 3
• Start date: April 5, 2017
• Est. completion date: March 9, 2021

Study information

• Verified date: November 2021
• Source: Tobira Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The AURORA study will be conducted to confirm the efficacy and safety of cenicriviroc (CVC) for the treatment of liver fibrosis in adult participants with NASH.

Description:

The AURORA study will be conducted in 2 parts. Part 1 will examine the surrogate endpoint of improvement in fibrosis of at least 1 stage (nonalcoholic steatohepatitis clinical research network [NASH CRN]) and no worsening of steatohepatitis at Month 12. Participants from Part 1 will continue into Part 2 and additional participants will be newly randomized in Part 2 to determine long-term clinical outcomes composed of histopathologic progression to cirrhosis, liver-related clinical outcomes, and all-cause mortality.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1778
• Est. completion date: March 9, 2021
• Est. primary completion date: January 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male and female participants aged between 18-75 years

• Ability to understand and sign a written informed consent form (ICF)

• Histological evidence of NASH based on central reading of the Screening biopsy

• Participants included in Part 1 must have histopathological evidence of Stage 2 or 3 liver fibrosis per the NASH CRN System based on central reading of the Screening biopsy slides. Participants newly randomized in Part 2 must have histological evidence of Stage 3 liver fibrosis per the NASH CRN System, based on central reading of the Screening period biopsy slides. Historical biopsy can be used, provided the criteria listed on Item 3a above are fulfilled.

• Females of childbearing potential and males participating in the study must agree to use at least 2 approved methods of contraception throughout the duration of the study and for 30 days after stopping study drug. Females who are postmenopausal must have documentation of cessation of menses for =12 months and serum follicle-stimulating hormone (FSH) =30 milliunits (mU)/milliliter (mL) at Screening.

Exclusion Criteria:

• Inability to undergo a liver biopsy

• Hepatitis B surface antigen (HBsAg) positive

• Hepatitis C antibody (HCVAb) positive

• Human immunodeficiency virus (HIV)-1 or HIV-2 infection

• Prior or planned liver transplantation

• Other known causes of chronic liver disease

• History or presence of cirrhosis and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding

• Alcohol consumption greater than 21 units/week for males or 14 units/week for females

• Aspartate transaminase (AST) >200 International units (IU)/liter (L) in males and females at Screening

• Alanine transaminase (ALT) >250 IU/L in males and >200 IU/L in females at Screening

• Hemoglobin A1c (HbA1c) >10% at Screening

• Serum albumin <3.5 gram (g)/deciliter (dL) at Screening

• Estimated glomerular filtration rate (eGFR) < 50 mL/minute (min)/1.73 meter (m)^2 according to the Modification of Diet in Renal Disease (MDRD) equation

• Platelet count <100,000/millimeter (mm)^3

• Total bilirubin >1.5 milligram (mg)/dL

• International normalized ratio (INR) >1.3

• Model of end stage liver disease (MELD) score >12

• Weight reduction, defined as =7% of body weight, through bariatric surgery in the past 5 years or bariatric surgery planned during the conduct of the study (including gastric banding and sleeve surgery)

• History of malignancy within the past 5 years or ongoing malignancy other than basal cell carcinoma, or resected noninvasive cutaneous squamous cell carcinoma

• Active, serious infections that require parenteral antibiotic or antifungal therapy within 30 days prior to Screening Visit

• Clinically significant cardiovascular or cerebrovascular disease within the past 3 months

• Females who are pregnant or breastfeeding

• Current or anticipated treatment with radiation therapy, cytotoxic chemotherapeutic agents and immunomodulating agents (eg, interleukins, interferons, cyclosporine, tacrolimus) except for vaccines or short-term corticosteroids

• Receiving a glucagon-like peptide 1 (GLP-1) receptor agonist, a dipeptidyl peptidase 4 (DPP-4) inhibitor, a sodium-glucose cotransporter 2 (SGLT2) and/or sodium-glucose cotransporter (SGLT1) inhibitor, or a thiazolidinedione (TZD) for less than 6 months prior to the Screening period liver biopsy. Participants on a stable therapy with a GLP-1 receptor agonist, DPP-4 inhibitor, SGLT1 and/or SGLT2 inhibitor, or a TZD for at least 6 months prior to the Screening liver biopsy may be considered eligible. (Important Note: if a historical biopsy is to be used, participants need to be on stable therapy for at least 6 months prior to the day historical liver biopsy was performed).

Related Conditions & MeSH terms

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

Intervention

Drug:
• Placebo
Cenicriviroc placebo-matching, tablet, orally, once daily for up to approximately 40 months.
• Cenicriviroc
Cenicriviroc, 150 mg, tablet, orally, once daily for up to approximately 40 months.

Locations

Country	Name	City	State
Australia	Flinders Medical Center	Adelaide	South Australia
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Saint George Hospital	Kogarah	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Austria	Universitatsklinik far Innere Medizin	Graz	Styria
Austria	Universitatsklinik far Innere Medizin II	Innsbruck	Tyrol
Austria	Klinikum Wels-Grieskirchen	Wels	Upper Austria
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Hôpital Erasme	Bruxelles	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem	Antwerpen
Belgium	Algemeen Ziekenhuis Maria Middelares	Gent	Oost-Vlaanderen
Belgium	Universitair Ziekenhuis Gent	Gent	Oost-Vlaanderen
Belgium	Centre Hospitalier Chretien CHC	Liege
Brazil	Hospital das Clínicas da Universidade Federal de Minas Gerais	Belo Horizonte	Minas Gerais
Brazil	Hospital Universitário Clementino Fraga Filho	Rio de Janeiro
Brazil	Faculdade de Medicina de São José do Rio Preto Hospital de Base	São José do Rio Preto	Sao Paulo
Brazil	Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	Sao Paulo
Canada	William Osler Health Centre, Brampton Memorial Hospital Campus	Brampton	Ontario
Canada	University of Calgary Liver Unit	Calgary	Alberta
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	Bailey Health Clinic	Edmonton	Alberta
Canada	Toronto Liver Centre	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
Chile	Centro de Investigaciones Clínicas Viña del Mar	Viña del Mar	Valparaiso
France	Hapital Sud Service d'Hepato- Gastroentarologie	Amiens Cedex 1	Picardie
France	Center Hospitalier Universitaire d'Angers	Angers	Pays De La Loire
France	Centre Hospitalier Regional et Universitaire de Besancon - L'Hopital Jean Minjoz	Besançon cedex	Franche-Comte
France	Hopital Avicenne	Bobigny
France	Centre Hospitalier Universitaire Estaing	Clermont-Ferrand	Aubergne
France	Departement d'Hacpatologie	Clichy	Ile-De-France
France	Centre Hospitalier Universitaire Grenoble	Grenoble Cedex 09	Rhone-Alpes
France	CHU de Montpellier	Montpellier cedex 5	Languedoc-Roussillon
France	Centre Hospitalier Universitaire de Nice Hôpital l'Archet	Nice Cedex 3	Provence Alpes Cote D'Azur
France	Hôpital Saint Antoine	Paris Cedex 12	Ile-de-France
France	CHU De Bordeaux - Hôpital Haût-Lévèque CMC Magellan Unita de Recherche Clinique	Pessac	Aquitaine
France	Centre Hospitalier Universitaire de Rennes- Hôpital Pontchaillou	Rennes	Bretagne
France	Centre Hospitalier Universitaire de Rouen CHU de Rouen Hopital Charles-Nicolle	Rouen	Normandie
France	CHU de Strasbourg	Strasbourg cedex	Alsace
Germany	Uniklinik RWTH Aachen	Aachen	Nordrhein-Westfalen
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	Praxis Driesener Strasse	Berlin
Germany	Synexus Clinical Research GmbH, Prüfzentrum Berlin	Berlin
Germany	Synexus Clinical Research GmbH, Prüfzentrum Frankfurt	Frankfurt	Hessen
Germany	Universitätsklinikum Hamburg Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover	Niedersachsen
Germany	Gastroenterologische Gemeinschaftspraxis	Herne	Nordhein-Westfalen
Germany	Universitätsklinikum des Saarlandes	Homburg	Saarland
Germany	Uniklinik Köln	Köln	Nordrhein-westfalen
Germany	Universitätsklinikum Leipzig	Leipzig	Sachsen
Germany	Universitätsmedizin der Johannes Gutenberg Universität Mainz	Mainz	Rheinland-Pfalz
Germany	Philipps-Universität und Universitätsklinikum Gießen und Marburg GmbH	Marburg	Hessen
Greece	Thomopoulos Gastroenterology Dept.	Patra	Peloponnese
Greece	Hippokratio Hospital	Thessaloniki
Hong Kong	Alice Ho Miu Ling Nethersole Hospital	Shatin	New Territories
Hong Kong	Prince of Wales Hospital	Shatin	New Territories
Hungary	SYNEXUS Magyarország Kft. - Budapest DRS	Budapest
Hungary	Synexus Magyarorszag Egeszsegugyi Szolgaltato Kft	Debrecen
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház	Kaposvár	Somogy
Israel	Carmel Medical Center	Haifa
Israel	Rambam Health Care Campus - Rambam Medical Center	Haifa
Israel	Hadassah Medical Center, Institute of Gastroenterology and Liver Diseases	Jerusalem
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Galilee Medical Center	Nahariya
Israel	EMMS MC	Nazareth	Jerusalem
Israel	Rabin Medical Center Beilinson Hospital	Petah Tikva
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	Sheba Medical Center	Tel-Hashomer
Italy	Azienda Ospedaliera Universitaria Careggi SOD Medicina Interna ed Epatologia	Firenze
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milan	Milano
Italy	ASST Santi Paolo e Carlo	Milano
Italy	Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Fondazione Policlinico Tor Vergata	Roma
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Italy	Istituto Clinico Humanitas	Rozzano	Milano
Italy	Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia
Latvia	Pauls Stradins Clinical University Hospital	Riga
Mexico	JM Research - Cuernavaca	Cuernavaca	Morelos
Mexico	Consultorio Dra. Maria Sarai Gonzalez Huezo	Metepec
Mexico	Consultorio Médico Dr. Alma Laura Ladron de Guevara	Mexico	Distrito Federal
Mexico	Investigaciones Medicas Cisneros	Monterrey	Nuevo Leon
New Zealand	Auckland City Hospital	Grafton	Auckland
New Zealand	Middlemore Clinical Trials	Papatoetoe	Auckland
Norway	Oslo Universitetssykehus-Ullevål	Oslo
Poland	Szpital Specjalistyczny Nr 1 w Bytomiu	Bytom	Slaskie
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 ul.	Gdynia
Poland	Synexus SCM Sp. z o.o. Oddzial	Katowice
Poland	Synexus Polska Sp. z o.o. Oddzial w Lodzi	Lódz	Lodz
Poland	Wojewódzki Specjalistyczny Szpital im. dr Wl. Bieganskiego w Lodzi	Lódz	Lodzkie
Poland	ID Clinic Arkadiusz Pisula	Myslowice	Slaskie
Poland	Synexus Polska Sp z o o Oddzial w Poznaniu	Poznan	Wielkopolska
Poland	Synexus Polska Sp. z o.o. Oddzial w Warszawie	Warsaw
Poland	Centrum Badan Klinicznych Piotr Napora Lekarze Spólka Partnerska	Wroclaw	Dolnoslaskie
Poland	EMC Instytut Medyczny	Wroclaw	Dolnoslaskie
Poland	Synexus Polska Sp. z o.o. Oddzial we Wroclawiu	Wroclaw	Wroclaw
Portugal	Unidade Local de Saúde do Alto Minho	Viana do Castelo
Portugal	Presa-Ramos	Vila Real	Lordelo
Puerto Rico	Clinical Research Puerto Rico	San Juan
Puerto Rico	Fundacion de Investigacion De Diego	San Juan
Romania	Institutul Regional de Gastroenterologie si Hepatologie Prof. Dr. O Fodor	Cluj-Napoca	Cluj
Russian Federation	Clinic Professor Gorbakova	Krasnogorsk	Moscow
Russian Federation	Moscow Regional Research and Clinical Institute M.F. Vladimirsky	Moscow
Russian Federation	Sklifosovsky Scientific Research Institution of Emergency Care	Moscow
Singapore	National University Hospital	Singapore
Spain	Complejo Hospitalario Torrecardenas	Almeria
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitari Vall d'Hebrón	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Ramón Y Cajal	Madrid
Spain	Hospital Clínico Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario Donostia	San Sebastian	Guipuzcoa
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Universitario Nuestra Senora de Valme	Sevilla
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Consorci Hospital General Universitari de València	Valencia
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Switzerland	Universitaetsspital Bern Inselspital	Bern
Switzerland	Kantonsspital St.Gallen Klinik für	St. Gallen	Saint Gallen
Taiwan	Chia-Yi Christian Hospital	Chiayi City	Chiayi
Taiwan	China Medical University Hospital	Taichung	Taichung City
Taiwan	Chang Gung Medical Foundation-LinKou Branch	Taoyuan
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham	England
United Kingdom	Synexus Hexham Clinical Research Centre	Hexham
United Kingdom	Hull and East Yorkshire Hospitals NHS Trust	Hull	England
United Kingdom	Synexus Lancashire Clinical Research Centre	Lancaster
United Kingdom	St James's University Hospital	Leeds	West Yorkshire
United Kingdom	Barts Health NHS Trust The Royal London Hospital	London
United Kingdom	Chelsea and Westminster Hospital NHS Foundation Trust	London	England
United Kingdom	Kings College Hospital NHS Foundation Trust	London	England
United Kingdom	Royal Free London NHS Foundation Trust	London	England
United Kingdom	Luton and Dunstable Hospital NHS Foundation Trust	Luton	England
United Kingdom	University Hospital of South Manchester NHS Foundation Trust	Manchester
United Kingdom	Newcastle Upon the Tyne Hospitals	Newcastle	England
United Kingdom	Nottingham Digestive Diseases Biomedical Research Unit	Nottingham	England
United Kingdom	Plymouth Hospitals NHS Trust	Plymouth	England
United Kingdom	Royal Stoke University Hospital	Stoke-on-Trent	England
United States	Texas Clinical Research Institute	Arlington	Texas
United States	Summit Clinical Research, LLC	Athens	Georgia
United States	Digestive Healthcare of Georgia - Atlanta	Atlanta	Georgia
United States	Piedmont Healthcare INC.	Atlanta	Georgia
United States	Innovative Medical Research of South Florida, Inc.	Aventura	Florida
United States	Franco Felizarta MD	Bakersfield	California
United States	Mercy Medical Center	Baltimore	Maryland
United States	Delta Research Partners, LLC	Bastrop	Louisiana
United States	Hassman Research Institute	Berlin	New Jersey
United States	Eastern Pennsylvania Gastroenterology and Liver Specialist	Bethlehem	Pennsylvania
United States	National Diabetes and Obesity Research Institute	Biloxi	Mississippi
United States	Summit Internal Medicine	Birmingham	Alabama
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Gastroenterology Associates of Fairfield County	Bridgeport	Connecticut
United States	Investigators Research Group, LLC	Brownsburg	Indiana
United States	Lahey Hospital & Medical Center	Burlington	Massachusetts
United States	Hope Clinical Research	Canoga Park	California
United States	Digestive Disease Associates	Catonsville	Maryland
United States	The Institute for Liver Health	Chandler	Arizona
United States	Investigational Drug Service, The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Mount Vernon Clinical Research	Chattanooga	Tennessee
United States	Clinical Research Professionals	Chesterfield	Missouri
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	eStudySite	Chula Vista	California
United States	GW Research	Chula Vista	California
United States	Consultants for Clinical Research	Cincinnati	Ohio
United States	Gastro Florida	Clearwater	Florida
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Iowa Digestive Disease Center	Clive	Iowa
United States	Peak Gastroenterology Associates	Colorado Springs	Colorado
United States	Gastro Center of Maryland	Columbia	Maryland
United States	The Ohio University - Gastroenterology, Hepatology	Columbus	Ohio
United States	Northeast GI Research Division	Concord	North Carolina
United States	Hi Tech and Global Research, LLC	Coral Gables	Florida
United States	Southern California Research Center	Coronado	California
United States	Citrus Valley Gastroenterology	Covina	California
United States	Avant Research Associates LLC	Crowley	Louisiana
United States	Cullman Clinical Trials	Cullman	Alabama
United States	Partners in Clinical Research	Cumberland	Rhode Island
United States	Top Medical Research, Inc	Cutler Bay	Florida
United States	Liver Center of Texas	Dallas	Texas
United States	Methodist Dallas Medical Center	Dallas	Texas
United States	Synexus	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	ICR Sites	Doral	Florida
United States	Digestive Health Specialists of the Southeast	Dothan	Alabama
United States	Physician's Research Options, LLC	Draper	Utah
United States	Duke University	Durham	North Carolina
United States	TriWest Research Associates	El Cajon	California
United States	South Denver Gastroenterology, PC	Englewood	Colorado
United States	Gastroenterology Associates of Northern Virginia	Fairfax	Virginia
United States	Inova Fairfax Medical Campus	Falls Church	Virginia
United States	Cumberland Research Associates, LLC	Fayetteville	North Carolina
United States	GastroIntestinal Associates	Flowood	Mississippi
United States	San Antonio Military Medical Center	Fort Sam Houston	Texas
United States	Baylor Scott & White All Saints Medical Center - Ft. Worth	Fort Worth	Texas
United States	Texas Digestive Disease Consultants - Fort Worth	Fort Worth	Texas
United States	Fresno Clinical Research Center (FCRC)	Fresno	California
United States	University of San Francisco, Fresno Medical Education Program	Fresno	California
United States	Digestive Health Associates of Texas-Rockwall	Garland	Texas
United States	Gastro One	Germantown	Tennessee
United States	Woodholme Gastroenterology Associates	Glen Burnie	Maryland
United States	Victory Clinical Research	Greenbelt	Maryland
United States	Carolina Research	Greenville	North Carolina
United States	Meritus Center for Clinical Research	Hagerstown	Maryland
United States	Digestive Health Research	Hermitage	Tennessee
United States	Qway Research, LLC	Hialeah	Florida
United States	Amir Ali Hassan, MD, PA	Houston	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	Biopharma Informatic, LLC	Houston	Texas
United States	Biopharma Informatic, LLC	Houston	Texas
United States	Centex Studies	Houston	Texas
United States	Liver Associates of Texas	Houston	Texas
United States	Michael E. DeBakey VA Medical Center (MEDVAMC)	Houston	Texas
United States	Pioneer Research Solutions, Inc.	Houston	Texas
United States	St. Luke's Medical Center	Houston	Texas
United States	Therapeutic Concepts, PA	Houston	Texas
United States	Marshall University Joan C. Edwards School of Medicine	Huntington	West Virginia
United States	National Research Institute	Huntington Park	California
United States	Indianapolis Gastroenterology Research Foundation	Indianapolis	Indiana
United States	Gastroenterology Associates - Crystal River	Inverness	Florida
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Mayo Clinic College of Medicine	Jacksonville	Florida
United States	East Tennessee Research Institute	Johnson City	Tennessee
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California San Diego	La Jolla	California
United States	eStudySite	La Mesa	California
United States	C-1 Headlands, Inc.	Lake Charles	Louisiana
United States	Meridien Research	Lakeland	Florida
United States	Florida Digestive Health Specialists	Lakewood Ranch	Florida
United States	Om Research	Lancaster	California
United States	Excel Clinical Research	Las Vegas	Nevada
United States	Jubilee Clinical Research, Inc.	Las Vegas	Nevada
United States	Machuca Family Medicine	Las Vegas	Nevada
United States	Sierra Clinical Research	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Digestive Health Research	Lebanon	Tennessee
United States	Arkansas Diagnostic Center	Little Rock	Arkansas
United States	Cedars-Sinai Medical Group	Los Angeles	California
United States	GastroIntestinal Biosciences	Los Angeles	California
United States	Global Research Institute	Los Angeles	California
United States	National Research Institute	Los Angeles	California
United States	Ruane Medical and Liver Health Institute	Los Angeles	California
United States	Southern California Kaiser Permanente, Los Angeles Medical Center	Los Angeles	California
United States	Gastroenterology Associates of Central Georgia	Macon	Georgia
United States	Objective GI D/B/A North Alabama GI Research Center	Madison	Alabama
United States	Meridien Research	Maitland	Florida
United States	Minnesota Gastroenterology, P.A.	Maplewood	Minnesota
United States	GI Specialists of Georgia - Marietta Office	Marietta	Georgia
United States	Tandem Clinical Research	Marrero	Louisiana
United States	Centex Studies, Inc.	McAllen	Texas
United States	UT-Memphis, Methodist University Hospital	Memphis	Tennessee
United States	Bruce W. Carter Department of Veterans Affairs Medical Center	Miami	Florida
United States	Clinical Pharmacology of Miami, LLC	Miami	Florida
United States	Genoma Research Group Inc.	Miami	Florida
United States	Medical Professional Clinical Research Center, INC	Miami	Florida
United States	Optimus U Corporation	Miami	Florida
United States	ProLive Medical Research	Miami	Florida
United States	Sanchez Clinical Research, Inc	Miami	Florida
United States	University of Miami Hospital	Miami	Florida
United States	San Marcus Research Clinic	Miami Lakes	Florida
United States	Intermountain Medical Center	Murray	Utah
United States	United Medical Doctors	Murrieta	California
United States	Vanderbilt University	Nashville	Tennessee
United States	Aquiant Research	New Albany	Indiana
United States	Yale University - New Haven	New Haven	Connecticut
United States	Nola Research Works, LLC	New Orleans	Louisiana
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Advanced Research Institute, Inc.	New Port Richey	Florida
United States	Beth Israel Medical Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	NYU Langone Health - Perlmutter Cancer Center	New York	New York
United States	Tandem Clinical Research	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Liver Institute of Virginia	Newport News	Virginia
United States	Digestive and Liver Disease Specialists	Norfolk	Virginia
United States	University Medical Group	North Providence	Rhode Island
United States	Digestive Disease Specialist, Inc.	Oklahoma City	Oklahoma
United States	Bioclinical Research Alliance	Orlando	Florida
United States	Omega Research Maitland, LLC	Orlando	Florida
United States	Palmtree Clinical Research Inc.	Palm Springs	California
United States	IMIC, Inc	Palmetto Bay	Florida
United States	Innovation Medical Research Center	Palmetto Bay	Florida
United States	National Research Institute	Panorama City	California
United States	Pasadena Liver Center	Pasadena	California
United States	LinQ Research, LLC	Pearland	Texas
United States	Gastroenterology Associates of Pensacola	Pensacola	Florida
United States	UPMC -Center for Liver Diseases	Pittsburgh	Pennsylvania
United States	VA Pittsburgh Healthcare System	Pittsburgh	Pennsylvania
United States	Advanced Medical Research	Port Orange	Florida
United States	Care Access Research, Pottsville	Pottsville	Pennsylvania
United States	Alliance Clinical Research LLC	Poway	California
United States	Wake Research Associates	Raleigh	North Carolina
United States	Rapid City Medical Center	Rapid City	South Dakota
United States	Amici Clinical Research	Raritan	New Jersey
United States	Stanford School of Medicine, Center for Clinical Sciences Research	Redwood City	California
United States	Inland Empire Liver Foundation	Rialto	California
United States	McGuire Veterans Affairs Medical Center	Richmond	Virginia
United States	VCU Medical Center	Richmond	Virginia
United States	Advanced Clinical Research - Center for Digestive Health	Riverton	Utah
United States	Gastroenterology Consultants of Southwest Virginia Research	Roanoke	Virginia
United States	Saint Louis University	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	American Research Corporation	San Antonio	Texas
United States	Anson Medicine	San Antonio	Texas
United States	Clinical Trials of Texas Inc	San Antonio	Texas
United States	Diabetes & Glandular Disease Clinic, P.A. (DGD)	San Antonio	Texas
United States	Endeavor Clinical Trials, LLC	San Antonio	Texas
United States	Quality Research Inc.	San Antonio	Texas
United States	Southern Star Research Institute, LLC SAGACT PLLC.	San Antonio	Texas
United States	Precision Research Institute	San Diego	California
United States	Southern California Permanente Medical Group	San Diego	California
United States	UCSF School of Medicine	San Francisco	California
United States	Harborview Medical Center	Seattle	Washington
United States	Liver Institute Northwest	Seattle	Washington
United States	Swedish Medical Center	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Louisiana Research Center	Shreveport	Louisiana
United States	Digestive Research Alliance of Michiana	South Bend	Indiana
United States	Mount Olympus Medical Research, LLC	Sugar Land	Texas
United States	Guardian Angel Research Center	Tampa	Florida
United States	Tampa General Hospital	Tampa	Florida
United States	Bioclinica Research	The Villages	Florida
United States	Kansas Medical Clinic-Gastroenterology	Topeka	Kansas
United States	Adobe Gastroenterology Research, LLC	Tucson	Arizona
United States	Del Sol Research Management LLC	Tucson	Arizona
United States	Del Sol Research Management, LLC	Tucson	Arizona
United States	Options Health Research	Tulsa	Oklahoma
United States	Upland Clinical Research	Upland	California
United States	Island View GI	Ventura	California
United States	Care Access Research-Warwick	Warwick	Rhode Island
United States	Texas Digestive Disease Consultants	Webster	Texas
United States	Clinical Trials of America LLC	West Monroe	Louisiana
United States	Western States Clinical Research, Inc.	Wheat Ridge	Colorado
United States	PMG Research of Winston-Salem	Winston-Salem	North Carolina
United States	Umass Memorial Medical Center	Worcester	Massachusetts
United States	Digestive Disease Associates, LTD	Wyomissing	Pennsylvania
United States	Florida Medical Clinic	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Tobira Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Israel,  Italy,  Latvia,  Mexico,  New Zealand,  Norway,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Singapore,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage and No Worsening of Steatohepatitis on Liver Histology at Month 12	Fibrosis stage was evaluated using the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or 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 a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.	Month 12
Primary	Time to First Occurrence of Adjudicated Events in the Full Study Cohort	Time to first occurrence from Baseline was defined as the number of days from the first dose of randomized investigational product to the onset of the first occurrence of any of the following adjudicated events: death (all cause), histopathologic progression to cirrhosis, liver transplant, model for end stage liver disease (MELD) score =15, ascites, hospitalization for onset of: variceal bleed, hepatic encephalopathy, spontaneous bacterial peritonitis. MELD is a scoring system for assessing the severity of chronic liver disease and 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.	From first dose of study drug to onset of first occurrence of the event (Up to approximately 42 months)
Secondary	Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages and No Worsening of Steatohepatitis on Liver Histology at Month 12	Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or 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 NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.	Month 12
Secondary	Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis at Month 12	Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.	Month 12
Secondary	Part 1: Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis at Month 12	Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.	Month 12
Secondary	Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage and No Worsening of Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort	Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or 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 NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.	Month 12
Secondary	Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort	Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.	Month 12
Secondary	Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages and No Worsening of Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort	Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or 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 NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.	Month 12
Secondary	Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 12 in the Full Study Cohort	Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.	Month 12
Secondary	Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage and No Worsening of Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort	Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or 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 NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.	Month 60
Secondary	Percentage of Participants With Improvement in Fibrosis by at Least 1 Stage Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort	Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages 0=none, 1=perisinusoidal or periportal, 1A=mild, zone 3, perisinusoidal, 1B=moderate, zone 3, perisinusoidal, 1C=portal/periportal, 2=perisinusoidal and portal/periportal, 3=bridging fibrosis, 4=cirrhosis.	Month 60
Secondary	Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages and No Worsening of Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort	Fibrosis stage was evaluated using the NASH CRN Fibrosis Staging System with stages: 0=none; 1=perisinusoidal or 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 NAS categories. NAS is a semiquantitative scoring system based on the unweighted sum of: steatosis (0=<5% to 3=>66%), lobular inflammation (0=no foci to 3=>4 foci/200x), and hepatocellular ballooning (0=none to 2=many cells/prominent ballooning) scores. Improvement in fibrosis is a decrease in the NASH CRN fibrosis stage.	Month 60
Secondary	Percentage of Participants With Improvement in Fibrosis by at Least 2 Stages Regardless of Effect on Steatohepatitis on Liver Biopsy at Month 60 in the Full Study Cohort	Fibrosis stage was evaluated using NASH CRN Fibrosis Staging System with stages 0=None, 1=Perisinusoidal or periportal, 1A=Mild, zone 3, perisinusoidal, 1B=Moderate, zone 3, perisinusoidal, 1C=Portal/periportal, 2=Perisinusoidal and portal/periportal, 3=Bridging fibrosis, 4=Cirrhosis.	Month 60