Phase 3 Study to Evaluate the Efficacy and Safety of Elafibranor Versus Placebo in Patients With Nonalcoholic Steatohepatitis (NASH)

Nonalcoholic Steatohepatitis (NASH) With Fibrosis Clinical Trial

— RESOLVE-IT  

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Study to Evaluate the Efficacy and Safety of Elafibranor in Patients With Nonalcoholic Steatohepatitis (NASH) and Fibrosis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02704403
• Other study ID #: GFT505-315-1
• Secondary ID: 2015-005385-38
• Status: Terminated
• Phase: Phase 3
• Start date: March 2016
• Est. completion date: October 28, 2020

Study information

• Verified date: February 2022
• Source: Genfit
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objectives of this study are to evaluate the effect of Elafibranor treatment compared to placebo on 1) histological improvement and 2) all-cause mortality and liver-related outcomes in patients with nonalcoholic steatohepatitis (NASH) and fibrosis.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2157
• Est. completion date: October 28, 2020
• Est. primary completion date: October 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Males or females aged from 18 to 75 years inclusive at first screening visit.

2. Must provide signed written informed consent and agree to comply with the study protocol.

3. Females participating in this study must be of nonchildbearing potential or using highly efficient contraception for the full duration of the study and for 1 month after the end of treatment, as described below:

1. Cessation of menses for at least 12 months due to ovarian failure,

2. Surgical sterilization such as bilateral oopherectomy, hysterectomy, or medically documented ovarian failure

3. If requested by local IRB regulations and/or National laws, sexual abstinence may be considered adequate (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)

4. Using a highly effective nonhormonal method of contraception (bilateral tubal occlusion, vasectomized partner, or intra-uterine device)

5. Double contraception with barrier AND highly effective hormonal method of contraception (oral, intravaginal, or transdermal combined estrogen and progestogen hormonal contraception associated with inhibition of ovulation; oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation; or intrauterine hormone-releasing system). The hormonal contraception must be started at least 1 month prior to Randomization.

4. Histological confirmation of steatohepatitis on a diagnostic liver biopsy by central reading of the slides (biopsy obtained within 6 months prior to randomization or during the screening period) with at least 1 in each component of the NAS score (steatosis scored 0-3, ballooning degeneration scored 0-2, and lobular inflammation scored 0-3).

5. NAS score =4.

6. Fibrosis stage of 1 or greater and below 4, according to the NASH CRN fibrosis staging system.

7. Stable dose of vitamin E, polyunsaturated fatty acids, or ursodeoxycholic acid from at least 6 months prior to diagnostic liver biopsy

8. For participants with type 2 diabetes, glycemia must be controlled. If glycemia is controlled by antidiabetic drugs, change in anti-diabetic therapy must follow these requirements:

1. No qualitative change 6 months prior to diagnostic liver biopsy up to Randomization (i.e., implementation of a new anti-diabetic therapy) for participants treated with metformin, gliptins, sulfonylureas, sodium/glucose cotransporter (SGLT) 2 inhibitors, glucagon-like peptide (GLP)-1 agonists, or insulin. Dose changes of these medications are allowed in the 6 months prior to diagnostic liver biopsy, except for GLP-1 agonists, which must remain on stable dose in the 6 months prior to diagnostic liver biopsy.

2. No implementation of GLP-1 agonists and SGLT2 inhibitors up to 72 weeks of treatment (Visit 7).

Initiation of any other antidiabetic drugs is allowed after Randomization based on treating physicians' judgment, except for glitazones which are prohibited 6 months prior to diagnostic liver biopsy until the end of treatment.

Exclusion Criteria:

1. Known heart failure (Grade I to IV of New York Heart Association classification).

2. History of efficient bariatric surgery within 5 years prior to screening.

3. Uncontrolled hypertension during the Screening Period despite optimal antihypertensive therapy

4. Type 1 diabetes participants .

5. Participants with decompensated diabetes (HbA1c>9%).

6. Participants with a history of clinically significant acute cardiac event within 6 months prior to screening

7. Weight loss of more than 5% within 6 months prior to randomization

8. Compensated and decompensated cirrhosis

9. Current or recent history (<5 years) of significant alcohol consumption

10. Pregnant or lactating females or females planning to become pregnant during the study period.

11. Other well documented causes of chronic liver disease according to standard diagnostic procedures

12. Participants with previous exposure to Elafibranor

13. Prohibited concomitant medication

14. Any medical conditions that may diminish life expectancy to less than 2 years including known cancers.

15. Evidence of any other unstable or untreated clinically significant immunological, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric disease.

16. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.

17. Participants with biological criteria exclusion as per effective protocol

Related Conditions & MeSH terms

• Fatty Liver
• Fibrosis
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis (NASH) With Fibrosis

Intervention

Drug:
• Elafibranor

• Placebo

Locations

Country	Name	City	State
Argentina	CCBR Clinical Research	Buenos Aires
Argentina	Centro de Investigación y Prevención Cardiovascular SA (CIPREC)	Buenos Aires
Argentina	Fundación Sanatorio Güemes	Buenos Aires
Argentina	Hospital Alemán	Buenos Aires
Argentina	Hospital Británico de Buenos Aires	Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires
Argentina	Axismed S.R.L	Caba	Buenos Aires
Argentina	Sanatorio Güemes	Caba	Buenos Aires
Argentina	Centro De Hepatologia Ciudad de La Plata	La Plata
Argentina	Hospital Universitario Austral	Pilar
Argentina	Dim Clinica Privada	Ramos Mejía
Argentina	Hospital Provincial del Centenario	Rosario
Argentina	Instituto Medico Alas	Salta
Argentina	Instituto de Investigaciones Clinicas San Nicolas SRL	San Nicolas	Buenos Aires
Australia	Flinders Medical Centre	Bedford Park
Australia	Box Hill Hospital	Box Hill
Australia	Monash Medical Centre Clayton	Clayton
Australia	Concord Repatriation General Hospital	Concord
Australia	St. Vincent's Hospital Melbourne	Fitzroy
Australia	Austin Hospital	Heidelberg
Australia	Nepean Hospital	Kingswood
Australia	The St George Hospital	Kogarah
Australia	The Alfred Hospital	Melbourne
Australia	Fiona Stanley Hospital	Murdoch
Australia	Sir Charles Gairdner Hospital (SCGH)	Nedlands
Australia	Westmead Hospital	Westmead
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Hôpital Erasme	Bruxelles
Belgium	Universitair Ziekenhuis Brussel	Bruxelles
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Universitair Ziekenhuis Leuven	Leuven
Belgium	Centre Hospitalier de Wallonie Picardie (CHWAPI)	Tournai
Canada	University of Calgary, Cumming School of Medicine	Calgary, AB
Canada	Monteregie Centre de Recherche	Greenfield Park	Quebec
Canada	Queen Elizabeth II Health Sciences Centre, Nova Scotia Health Authority	Halifax
Canada	Mc Gill University Health Centre (MUHC)	Montreal
Canada	The Montreal Chest Institute	Montréal	Quebec
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Toronto Liver Centre	Toronto	Ontario
Canada	Toronto Western Hospital	Toronto	Ontario
Canada	LAIR Centre	Vancouver	British Columbia
Canada	Vancouver General Hospital (VGH) - Gordon and Leslie Diamond Health Care Centre	Vancouver	British Columbia
Canada	University of Manitoba	Winnipeg, MB
Chile	Hospital de La Serena	La Serena
Chile	Alta Salud	Los Ángeles
Chile	Centro de Estudios Clinicos Barros Luco SPA (Patients seen, Fibroscan stored and Drug Shipment)	Santiago
Chile	Hospital Clínico UC	Santiago
Chile	Hospital Clínico Universidad de Chile	Santiago
Chile	Clínica Reñaca	Vina Del Mar
Colombia	Fundación Cardio Infantil - Instituto de Cardiología	Bogotá
Colombia	Solano&Terront Servicios Médicos LTDA - Unidad Integral de Endocrinologia UNIENDO	Bogotá	Bogota D.C
Colombia	Centro Medico Imbanaco	Cali
Colombia	Fundación Valle del Lili	Cali
Colombia	Hospital Pablo Tobon Uribe	Medellin
Colombia	Hospital Universitario San Vicente de Paul Fundación	Medellin
Colombia	Fundacion Hospitalaria San Vicente de Paul	Medellín
Czechia	Fakultní Nemocnice Brno	Brno
Czechia	Research Site S.R.O.	Plzen
Czechia	Research Site, s.r.o	Plzen
Czechia	KlinMed s.r.o.	Praha 2
Denmark	Aarhus University Hospital	Aarhus
Finland	Helsinki University Central Hospital	Helsinki
France	CHU Amiens Picardie	Amiens
France	CHU Angers	Angers
France	Hôpital Antoine-Béclère	Clamart
France	Hôpital Beaujon	Clichy
France	Hôpital Henri Mondor	Créteil
France	CHU Limoges - Hôpital Dupuytren	Limoges
France	Hôpital de la Croix-Rousse	Lyon
France	Hôpital Saint Joseph	Marseille
France	CHRU Montpellier- Hôpital Saint Eloi	Montpellier
France	CHU de Nantes - Hôpital Laennec	Nantes
France	CHU de Nice- Hôpital de l'Archet II	Nice
France	Hôpital Cochin	Paris
France	Hopital Pitie-Salpetriere	Paris
France	Hôpital Saint-Antoine	Paris
France	Hôpital Haut-Lévêque	Pessac
France	CHU Toulouse - Hôpital Purpan	Toulouse
France	CHU Nancy - Hôpital Brabois	Vandoeuvre Les Nancy
France	Hôpital Paul Brousse	Villejuif
Germany	Universitätsklinikum RWTH Aachen	Aachen
Germany	Gastroenterologie am Bayerischen Platz/ Gastro-Studien	Berlin
Germany	Liver Center	Berlin
Germany	Universitätsklinikum Bonn	Bonn
Germany	Universitätsklinikum Essen	Essen
Germany	Universitätsklinikum Frankfurt - Goethe Universität	Frankfurt
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	Asklepios Klinik St. Georg	Hamburg
Germany	Universitätsklinikum Hamburg-Eppendorf (UKE)	Hamburg
Germany	Medizinische Hochschule Hannover (MHH)	Hannover
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Köln	Köln
Germany	Universitätsklinikum Köln	Köln	Northwest
Germany	EUGASTRO GmbH	Leipzig
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Universitätsklinikum Magdeburg	Magdeburg
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Universitätsklinikum Würzburg	Würzburg
Italy	Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi	Bologna
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"	Napoli
Italy	Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Italy	Policlinico Tor Vergata	Roma
Italy	Ospedale Casa Sollievo della Sofferenza I.R.C.C.S.	San Giovanni Rotondo
Italy	Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino - Ospedale Molinette	Torino
Mexico	Centro de Investigación Clínica del Pacífico, S.A de C.V.	Acapulco
Mexico	Hospital Maria Auxiliadora	Guadalajara
Mexico	Hospital Angeles Clinica Londres	Mexico	DIF
Mexico	Consultorio Medico	Mexico City
Mexico	Médica Sur	Mexico City
Mexico	Accelerium S de RL de C.V.	Monterrey
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Vrije Universiteit Medical Center	Amsterdam
Netherlands	Maastricht UMC+	Maastricht
Netherlands	Radboud UMC	Nijmegen
Portugal	Centro Hospitalar e Universitário de Coimbra, EPE - Hospitais da Universidade de Coimbra	Coimbra
Portugal	Centro Hospitalar de Lisboa Norte, EPE - Hospital Santa Maria	Lisboa
Portugal	Centro Hospitalar Lisboa Central, EPE - Hospital Santo António dos Capuchos	Lisboa
Portugal	Centro Hospitalar de São João	Porto
Portugal	Centro Hospitalar de São João, EPE - Hospital de São João	Porto
Portugal	Centro Hospita de Tras-os-Montes e Alto Douro, EPE	Vila Real
Puerto Rico	Caparra Internal Medicine Research Center	Rio Grande
Puerto Rico	Fundación de Investigación	San Juan
Puerto Rico	Fundacion de Investigacion de Diego	San Juan
Puerto Rico	Klinical Investigations Group, LLC	San Juan
Romania	Institutul Clinic Fundeni	Bucharest
Romania	Institutul National de Boli Infectioase "Prof. Dr. Matei Bals"	Bucharest
Romania	SC Cabinet Particular Policlinic Algomed SRL	Timisoara
Romania	Spitalul Clinic Judetean de Urgenta "Pius Brinzeu" Timisoara	Timisoara
Russian Federation	FSBRI "Federal Research Center of nutrition and biotechnology	Moscow
Russian Federation	I. M. Sechenov - First Moscow State Medical University	Moscow
Russian Federation	M. F. Vladimirsky - Clinical Research Institution of Moscow Region	Moscow
Russian Federation	Military medical academy n. a. S.M. Kirov	Saint Petersburg
Russian Federation	St Petersburg State Budgetary Healthcare Institution City Clinical Hospital N°31	Saint Petersburg
Russian Federation	City Clinical Hospital No. 31	St. Petersburg
South Africa	Mediclinic Constantiaberg	Cape Town
South Africa	Tiervlei Trial Centre	Cape Town
South Africa	Phoenix Pharma (Pty) Ltd	Port Elizabeth
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Puerta de Hierro	Majadahonda
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Complexo Hospitalario Universitario de Pontevedra	Pontevedra
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Campus Hospital Universitario Virgen del Rocío - Instituto de Biomedicina de Sevilla (IBIS)	Sevilla
Sweden	Karolinska Universitetssjukhuset Huddinge	Stockholm
Switzerland	INSELSPITAL, University Hospital Bern	Bern
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne
Switzerland	Kantonsspital St. Gallen	Saint Gallen
Switzerland	UniversitätsSpital Zürich	Zurich
Turkey	Ankara Üniversitesi Tip Fakültesi	Ankara
Turkey	Istanbul Universitesi Istanbul Tip Fakultesi	Çapa
Turkey	Bezmiâlem Vakif Üniversitesi	Fatih
Turkey	Saglik Bilimleri Üniversitesi Ümraniye Egitim ve Arastirma Hastanesi	Istanbul
Turkey	Ege Üniversitesi	Izmir
Turkey	Marmara Üniversitesi Egitim ve Arastirma Hastanesi	Pendik
United Kingdom	University Hospitals Birmingham NHS foundation Trust	Birmingham
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Frimley Park Hospital NHS Foundation Trust	Frimley
United Kingdom	Hull and East Yorkshire Hospitals NHS Trust - Hull Royal Infirmary	Hull
United Kingdom	Bart Health NHS Trust- Royal London Hospital	London
United Kingdom	Guy's and St Thomas' NHS Foundation Trust - St Thomas' Hospital	London
United Kingdom	St George's University Hospitals NHS Foundation Trust - St George's Hospital	London
United Kingdom	The Royal Free London NHS Foundation Trust - The Royal Free Hospital	London
United Kingdom	The Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital	Newcastle upon Tyne
United Kingdom	Nottingham University Hospitals NHS FoundationTrust - Queen's Medical Centre	Nottingham
United Kingdom	Plymouth Hospitals NHS Trust - Derriford Hospital	Plymouth
United Kingdom	Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital	Portsmouth
United States	Southwest Gastroenterology Associates	Albuquerque	New Mexico
United States	Texas Clinical Research Institute	Arlington	Texas
United States	Asheville Gastroenterology Associates	Asheville	North Carolina
United States	Summit Clinical Research	Athens	Georgia
United States	Atlanta Medical Center, Inc.	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Piedmont Atlanta Hospital	Atlanta	Georgia
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Excel Medical Clinical Trials LLC	Boca Raton	Florida
United States	Beth Israel Deaconess Medical Center (BIDMC)	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	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	The Institute for Liver Health	Chandler	Arizona
United States	UNC Health Care System	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	Ralph H. Johnson VA Medical Center	Charleston	South Carolina
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Northwestern Memorial Hospital - Arkes Family Pavilion	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	GW Research, Inc.	Chula Vista	California
United States	Consultants for Clinical Research	Cincinnati	Ohio
United States	Ohio Gastroenterology & Liver Institute	Cincinnati	Ohio
United States	University of Cincinnati Physicians Company , LLC	Cincinnati	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Southern California Research Center	Coronado	California
United States	Liver Center of Texas	Dallas	Texas
United States	Methodist Dallas Medical Center	Dallas	Texas
United States	Henry Ford Health System, Division of Gastroenterology & Hepatology	Detroit	Michigan
United States	Integrity Clinical Research LLC	Doral	Florida
United States	Digestive Health Specialists of the Southeast	Dothan	Alabama
United States	Duke Gastroenterology	Durham	North Carolina
United States	South Denver Gastroenterology	Englewood	Colorado
United States	Inova Fairfax Medical Campus - Center for Liver Disease	Falls Church	Virginia
United States	Cumberland Research Associates, LLC	Fayetteville	North Carolina
United States	Gastrointestinal Associates & Endoscopy Center	Flowood	Mississippi
United States	Baylor All Saints Medical Center - Baylor Research Institute	Fort Worth	Texas
United States	Fresno Clinical Research Center	Fresno	California
United States	University of California, San Francisco, Fresno Community Regional Medical Center	Fresno	California
United States	University of California, San Francisco, Fresno Community Regional Medical Center	Fresno	California
United States	University of Florida	Gainesville	Florida
United States	DHAT Research Institute	Garland	Texas
United States	The Institute for Liver Health	Glendale	Arizona
United States	Gastroenterology Associates of Hazard	Hazard	Kentucky
United States	Associates in Gastroenterology, PLC	Hermitage	Tennessee
United States	The Queen's Medical Center	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	Brooke Army Medical Center	Houston	Texas
United States	Centex Studies Inc.	Houston	Texas
United States	Gulf Coast Research Group LLC	Houston	Texas
United States	Liver Associates of Texas, P.A.	Houston	Texas
United States	Research Specialists of Texas	Houston	Texas
United States	Carolinas Center for Liver Disease, Carolinas HealthCare System/Atrium Health	Huntersville	North Carolina
United States	Nature Coast Clinical Research	Inverness	Florida
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Mayo Clinic Hospital	Jacksonville	Florida
United States	Kansas City Research Institute	Kansas City	Missouri
United States	Kansas City VA Medical Center	Kansas City	Missouri
United States	St. Luke's Liver Transplant & Specialist	Kansas City	Missouri
United States	Scripps Clinic Torrey Pines	La Jolla	California
United States	University of California - San Diego	La Jolla	California
United States	Atlantic Gastroenterology Associates, LLC	Lakewood Ranch	Florida
United States	Florida Digestive Health Specialists, LLP	Lakewood Ranch	Florida
United States	University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Liver Wellness Center	Little Rock	Arkansas
United States	Gastroenterology Consultants of San Antonio	Live Oak	Texas
United States	Loma Linda University Medical Center - Transplantation Insitute	Loma Linda	California
United States	VA Long Beach Healthcare System	Long Beach	California
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Gastrointestinal Biosciences Clinical Trials LLC	Los Angeles	California
United States	Keck Hospital of USC	Los Angeles	California
United States	Ruane Clinical Research Group Inc.	Los Angeles	California
United States	Veterans Affaires Greater Los Angeles Healthcare System, West LA VA Medical Center	Los Angeles	California
United States	Veterans Affairs Greater Los Angeles Healthcare System	Los Angeles	California
United States	University of Louisville Medical / Dental Complex	Louisville	Kentucky
United States	Hofstra Northwell School of Medicine	Manhasset	New York
United States	Gastrointestinal Specialists of Georgia, PC	Marietta	Georgia
United States	Loyola University Chicago	Maywood	Illinois
United States	Centex Studies Inc	McAllen	Texas
United States	Methodist University Hospital	Memphis	Tennessee
United States	Miami VA Healthcare System	Miami	Florida
United States	University of Miami - Miller School of Medicine	Miami	Florida
United States	University of Miami - Schiff Center for Liver Diseases	Miami	Florida
United States	Diabetes & Endocrinology Consultants	Morehead City	North Carolina
United States	Quality Medical Research, PLLC	Nashville	Tennessee
United States	Rutgers, Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Yale University School of Medicine, Section of Digestive Diseases	New Haven	Connecticut
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Beth Israel Medical Center	New York	New York
United States	Concorde Medical Group	New York	New York
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	New York-Presbyterian Hospital - Columbia University Medical Center	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	Rutgers, New Jersey Medical School	Newark	New Jersey
United States	Bon Secours Liver Institute of Virginia - Newport News	Newport News	Virginia
United States	Alliance Clinical Research	Oceanside	California
United States	National Research Institute	Panorama City	California
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	Drexel University, College of Medicine	Philadelphia	Pennsylvania
United States	Temple University Health System	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Banner University Medical Center Phoenix	Phoenix	Arizona
United States	Dignity Health St. Joseph's Hospital	Phoenix	Arizona
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	UPMC Montefiore	Pittsburgh	Pennsylvania
United States	Premier Medical Group	Poughkeepsie	New York
United States	Alliance Clinical Research	Poway	California
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Wake Research Associates	Raleigh	North Carolina
United States	Bon Secours Liver Institute of Virginia - Richmond	Richmond	Virginia
United States	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Kaiser Permanente Shady Grove Medical Center	Rockville	Maryland
United States	Pinnacle Clinical Research, PLLC	Rollingwood	Texas
United States	University of California, Davis Medical Center	Sacramento	California
United States	Saint Louis University School of Medicine	Saint Louis	Missouri
United States	University of Utah School of Medicine	Salt Lake City	Utah
United States	Pinnacle Clinical Research, PLLC	San Antonio	Texas
United States	The Texas Liver Institute, Inc.	San Antonio	Texas
United States	Medical Associates Research Group, Inc.	San Diego	California
United States	University of California, San Diego Airway Research and Clinical Trials Center	San Diego	California
United States	VA San Diego HealthCare System	San Diego	California
United States	Quest Clinical Research	San Francisco	California
United States	Sutter West Bay Hospitals dba California Pacific Medical Center	San Francisco	California
United States	University of California, San Francisco, Medical Center at Parnassus	San Francisco	California
United States	Harborview Medical Center	Seattle	Washington
United States	Swedish Organ Transplant and Liver Center	Seattle	Washington
United States	Louisiana Research Center, LLC	Shreveport	Louisiana
United States	Texas Digestive Consultants (TDDC)	Southlake	Texas
United States	Kaiser Permanente Springfield Medical Center	Springfield	Virginia
United States	Piedmont Healthcare	Statesville	North Carolina
United States	Adobe Clinical Research, LLC	Tucson	Arizona
United States	Institute for Liver Health	Tucson	Arizona
United States	The University of Arizona College of Medicine Liver Research Institute	Tucson	Arizona
United States	Options Health Research, LLC	Tulsa	Oklahoma
United States	Ventura Clinical Trials	Ventura	California
United States	Victoria Gastroenterology	Victoria	Texas
United States	Georgetown University Hospitals	Washington	District of Columbia
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	South Florida Center of Gastroenterology, PA	Wellington	Florida
United States	Trial Management Associates	Wilmington	North Carolina
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts
United States	Florida Medical Clinic, PA	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Genfit

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  Chile,  Colombia,  Czechia,  Denmark,  Finland,  France,  Germany,  Italy,  Mexico,  Netherlands,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  South Africa,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Elafibranor-treated Participants Relative to Placebo Achieving Resolution of Nonalcoholic Steatohepatitis Without Worsening of Fibrosis	To evaluate the effect of Elafibranor compared to placebo on liver histology in nonalcoholic steatohepatitis (NASH) participants with fibrosis by assessing the following endpoint: The number of Elafibranor-treated participants relative to placebo achieving NASH resolution without worsening of fibrosis. This outcome measure is for the surrogate endpoint analysis.	Measurement at 72 weeks
Primary	Time to Long-term Outcome Composed of All-cause Mortality, Cirrhosis, and Liver-related Clinical Outcomes	Composite long-term outcome measured by the number of participants with the onset of any of the adjudicated events, composed of death due to any cause, histological liver cirrhosis, and the full list of portal hypertension/cirrhosis related events as follows: liver transplantation; model for end stage liver disease (MELD) score greater than or equal to 15 for participants with baseline score less than or equal to 12, and onset of variceal bleeding requiring hospitalization, hepatic encephalopathy with West Haven/Conn score greater than or equal to 2 and requiring hospitalization, spontaneous bacterial peritonitis, and ascites requiring treatment. The MELD scale ranges from 6 to 40, showing how much a participant needs a liver transplant: higher number is more urgent. The West Haven/Conn scale is 5-point (0 to 4) grading severity of hepatic encephalopathy: higher score means worse hepatic encephalopathy. This outcome measure is for the long-term endpoint analysis.	From first randomization up to early termination of the study corresponding to 54 months (54 months being the longest duration for any given participant)
Secondary	Number of Elafibranor-treated Participants Relative to Placebo Achieving Improvement of Fibrosis of at Least 1 Stage	To evaluate the effect of Elafibranor compared to placebo on liver histology in nonalcoholic steatohepatitis (NASH) participants by assessing the following endpoint: The number of Elafibranor-treated participants relative to placebo achieving improvement of liver fibrosis of at least 1 stage according to NASH Clinical Research Network (CRN) Scoring. As the primary efficacy objective was not met, the secondary efficacy endpoints were not formally tested. This outcome measure is for the surrogate endpoint analysis.	Measurements at 72 weeks
Secondary	Change From Baseline of Hemoglobin A1c (HbA1c) in Diabetic Participants After 72 Weeks of Treatment in Elafibranor-treated Participants Relative to Placebo	Hemoglobin A1c (HbA1c) were tested at Week 72. Changes from baseline in HbA1c at Week 72 were evaluated. As the primary efficacy objective was not met, the secondary efficacy endpoints were not formally tested. This outcome measure is for the surrogate endpoint analysis.	Measurements after 72 weeks of treatment and up to study termination
Secondary	Change From Baseline of High-density Lipoprotein (HDL) Cholesterol After 72 Weeks of Treatment in Elafibranor-treated Participants Relative to Placebo	High-density lipoprotein (HDL) cholesterol was tested at Week 72. Changes from baseline in HDL cholesterol were evaluated at Week 72. As the primary efficacy objective was not met, the secondary efficacy endpoints were not formally tested. This outcome measure is for the surrogate endpoint analysis.	Measurements after 72 weeks of treatment and up to study termination
Secondary	Change From Baseline of Low-density Lipoprotein (LDL) Cholesterol After 72 Weeks of Treatment in Elafibranor-treated Participants Relative to Placebo	Low-density lipoprotein (LDL) cholesterol was tested at Week 72. Changes from baseline in LDL cholesterol were evaluated at Week 72. As the primary efficacy objective was not met, the secondary efficacy endpoints were not formally tested. This outcome measure is for the surrogate endpoint analysis.	Measurements after 72 weeks of treatment and up to study termination
Secondary	Change From Baseline of Homeostatic Model Assessment-IR (HOMA-IR) After 72 Weeks of Treatment in Elafibranor-treated Participants Relative to Placebo in Non-diabetic Participants	Homeostatic model assessment-IR (HOMA-IR) was tested at Week 72. Changes from baseline in HOMA-IR were evaluated at Week 72. As the primary efficacy objective was not met, the secondary efficacy endpoints were not formally tested. This outcome measure is for the surrogate endpoint analysis.	Measurements after 72 weeks of treatment and up to study termination
Secondary	Change From Baseline of Non-high Density Lipoprotein Cholesterol After 72 Weeks of Treatment in Elafibranor-treated Participants Relative to Placebo	Non-high density lipoprotein (HDL) cholesterol was tested at Week 72. Changes from baseline in non-HDL cholesterol were evaluated at Week 72. As the primary efficacy objective was not met, the secondary efficacy endpoints were not formally tested. This outcome measure is for the surrogate endpoint analysis.	Measurements after 72 weeks of treatment and up to study termination
Secondary	Change From Baseline of Triglycerides After 72 Weeks of Treatment in Elafibranor-treated Participants Relative to Placebo	Triglycerides was tested at Week 72. Changes from baseline in triglycerides were evaluated at Week 72. As the primary efficacy objective was not met, the secondary efficacy endpoints were not formally tested. This outcome measure is for the surrogate endpoint analysis.	Measurements after 72 weeks of treatment and up to study termination