A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 )

NASH - Nonalcoholic Steatohepatitis Clinical Trial

— NATiV3  

Official title:

A Randomised, Double-blind, Placebo-controlled, Multicentre, Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) and Fibrosis Stages F2 and F3

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04849728
• Other study ID #: 337HNAS20011
• Status: Recruiting
• Phase: Phase 3
• Start date: August 19, 2021
• Est. completion date: September 30, 2026

Study information

• Verified date: January 2024
• Source: Inventiva Pharma
• Contact: Pascaline Clerc
• Phone: 2024998937/0644637545
• Email: clinical.contact[@]inventivapharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis histological stage F2 or F3

Description:

Primary objectives

This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis stage F2 or F3 and consists of 2 sequential parts - an initial double-blind placebo-controlled (DBPC) period (Part A) followed by a double-blind active treatment extension (ATE) period (Part B), with the following primary objectives:

Part A To assess the safety and efficacy of lanifibranor compared to placebo on 'NASH resolution and improvement of fibrosis' assessed by liver histology.

Part B To assess the safety of lanifibranor beyond the DBPC period. Secondary objectives

Key secondary objectives of Part 1:

• To assess the effect of lanifibranor compared to placebo on NASH resolution and no worsening of fibrosis

• To assess the effect of lanifibranor compared to placebo on improvement of fibrosis with no worsening of NASH

Other secondary objectives of both Part 1 and Part 2:

• To assess the effect of lanifibranor on other key histological features of NASH (only for DBPC period)

• To assess the effect of lanifibranor on NASH resolution and improvement of fibrosis in diabetic patients (only for DBPC period)

• To assess the effect of lanifibranor on liver tests

• To assess the effect of lanifibranor on glycaemic parameters

• To assess the effect of lanifibranor on lipid parameters

• To assess the effect of lanifibranor on liver stiffness and steatosis assessed by elastography.

• To assess the effect of lanifibranor on health-related quality of life

• To assess the safety of lanifibranor

• To assess population PK modeling through plasma levels of lanifibranor using sparse sampling scheme (only for DBPC period)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: September 30, 2026
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Prescreening Criteria:

• Diagnosed with NASH on prior liver biopsy

• Type 2 diabetes with high waist circumference or obesity or hepatic steatosis on ultrasound

• At least 3 of the components of metabolic syndrome

Inclusion Criteria:

1. Male or female, aged =18 years at the time of signing informed consent

2. Upon central biopsy reading process: diagnosis of NASH according to the Steatosis-Activity-Fibrosis (SAF):

1. Steatosis score =1

2. Activity score: A3 or A4

3. Fibrosis score: F2 or F3

3. No qualitative change in dose for the drugs listed below:

1. Antidiabetic treatment if glucagon-like peptide-1 receptor agonists (GLP1 receptor agonists) or sodium-glucose co-transporter-2 inhibitors (SGLT2 inhibitors): for at least 3 months

2. Vitamin E (if at a dose =400 IU/day): for at least 6 months

3. Statins: for at least 3 months

4. No qualitative change in dose for all other chronically administered drugs for at least 3 months prior to Screening

5. Weight stable for 6 months prior to Screening and between the qualifying liver biopsy and Baseline (no more than 5% change for both periods)

6. Negative serum pregnancy test at study Screening for females of childbearing potential confirmed by central laboratory. Females of childbearing potential must practice a consistent and proper use of highly effective method of contraception throughout the study and for 1 month after treatment discontinuation.

Exclusion Criteria:

Liver-related:

1. Documented causes of chronic liver disease other than NASH

2. Histologically documented liver cirrhosis (fibrosis stage F4)

3. History or current diagnosis of hepatocellular carcinoma (HCC)

4. History of or planned liver transplant

5. Positive human immunodeficiency virus (HIV) serology

6. ALT or AST >5 × ULN

7. AST<0.6 ULN if the liver biopsy has to be performed in the scope of the study

8. Abnormal synthetic liver function as defined by Screening central laboratory evaluation

9. Haemoglobin <110 g/L (11 g/dL) for females and <120 g/L (12 g/dL) for males

10. Patient currently receiving any approved treatment for NASH or obesity

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

12. Treatment with drugs that may cause non-alcoholic fatty liver disease (NAFLD) administered for at least 2 weeks within 12 months prior to qualifying liver biopsy

Glycaemia related:

13. HbA1c >9% at Screening

14. Diabetes mellitus other than type 2

15. Current treatment with insulin

16. Treatment with PPAR-gamma agonists (thiazolidinediones [TZDs]) 12 months before screening or historical biopsy.

Obesity related:

17. Bariatric surgery: Restrictive procedures are allowed, if performed >6 months prior to the qualifying liver biopsy; malabsorptive procedures and procedures combining both restrictive and malabsorptive methods are not allowed within 5 years of the qualifying liver biopsy.

Cardiovascular related:

18. History of heart failure with reduced left ventricular ejection fraction (LVEF)

19. Atrial fibrillation requiring anticoagulation

20. Unstable heart failure

21. Uncontrolled hypertension at Screening (values >160/100 mm Hg)

General safety:

22. Women currently breastfeeding

23. Previous exposure to lanifibranor

24. Participation in any clinical trial investigational medicinal product/device within 3 months from Screening or 5 half-lives from Screening, whichever is longer

25. Concomitant treatment with PPAR-alpha agonists (fibrates)

Related Conditions & MeSH terms

• Fatty Liver
• Fibrosis
• NASH - Nonalcoholic Steatohepatitis
• Non-alcoholic Fatty Liver Disease

Intervention

Drug:
• IVA337
A total of 1000 patients will be randomised to receive lanifibranor (800 mg/day) or lanifibranor (1200 mg/day), or matching placebo, employing a 1:1:1 randomisation scheme, respectively, without interruption between Part A and Part B.
• Placebo
A total of 1000 patients will be randomised to receive lanifibranor (800 mg/day) or lanifibranor (1200 mg/day), or matching placebo, employing a 1:1:1 randomisation scheme, respectively, without interruption between Part A and Part B.

Locations

Country	Name	City	State
Argentina	Hospital Británico de Buenos Aires	Buenos Aires
Argentina	Hospital De Alta Complejidad en Red El Cruce	Buenos Aires	Buenos Aries
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autónoma De Buenos Aires	Buenos Aires
Argentina	Hospital Italiano La Plata	La Plata	Buenos Aires
Argentina	Hospital Universitario Austral	Pilar	Buenos Aires
Argentina	Hospital Provincial del Centenario	Rosario	Santa Fe
Australia	Eastern Health - Australia	Box Hill	Victoria
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Gallipoli Medical Research Foundation	Greenslopes	Queensland
Australia	Austin Health	Heidelberg	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Campbelltown Hospital	Liverpool	New South Wales
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	John Hunter Hospital	New Lambton	New South Wales
Australia	Nepean Hospital	Penrith	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Austria	Medizinische Universität Innsbruck	Innsbruck	Tyrol
Belgium	Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan	Brugge	West-Vlaanderen
Belgium	Cliniques Universitaires Saint-Luc	Brussel
Belgium	Hôpital Erasme	Bruxelles	Bruxelles Capitale
Belgium	Universitair Ziekenhuis Antwerpen	Edegem	Antwerpen
Belgium	Ziekenhuis Oost-Limburg - Campus Sint-Jan	Genk	Limburg
Belgium	Algemeen Ziekenhuis Maria Middelares	Gent	Oost-Vlaaderen
Belgium	Universitair Ziekenhuis Gent	Gent	Oost-Vlaanderen
Belgium	Universitair Ziekenhuis Leuven - Campus Gasthuisberg	Leuven	Flemish Brabant
Belgium	Centre Hospitalier Universitaire de Liège Site Sart Tilman	Liège
Belgium	Algemeen Ziekenhuis Delta - Campus Rumbeke	Roeselare	West-Vlaanderen
Belgium	Vitaz	Sint-Niklaas	Oost-Vlaanderen
Brazil	Hospital das Clinicas da Universidade Federal de Minas Gerais	Belo Horizonte	Minas Gerais
Brazil	Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo	Cerqueira César	Sao Paulo
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital Ernesto Dornelles	Porto Alegre	Rio De Janeiro
Brazil	Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto	Ribeirão Preto	São Paulo
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José Do Rio Preto	São Paulo
Bulgaria	Acibadem City Clinic Tokuda Hospital	Sofia
Bulgaria	Diagnostic Consultative Center Aleksandrovska	Sofia
Bulgaria	Diagnostic Consulting Center 20 - Sofia ???d	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment and Emergency Medicine N.I. Pirogov	Sofia	Sofia City
Bulgaria	University Multiprofile Hospital for Active Treatment St. Ivan Rilski	Sofia	Sofia City
Bulgaria	Nov Rehabilitatsionen Tsentar EOOD	Stara Zagora
Bulgaria	Medical Center Medica Plus	Veliko Tarnovo
Canada	William Osler Health System - Brampton Civic Hospital	Brampton	Ontario
Canada	Heritage Medical Research Centre	Calgary	Alberta
Canada	St. Joseph's Healthcare Hamilton - Charlton Campus	Hamilton	Ontario
Canada	McGill University Health Centre	Montréal	Quebec
Canada	Centre de Médecine Métabolique de Lanaudière	Terrebonne	Quebec
Canada	University Health Network	Toronto	Ontario
Canada	Toronto Digestive Disease Associates	Vaughan	Ontario
Chile	Hospital San Juan de Dios de La Serena	La Serena	Coquimbo
Chile	Pontificia Universidad Católica de Chile - Escuela de Medicina	Santiago
Chile	Centro De Investigaciones Clínicas Viña Del Mar	Viña Del Mar	Valparaíso
China	Beijing Ditan Hospital, Capital Medical University	Beijing	Beijing
China	Beijing You'an Hospital,Capital Medical University	Beijing	Fengtai
China	Peking University First Hospital	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun
China	Xiangya Hospital - Central South University	Changsha
China	Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital	Chengdu	Sichuan Shi
China	West china hospital Sichuan University	Chengdu
China	Chongqing university three gorges hospital	Chongqing	Chongging
China	First Affiliated Hospital of the Army Military Medical University (Southwest Hospital)	Chongqing	Chongging
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing
China	Second Affiliated Hospital of Dalian Medical University	Dalian
China	Mengchao Hepatobiliary Hospital of FuJian Medical University	Fuzhou
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian
China	Guangdong Provincial people's hospital	Guangzhou
China	Guangzhou First People's Hospital	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	The Eighth Affiliated Hospital,GuangZhou Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital Sun Yat-sen University	Guangzhou	Guangdong
China	The Third Affiliated Hospital, Sun Yat-Sen University	Guangzhou
China	Guizhou Provincial People's Hospital	Guiyang	Guizhou
China	The Affiliated Hospital of Guizhou Medical University	Guiyang	Guizhou
China	Sir Run Run Shaw Hospital of Zhejiang University School of Medicine - Qingchun Campus	Hangzhou
China	The First Affiliated Hospital , Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Fourth Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	General Hospital of Tianjin Medical University	Heping
China	The First People's Hospital of Yunnan Province	Kunming	Yunnan
China	The First Hospital of Lanzhou University	Lanzhou	Gansu
China	The First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangsu Provincial People's Hospital	Nanjing	Jiangsu
China	The Second Hospital of Nanjing	Nanjing	Jiangsu
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Affiliated Hospital of Nantong University	Nantong	Jiangsu
China	The First Affiliated Hospital of Nanyang Medical College	Nanyang	Henan
China	Ningbo No.2 Hospital (Hwa Mei Hospital)	Ningbo
China	Qingdao Central Hospital	Qingdao	Shandong
China	Qingdao Municipal Hospital	Qingdao
China	RuiAn People's Hospital - Ruixiang Branch	Ruian	Zhejiang
China	Sanmenxia Central Hospital	Sanmenxia	Henan
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai
China	First Affiliated Hospital of China Medical University	Shenyang	Liaoning
China	Shengjing Hospital of China Medical University	Shenyang
China	The Sixth People' s Hospital Of ShenYang	Shenyang	Liaoning
China	The University of Hong Kong-Shenzhen Hospital	Shenzhen
China	The Fifth People's Hospital of Suzhou	Suzhou	Jiangsu
China	Xu, Jun The First Hospital of Shanxi Medical University Taiyun Shanxi	Taiyuan	Shanxi
China	The Second Hospital of Tianjin Medical University	Tianjin	Tianjin
China	Tianjin Third Central Hospital	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei
China	Wuxi No.5 People's Hospital	Wuxi	Jiangsu
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	Xi'an International Medical Center	Xi'an	Shaanxi
China	Henan Provincal People's Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou
China	The Sixth People's Hospital of Zhengzhou	Zhengzhou	Henan
China	Zhengzhou First People's Hospital	Zhengzhou	Henan
China	Zhengzhou People's Hospital	Zhengzhou
China	Third People's Hospital of Zhenjiang	Zhenjiang	Jiangsu
Czechia	Research Site s.r.o.	Plzen
Czechia	Synexus Czech - DRS Prague	Praha
France	Centre Hosptitalier Universitaire d'Angers	Angers	Maine-et-Loire
France	Centre Hosptitalier Universitaire d'Angers	Angers Cedex 9	Maine-et-Loire
France	CHRU de Besançon - Hôpital Jean-Minjoz	Besançon	Franche-Comté
France	Centre Hospitalier Universitaire Estaing	Clermont-Ferrand	Puy-de-Dôme
France	Hôpitaux Universitaires Paris Nord Val-de-Seine - Hôpital Beaujon	Clichy	Ile-de-France
France	Hôpitaux Universitaires Henri Mondor	Créteil	Ile-de-France
France	CHU Dijon Bourgogne - Hôpital François Mitterrand	Dijon	Cantal
France	Centre Hospitalier Universitaire Grenoble Alpes	Grenoble	Isère
France	CHU de Lille - Hôpital Claude Huriez	Lille	Hauts-de-France
France	CHU de Limoges	Limoges	Limousin
France	Hôpital de la Croix Rousse	Lyon	Rhône-Alpes
France	Hôpital Saint-Joseph	Marseille	Bouches-du-Rhône
France	CHU Saint-Eloi	Montpellier	Occitanie
France	Centre Hospitalier Universitaire De Nantes - Hôpital Nord Laennec	Nantes	Loire Atlantique
France	Centre Hospitalier Universitaire De Nantes - Hôpital Nord Laennec	Nantes	Nantes Cedex 1
France	Hôpital l'Archet	Nice	Provence-Alpes-Côte d'Azur
France	Hôpital Cochin	Paris
France	Hôpital Saint-Antoine	Paris	Ile-de-France
France	Hôpital Universitaire Pitié Salpêtrière	Paris	Ile-de-France
France	Hôpital Haut-Lévêque	Pessac	Nouvelle-Aquitaine
France	Hôpital Haut-Lévêque	Pessac	Nouvelle-Aquitaine
France	Centre Hospitalier Universitaire de Rennes	Rennes	Ille-et-Vilaine
France	Hôpital Hautepierre	Strasbourg	Bas-Rhin
France	Clinique Pasteur	Toulouse	Occitanie
France	Hôpital Rangueil	Toulouse	Occitanie
France	Hôpitaux de Brabois	Vandœuvre-lès-Nancy	Lorraine
France	Hôpitaux de Brabois	Vandœuvre-lès-Nancy	Lorraine
France	Hôpitaux Universitaires Paris-Sud - Hôpital Paul Brousse	Villejuif	Ile-de-France
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	EPIMED	Berlin
Germany	Gastroenterologie am Bayerischen Platz	Berlin
Germany	Klinikum Chemnitz	Chemnitz	Sachsen
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden	Sachsen
Germany	Gastroenterologische Gemeinschaftspraxis Herne	Herne	Nordrhein-Westfalen
Germany	Universitätsklinikum des Saarlandes	Homburg	Saarland
Germany	Klinische Forschung Karlsruhe GmbH	Karlsruhe	Baden-Württemberg
Germany	Uniklinik Köln	Köln
Germany	Eugastro	Leipzig	Sachsen
Germany	Universitätsklinikum Schleswig-Holstein - Campus Lübeck	Lübeck	Schleswig-Holstein
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz	Mainz	Rheinland-Pfalz
Germany	Universitätsklinikum Düsseldorf	Northeim
Germany	St. Josefs-Hospital Wiesbaden	Wiesbaden	Hessen
Hungary	Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet	Budapest
Hungary	High Tech Medical Kft.	Budapest
Hungary	MIND Klinika	Budapest
Hungary	SYNEXUS Magyarország Egészségügyi Szolgáltató KFT	Budapest	Central Hungary
Hungary	Debreceni Egyetem Klinikai Központ Kenézy Gyula Campus	Debrecen	Hajdú-Bihar
Hungary	Synexus Magyarország Egészségügyi Szolgáltató Kft. - Debrecen	Debrecen	Hajdu-Bihar County
Israel	Soroka Medical Center	Be'er Sheva	Southern District
Israel	Carmel Medical Center	Haifa	Haifa District
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah University Hospital Ein Kerem	Jerusalem	Jerusalem District
Israel	Shaare Zedek Medical Center	Jerusalem	Jerusalem District
Israel	Western Galilee Hospital-Nahariya	Nahariya	Northern District
Israel	The Chaim Sheba Medical Center	Ramat Gan	Tel Aviv
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv	Gush Dan
Italy	Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi	Bologna
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milan
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano	Milan
Italy	Università degli Studi di Napoli Federico II	Napoli
Italy	Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara	Novara
Italy	Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Roma
Italy	UOSD Interdipartimentale Degenza Medica a ciclo breve	Roma
Italy	Ospedale Casa Sollievo della Sofferenza	San Giovanni Rotondo	Foggia
Italy	Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino	Torino
Mexico	Centro de Investigacion y Gastroenterologia, S.C.	Ciudad de Mexico
Mexico	Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ)	Ciudad de México
Mexico	Centro de Investigación y Gastroenterología	Cuauhtémoc	Ciudad De México
Mexico	PanAmerican Clinical Research Mexico - Cuernavaca	Cuernavaca	Morelos
Mexico	Centro de Investigacion Medico Biologica y Terapia Avanzada	Guadalajara	Jalisco
Mexico	Medical Care and Research S.A. de C.V.	Mérida	Yucatan
Mexico	Medical Care and Research S.A. de C.V.	Mérida	Yucatan
Mexico	Consultorio de la Dra. Maria Sarai Gonzalez Huezo	Metepec
Mexico	Instituto de Seguridad Social del Estado de Mexico y Municipios	Metepec
Mexico	Oaxaca Site Management Organization S.C.	Metepec
Mexico	Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V.	Mexico City
Mexico	Hospital Universitario "Dr. José Eleuterio González" (Servicio de Endocrinología)	Monterrey
Mexico	Hospital Universitario "Dr. Jose Eleuterio Gonzalez" (Servicio de Gastroenterologia)	Monterrey
Mexico	Hospital Universitario Doctor José Eleuterio Gonzalez	Monterrey	Nuevo León
Mexico	Hospital Universitario Dr. José Eleuterio González	Monterrey
Mexico	Hospital Universitario Dr. José Eleuterio González	Monterrey
Mexico	Investigaciones Medicas Cisneros	Monterrey	Nuevo León
Mexico	Oaxaca Site Management Organization S.C.	Oaxaca
Mexico	PanAmerican Clinical Research S.A. de C.V.	Querétaro
Mexico	Hospital Regional de Alta Especialidad de Zumpango	Zumpango
Netherlands	Amsterdam Universitair Medische Centra - Vrije Universiteit Medisch Centrum	Amsterdam	Noord-Holland
Netherlands	Radboud Universitair Medisch Centrum	Nijmegen	Gelderland
Netherlands	Erasmus Medisch Centrum	Rotterdam	Zuid-Holland
Netherlands	Franciscus Gasthuis & Vlietland	Rotterdam
Netherlands	Elisabeth-TweeSteden Ziekenhuis	Tilburg	North Brabant
Netherlands	Ziekenhuis Bernhoven	Uden	North Brabent
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Poland	Synexus - Czestochowa	Czestochowa	Slaskie
Poland	Synexus Polska Sp. z o.o. Oddzial w Gdansku	Gdansk
Poland	Synexus - Gdynia	Gdynia	Pomorskie
Poland	Centrum Medyczne Pratia - Katowice	Katowice	Slaskie
Poland	Synexus - Katowice	Katowice	Slaskie
Poland	Synexus - Lódz	Lódz	Lódzkie
Poland	ID Clinic	Myslowice	Silesian Voivodeship
Poland	Synexus - Poznan	Poznan	Wielkopolskie
Poland	Synexus - Warszawa	Warszawa	Mazowieckie
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Centrum Badan Klinicznych	Wroclaw	Dolnoslaskie
Poland	Synexus - Wroclaw	Wroclaw	Dolnoslaskie
Portugal	Hospital de Braga	Braga
Portugal	Hospital da Senhora da Oliveira - Guimarães	Guimarães	Braga
Portugal	Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa Maria	Lisboa
Portugal	Centro Hospitalar Universitário De São João	Porto
Portugal	Hospital Pedro Hispano	Senhora Da Hora
Portugal	Unidade Local Saúde Alto Minho - Hospital de Santa Luzia	Viana Do Castelo
Portugal	Centro Hospitalar de Trás-Os-Montes e Alto-Douro - Hospital de S. Pedro	Vila Real
Puerto Rico	Fundación de Investigación de Diego Clinical Research	San Juan
South Africa	Synexus - Mediclinic Southern Africa - Constantiaberg	Cape Town	Western Cape
South Africa	Sefako Makgatho Health Sciences University	Pretoria	Gauteng
South Africa	Synexus Clinical Research SA- Watermeyer	Pretoria
South Africa	Synexus - Helderberg Clinical Research Centre - Somerset West	Somerset West	Western Cape
Spain	Hospital Universitario Fundación Alcorcón	Alcorcón	Madrid
Spain	Complejo Hospitalario Torrecárdenas	Almería
Spain	Hospital Germans Trias i Pujol	Badalona
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebrón	Barcelona
Spain	Complejo Asistencial Universitario de Leon	León
Spain	Clínica Universidad de Navarra	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario Son Espases	Palma De Mallorca	Balearic Islands
Spain	Complejo Hospitalario De Pontevedra	Pontevedra
Spain	Consorci Corporació Sanitària Parc Taulí de Sabadell	Sabadell	Barcelona
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria
Spain	Hospital Clínico Universitario de Santiago	Santiago de Compostela	La Coruña
Spain	Hospital Universitario Virgen de Valme	Sevilla
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Consorci Hospital General Universitari de València	Valencia
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitario Rio Hortega	Valladolid
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
Spain	Hospital Universitario Miguel Servet	Zaragoza
Ukraine	Medical Center Center of Family Medicine Plus, LLC	Kyiv
Ukraine	Medical Center Edelweiss Medics, LLC	Kyiv
Ukraine	Medical Center Medbud-Clinic, LLC	Kyiv
United Kingdom	Panthera Biopartners - Glasgow	Glasgow	North Lanarkshire
United Kingdom	Barts Health NHS Trust	London	England
United Kingdom	King's College Hospital NHS Foundation Trust	London	England
United Kingdom	Panthera Biopartners - North London	London	England
United Kingdom	Royal Free London NHS Foundation Trust	London
United Kingdom	Panthera Biopartners - Manchester	Manchester	England
United Kingdom	Panthera Biopartners - Manchester	Manchester	England
United Kingdom	The Newcastle Upon Tyne Hospitals NHS Foundation Trust	Newcastle Upon Tyne	England
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham	England
United Kingdom	Panthera Biopartners - Preston	Preston	England
United Kingdom	Sheffield Teaching Hospitals NHS FT	Sheffield	England
United Kingdom	Royal Surrey County Hospital NHS Foundation Trust	Surrey Quays	England
United States	MedBio Trials	Adventura	Florida
United States	Southwest Gastroenterology Associates	Albuquerque	New Mexico
United States	Investigative Clinical Research - Annapolis	Annapolis	Maryland
United States	Pinnacle Research Group	Anniston	Alabama
United States	Texas Clinical Research Institute	Arlington	Texas
United States	Athens Gastroenterology Association	Athens	Georgia
United States	Digestive Healthcare of Georgia	Atlanta	Georgia
United States	Research and Education Foundation of Atlanta Medical Center	Atlanta	Georgia
United States	Accelemed Research Institute	Austin	Texas
United States	Pinnacle Clinical Research - Austin	Austin	Texas
United States	Office of Franco Felizarta, MD	Bakersfield	California
United States	Mercy Medical Center - Mcauley Plaza	Baltimore	Maryland
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Gastroenterology Associates - Baton Rouge	Baton Rouge	Louisiana
United States	Gadolin Research	Beaumont	Texas
United States	Objective Health - Birmingham Gastroenterology Associates	Birmingham	Alabama
United States	Excel Medical Clinical Trials, LLC	Boca Raton	Florida
United States	Beth Israel Deaconess Medical Center - Liver Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Synergy Healthcare	Bradenton	Florida
United States	Bridgeport Hospital	Bridgeport	Connecticut
United States	PanAmerican Clinical Research - US Headquarters	Brownsville	Texas
United States	South Texas Research Institute - Brownsville	Brownsville	Texas
United States	State University of New York - University at Buffalo	Buffalo	New York
United States	University of Vermont Medical Center	Burlington	Vermont
United States	Fomatmedicalresearch	Camarillo	California
United States	Digestive Disease Associates - Catonsville	Catonsville	Maryland
United States	Velocity Clinical Research - Austin	Cedar Park	Texas
United States	The Institute For Liver Health - Chandler	Chandler	Arizona
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Charlotte Gastroenterology and Hepatology - Randolph Road Office	Charlotte	North Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Clinical Research Institute of Michigan	Chesterfield	Michigan
United States	Galen Research	Chesterfield	Missouri
United States	Chevy Chase Clinical Research	Chevy Chase	Maryland
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	GW Research	Chula Vista	California
United States	Precision Research Institute	Chula Vista	California
United States	Velocity Clinical Research, Chula Vista	Chula Vista	California
United States	Consultants for Clinical Research - Montgomery Office	Cincinnati	Ohio
United States	Gastro Florida	Clearwater	Florida
United States	Tampa Bay Medical Research	Clearwater	Florida
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Heartland Medical Research	Clive	Iowa
United States	Oracle Clinical Research	College Park	Georgia
United States	Gastro Center of Maryland - Columbia	Columbia	Maryland
United States	Gastrointestinal (GI) Associates L.L.P.	Columbia	Missouri
United States	Aventiv Research - Columbus	Columbus	Ohio
United States	IACT Health	Columbus	Georgia
United States	The Ohio State University	Columbus	Ohio
United States	ObjectiveGI - Northeast GI Research	Concord	North Carolina
United States	ARcare Center for Clinical Research - Conway	Conway	Arkansas
United States	Hi Tech and Global Research, LLC	Coral Gables	Florida
United States	American Research Institute, INC	Cutler Bay	Florida
United States	JY Research Institute Inc.	Cutler Bay	Florida
United States	Top Medical Research	Cutler Bay	Florida
United States	GI Alliance - Texas Digestive Disease Consultants - Fort Worth - Downtown	Dallas	Texas
United States	Liver Center of Texas	Dallas	Texas
United States	The Liver Institute at Methodist Dallas	Dallas	Texas
United States	Southeast Clinical Research Center	Dalton	Georgia
United States	Digestive Specialists - Dayton	Dayton	Ohio
United States	Soma Clinical Trials	Denison	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Digestive Health Specialist of the Southeast	Dothan	Alabama
United States	Lone Peak Family Health	Draper	Utah
United States	Ohio Gastroenterology Group, Inc. - Olentangy Office	Dublin	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	South Texas Research Institute - Edinburg	Edinburg	Texas
United States	TriWest Research Associates	El Cajon	California
United States	Gastro Clinic	El Paso	Texas
United States	South Denver Gastroenterology - Swedish Medical Center Office	Englewood	Colorado
United States	Gastroenterology Associates of Northern Virginia	Fairfax	Virginia
United States	NECCR Prima Care Research, LLC	Fall River	Massachusetts
United States	Inova Medical Group - Fairfax Hospital	Falls Church	Virginia
United States	Cumberland Research Associates	Fayetteville	North Carolina
United States	Gastrointestinal Associates & Endoscopy Center - Flowood	Flowood	Mississippi
United States	Care United Medical Center - Forney	Forney	Texas
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Cure Clinical Research, LLC	Fountain Valley	California
United States	Allure Health, Llc	Friendswood	Texas
United States	SC Clinical Research	Garden Grove	California
United States	Digestive Health Associates of Texas - Rockwall	Garland	Texas
United States	Advanced Medical Trials	Georgetown	Texas
United States	Summitt - Pinnacle Clinical Research - Georgetown	Georgetown	Texas
United States	Gastro One - Germantown Office - Wolf Park Drive	Germantown	Tennessee
United States	Mid-Atlantic GI Research	Greenbelt	Maryland
United States	Carolina Digestive Diseases	Greenville	North Carolina
United States	Meritus Center for Clinical Research	Hagerstown	Maryland
United States	ASHA Clinical Research - Munster	Hammond	Indiana
United States	Doral Medical Research, LLC	Hialeah	Florida
United States	Palmetto Research	Hialeah	Florida
United States	Tandem Clinical Research GI	Houma	Louisiana
United States	Alpha Research Institute, LLC	Houston	Texas
United States	Gastroenterology Consultants - Ellington	Houston	Texas
United States	Headlands - Centex Studies - Westfield	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	Houston Research Institute (HRI)	Houston	Texas
United States	Liver Associates of Texas	Houston	Texas
United States	Liver Specialists of Texas	Houston	Texas
United States	Liver Specialists of Texas	Houston	Texas
United States	Pioneer Research Solutions	Houston	Texas
United States	National Research Institute - Santa Ana	Huntington Park	California
United States	Grand Teton Research Group, PLLC	Idaho Falls	Idaho
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Arizona Digestive Health - Sun City	Kansas City	Kansas
United States	Kansas City Research Institute	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	University of Kansas Medical Center Research Institute	Kansas City	Kansas
United States	Combined Gastro Research LLC	Lafayette	Louisiana
United States	Regional Infectious Diseases and Infusion Center	LaGrange	Georgia
United States	Florida Research Institute	Lakewood Ranch	Florida
United States	The Clinical Trials Network - Gastro Care Institute	Lancaster	California
United States	Sierra Clinical Research - Las Vegas	Las Vegas	Nevada
United States	Emeritas Research Group	Leesburg	Virginia
United States	Galenus Group	Lehigh Acres	Florida
United States	University of Kentucky	Lexington	Kentucky
United States	ARcare Center for Clinical Research	Little Rock	Arkansas
United States	Arkansas Diagnostic Center	Little Rock	Arkansas
United States	National Research Institute - Westlake	Los Angeles	California
United States	GI Alliance - Lubbock Digestive Disease Associates - Lubbock	Lubbock	Texas
United States	North Alabama GI Research Center llc	Madison	Alabama
United States	Accel Research Sites	Maitland	Florida
United States	Centor for Advanced Gastroenterology - Main Office - Maitland	Maitland	Florida
United States	Topography Health, Inc.	Manassas	Virginia
United States	GI Alliance - Mansfield	Mansfield	Texas
United States	Tandem Clinical Research	Marrero	Louisiana
United States	Koncord Research - McAllen LLC	McAllen	Texas
United States	Koncord Research-McAllen LLC	McAllen	Texas
United States	Great Lakes Gastroenterology Research - Mentor	Mentor	Ohio
United States	Metropolitan Gastroenterology Associates - Metairie	Metairie	Louisiana
United States	Tandem Clinical Research GI, LLC	Metairie	Louisiana
United States	Clinical Trials Services Corporation	Miami	Florida
United States	D&H National Research Centers	Miami	Florida
United States	Florida Vascular Research	Miami	Florida
United States	Future Care Solution	Miami	Florida
United States	Gastro Health - Galloway	Miami	Florida
United States	Genoma Research Group	Miami	Florida
United States	Life Medical Research Group	Miami	Florida
United States	Miami Dade Medical Research Institute	Miami	Florida
United States	Optimus U Corporation	Miami	Florida
United States	Pro Live Medical Research	Miami	Florida
United States	Schiff Center for Liver Diseases	Miami	Florida
United States	USPA Advance Concept Medical Research Group	Miami	Florida
United States	Froedtert and Medical College of Wisconsin	Milwaukee	Wisconsin
United States	MNGI Digestive Health - Northeast Minneapolis Clinic	Minneapolis	Minnesota
United States	Lucas Research, Inc	Morehead City	North Carolina
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale School of Medicine	New Haven	Connecticut
United States	Advanced Research Institute	New Port Richey	Florida
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Tandem Clinical Research - New York Clinic	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Bon Secours Liver Institute of Hampton Roads	Newport News	Virginia
United States	Digestive & Liver Disease Specialists	Norfolk	Virginia
United States	Arkansas Gastroenterology	North Little Rock	Arkansas
United States	Sensible Healthcare Clinical Research	Ocoee	Florida
United States	INTEGRIS Baptist Medical Center	Oklahoma City	Oklahoma
United States	AdventHealth Transplant Institute	Orlando	Florida
United States	Digestive and Liver Center of Florida - Orlando	Orlando	Florida
United States	IMIC Research - International Medical Investigations Centers	Palmetto Bay	Florida
United States	National Research Institute - Panorama City	Panorama City	California
United States	California Liver Reearch	Pasadena	California
United States	American Research Centers of Florida	Pembroke Pines	Florida
United States	Pensacola GI Research Center	Pensacola	Florida
United States	Arizona Liver Health - Peoria	Peoria	Arizona
United States	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Veterans Affairs Pittsburgh Healthcare System - University Drive Campus	Pittsburgh	Pennsylvania
United States	Eminat, LLC	Plantation	Florida
United States	NAPA Research	Pompano Beach	Florida
United States	Cadena Care Institute	Poway	California
United States	Prospective Research Innovations Inc.	Rancho Cucamonga	California
United States	Rapid City Medical Center	Rapid City	South Dakota
United States	Stanford University Medical Center	Redwood City	California
United States	Inland Empire Liver Foundation	Rialto	California
United States	GI Select Health Research, LLC	Richmond	Virginia
United States	Hunter Holmes Mcguire Veterans Affairs Medical Center - Richmond	Richmond	Virginia
United States	Virginia Commonwealth University	Richmond	Virginia
United States	SKYCRNG - Quinn Healthcare	Ridgeland	Mississippi
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	SSM Health Saint Louis University Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine in St. Louis	Saint Louis	Missouri
United States	University of Utah School of Medicine	Salt Lake City	Utah
United States	Pinnacle Clinical Research - San Antonio	San Antonio	Texas
United States	Quality Research - San Antonio	San Antonio	Texas
United States	Sun Research Institute	San Antonio	Texas
United States	Texas Liver Institute/American Research Corporation	San Antonio	Texas
United States	University of California San Diego	San Antonio	Texas
United States	Research and Education, Inc.	San Diego	California
United States	California Pacific Medical Center Research Institute	San Francisco	California
United States	Quest Clinical Research	San Francisco	California
United States	Silicon Valley Research Institute	San Jose	California
United States	Covenant Metabolic Specialists LLC - Sarasota	Sarasota	Florida
United States	Liver Institute Northwest	Seattle	Washington
United States	Sherman Clinical Research	Sherman	Texas
United States	Louisiana Research Center LLC	Shreveport	Louisiana
United States	NorthShore University HealthSystem	Skokie	Illinois
United States	Richmond University Medical Center	Staten Island	New York
United States	Palmetto Clinical Research	Summerville	South Carolina
United States	Tampa General Hospital	Tampa	Florida
United States	Clinical Trial Management Services	Thousand Oaks	California
United States	Kansas Medical Clinic - Gastroenterology	Topeka	Kansas
United States	Adobe Gastroenterology	Tucson	Arizona
United States	Arizona Digestive Health - Sun City	Tucson	Arizona
United States	Arizona Liver Health	Tucson	Arizona
United States	Del Sol Research Management - Tucson East	Tucson	Arizona
United States	Options Health Research	Tulsa	Oklahoma
United States	San Fernando Valley Health Institute	Van Nuys	California
United States	Digestive Health Research of Central Texas	Waco	Texas
United States	Impact Research Institute	Waco	Texas
United States	GI Alliance - Bay Area Gastroenterology - Webster	Webster	Texas
United States	Tranquil Clinical Research	Webster	Texas
United States	GI Alliance - Gastroenterology Associates of Florida - Wellington	Wellington	Florida
United States	Clinovacare Medical Clinical Research Center	West Columbia	South Carolina
United States	North Shore Gastroenterology	Westlake	Ohio
United States	Cleveland Clinic Florida	Weston	Florida
United States	Digestive Health Research of North Texas	Wichita Falls	Texas
United States	Gastroenterology of the Piedmont, PA - Salem Office	Winston-Salem	North Carolina
United States	Gastroenterology Associates of Western Michigan	Wyoming	Michigan
United States	University of Michigan Health-West Hospital	Wyoming	Michigan
United States	Florida Medical Clinic - Zephyrhills	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Inventiva Pharma

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Mexico,  Netherlands,  Poland,  Portugal,  Puerto Rico,  South Africa,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Resolution of NASH and improvement of fibrosis	Part A: DBPC: Resolution of NASH and improvement of fibrosis at Week 72, defined by NASH CRN scores for ballooning of 0 and inflammation of 0 to 1, and fibrosis score =1 stage decrease compared to Baseline	Part A: Date of randomisation until the date of biopsy at Week 72
Primary	Safety Analyses	Part B: ATE: Using the DBPC on-treatment period, comparing the 2 active arms versus placebo; Using the DBPC +ATE on treatment periods, assessing the 2 active arms. For adverse events, adjudicated liver events, and DILI and MACE events, in addition to the raw cumulative incidence proportions, the exposure-adjusted incidence rates will be provided based on the time patients are at risk.	48 weeks after completion of DBPC period