Phase 2b Study in NASH to Assess IVA337

NCT03008070 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IVA_01_337_HNAS_16_0022016-001979-70
• Study Type: interventional
• Target: 247
• Locations: 15 countries
• Sites: 84

Brief Summary

Non-alcoholic steatohepatitis, abbreviated as NASH, is a chronic liver disease that may progress to cirrhosis. The disease is mostly associated with obesity and type 2 diabetes mellitus, or insulin resistance and is very common. However, Treatment of NASH is a significant unmet clinical need. IVA337 (lanifibranor) is a next generation pan-PPAR (peroxisome proliferator-activated receptors) agonist addressing the pathophysiology of NASH : metabolic, inflammatory and fibrotic. The purpose of this research is to evaluate the efficacy and the safety of two doses of IVA337 (800mg, 1200 mg) per day for 24 weeks versus placebo in adult NASH patients with liver steatosis and moderate to severe necroinflammation without cirrhosis.

Conditions

Non-Alcoholic Steatohepatitis (NASH)

Keywords

Non-Alcoholic Steatohepatitis; NASH; peroxisome proliferator-activated receptor (PPAR); Liver Diseases; Fibrosis; Fatty Liver; Non-alcoholic Fatty Liver Disease; Digestive System Diseases; IVA337

Outcome Measures

Primary Outcomes (1)

• SAF Activity Score (SAF-A) Decrease of at Least 2 Points With no Worsening of the CRN Fibrosis Score (CRN-F)

  SAF-A is the activity part of the Steatosis Activity Fibrosis \[SAF\] histological score, calculated as the sum of lobular inflamation score and balloning score. No worsening of fibrosis means that the CRN fibrosis score (CRN-F) remains stable or decreases.

  24 weeks

Secondary Outcomes (27)

• NASH Improvement

  24 weeks

• NASH Resolution and no Worsening of Fibrosis

  24 weeks

• Improvement of Fibrosis by at Least 1 Stage and no Worsening of NASH

  24 weeks

• Activity (SAF-A) Improvement

  24 weeks

• Steatosis (CRN-S) Improvement

  24 weeks

Study Arms (3)

IVA337 1200mg

EXPERIMENTAL

IVA337 400mg, once a day (Quaque Die, QD) with food

Drug: IVA337

IVA337 800mg

EXPERIMENTAL

IVA337 400mg, once a day (Quaque Die, QD) with food

Drug: IVA337

Placebo

PLACEBO COMPARATOR

Placebo to match, once a day (Quaque Die, QD) with food

Drug: Placebo

Interventions

IVA337 DRUG

1200mg

IVA337 1200mg

Placebo DRUG

Placebo to match

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult subjects, age ≥18 years.
• NASH histological diagnosis according to the currently accepted definition of both EASL and AASLD, requiring the combined presence of steatosis (any degree ≥ 5%) + lobular inflammation of any degree + liver cell ballooning of any amount, on a liver biopsy performed ≤ 6 months before screening in the study or at screening and confirmed by central reading during the screening period and
• SAF Activity score of 3 or 4 (\>2)
• SAF Steatosis score ≥ 1
• SAF Fibrosis score \< 4
• Subject agrees to have a liver biopsy performed after 24 weeks of treatment.
• Compensated liver disease
• No other causes of chronic liver disease (autoimmune, primary biliary cholangitis, Hepatitis B virus (HBV), hepatitis C virus (HCV), Wilson's, α-1-antitrypsin deficiency, hemochromatosis, etc…).
• If applicable, have a stable type 2 diabetes, defined as HbA1c ≤ 8.5% and fasting glycemia \<10 mmol/L, no changes in medication in the previous 6 months, and no new symptoms associated with decompensated diabetes in the previous 3 months.
• Have a stable weight since the liver biopsy was performed defined by no more than a 5 % loss of initial body weight.
• Negative pregnancy test or post-menopausal. Women with childbearing potential (i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile) must be using a highly effective method of contraception (i.e. combined (estrogen and progestogen containing) hormonal/ progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner). The contraceptive method will have to be followed for at least one menstruation cycle after the end of the study
• Subjects having given her/his written informed consent.

You may not qualify if:

• Evidence of another form of liver disease.
• History of sustained excess alcohol ingestion: daily alcohol consumption \> 30 g/day (3 drinks per day) for males and \> 20 g/day (2 drinks per day) for females.
• Unstable metabolic condition: Weight change \> 5kg in the last three months, diabetes with poor glycemic control (HbA1c \> 8.5%), introduction of an antidiabetic or of an anti-obesity drug/malabsorptive or restrictive bariatric (weight loss) surgery in the past 6 months prior to screening.
• History of gastrointestinal malabsorptive bariatric surgery within less than 5 years or ingestion of drugs known to produce hepatic steatosis including corticosteroids, high-dose estrogens, methotrexate, tetracycline or amiodarone in the previous 6 months.
• Significant systemic or major illnesses other than liver disease, including congestive heart failure (class C and D of the American Heart Association , AHA), unstable coronary artery disease, cerebrovascular disease, pulmonary disease, renal failure, organ transplantation, serious psychiatric disease, malignancy that, in the opinion of the investigator, would preclude treatment with IVA337 and/or adequate follow up.
• HB antigen \>0, HCV Polymerase chain reaction (PCR) tests \>0 (patients with a history of HCV infection can be included if HCV PCR is negative since more than 3 years), HIV infection.
• Pregnancy/lactation or inability to adhere to adequate contraception in women of child-bearing potential.
• Active malignancy except cutaneous basocellular carcinoma.
• Any other condition which, in the opinion of the investigator would impede competence or compliance or possibly hinder completion of the study.
• Body mass index (BMI) \>45 kg/m2.
• Type 1 diabetes and type 2 diabetic patient on insulin.
• Diabetic ketoacidosis
• Fasting Triglycerides \> 300 mg/dL.
• Hemostasis disorders or current treatment with anticoagulants.
• Contra-indication to liver biopsy.

Sponsors & Collaborators

• Inventiva Pharma: lead

Study Sites (85)

North Alabama GI Research Center

Madison, Alabama, 35758, United States

Location

ACTRI

La Jolla, California, 92037, United States

Location

National Research Institute

Los Angeles, California, 90057, United States

Location

Palmetto Research, LLC

Hialeah, Florida, 33016, United States

Location

Florida Digestive Health Specialists, LLP

Lakewood Rch, Florida, 34211, United States

Location

Northeast GI Research Division

Concord, Massachusetts, 29027, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Carolina's Center for Liver Disease/CHG

Huntersville, North Carolina, 28078, United States

Location

Jefferson University hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Digestive Health Research, LLC

Hermitage, Tennessee, 37076, United States

Location

The Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Digestive Health Research, LLC

San Antonio, Texas, 78229, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Flinders Medical Centre Department of Hepatology

Bedford Park, SA 5042, Australia

Location

Monash Medical Centre

Clayton, 3168, Australia

Location

Lyell McEwin Hospital & The University of Adelaide

Elizabeth Vale, SA 5112, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Australia

Location

Fiona Stanley Hospital

Murdoch, WA 6150, Australia

Location

Medical University Vienna

Vienna, 1090, Austria

Location

Hopital Erasme

Brussels, 1070, Belgium

Location

Clinique Universitaire Saint-luc

Brussels, 1200, Belgium

Location

Antwerp University Hospital

Edegem, 2650, Belgium

Location

Ziekenhuis Oost Limburg

Genk, Belgium

Location

UZ Gent

Ghent, Belgium

Location

"DCC Alexandrovska", EOOD

Sofia, Bulgaria

Location

Acibadem City Clinic Tokuda Hospital

Sofia, Bulgaria

Location

Acibadem City Clinic University Hospital EOOD

Sofia, Bulgaria

Location

MHAT "Sveta Anna" Sofia

Sofia, Bulgaria

Location

Military Medical Academy - MHAT

Sofia, Bulgaria

Location

UMHAT "Sv. Ivan Rilski"

Sofia, Bulgaria

Location

UMHAT "Tsaritsa Yoanna-ISUL"

Sofia, Bulgaria

Location

University of Calgary

Calgary, Canada

Location

The Bailey Health Clinic

Edmonton, Canada

Location

CISSS de la Montérégie Centre

Greenfield Park, Canada

Location

University of Western Ontario, London Health Sciences Centre

London, Canada

Location

McGill University Health Centre (MUHC)

Montreal, Canada

Location

Medpharmgene, Inc

Montreal, Canada

Location

LAIR Centre

Vancouver, Canada

Location

Researchsite S.R.O.

Pilsen, 30100, Czechia

Location

Klin Med S.R.O.

Prague, 1200, Czechia

Location

Institut klinické a experimentální medicíny, IKEM

Prague, 14021, Czechia

Location

CHU Angers

Angers, 49933, France

Location

CHRU Besançon

Besançon, 25000, France

Location

Centre Hospitalier de Bordeaux

Bordeaux, France

Location

CHU Henri Mondor

Créteil, France

Location

CHU de Grenoble

Grenoble, France

Location

Hôpital de La Croix Rousse

Lyon, France

Location

Centre Hospitalier Régional Universitaire de Montpellier

Montpellier, France

Location

CHU de Nice

Nice, 06202, France

Location

Hôpital Saint Antoine

Paris, 75012, France

Location

Hôpital La Pitié Salpétrière

Paris, 75013, France

Location

Hôpital Beaujon

Paris, France

Location

Centre Hospitalier Universitaire de Rennes

Rennes, France

Location

Hôpital de Hautepierre

Strasbourg, France

Location

Hôpital Purpan - Centre Hospitalier Universitaire (CHU) de Toulouse

Toulouse, France

Location

RWTH University Hospital

Aachen, 52074, Germany

Location

Innere Medizin II - Universitätsklinik Freiburg

Freiburg im Breisgau, Germany

Location

Medizinischen Klinik IV

Heidelberg, 69120, Germany

Location

Universitätsmedizin Mainz, I. Med. Klinik

Mainz, 55131, Germany

Location

Universitätsklinikum Münster

Münster, Germany

Location

University Hospital Würzburg

Würzburg, 97080, Germany

Location

Ospedali Riuniti di Ancona-Università Politecnica delle Marche

Ancona, 60126, Italy

Location

Granda Ospedale Maggiore Policlinico - Università di Milano

Milan, 20122, Italy

Location

Pol. Giaccone

Palermo, 90127, Italy

Location

Fondazione Policlinico Agostino Gemelli

Roma, 00168, Italy

Location

Poliambulatorio Giovanni Paolo II

San Giovanni Rotondo, Italy

Location

A.O. Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

CAP Research

Quatre Bornes, Mauritius

Location

Oddzial Gastroenterologii Hepatologii UCK

Katowice, Poland

Location

Katedra i Klinika Chorób Zakaźnych i Hepatologii Uniwersytetu Medycznego w Łodzi

Lodz, 91-347, Poland

Location

Klinika Chorób Zakaźnych

Lublin, 20-081, Poland

Location

Centrum Badan Klinicznych

Wroclaw, Poland

Location

General hospital Celje

Celje, Slovenia

Location

General Hospital Murska Sobota

Murska Sobota, Slovenia

Location

Vall d'Hebron Hospital

Barcelona, Spain

Location

Hospital Puerta de Hierro MAJADAHONDA

Madrid, 28222, Spain

Location

Virgen de la Victoria University Hospital

Málaga, 29010, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

Universitätsklinik für Viszerale Chirurgie und Medizin

Bern, Switzerland

Location

Epatocentro Ticino

Lugano, 6900, Switzerland

Location

Kings College Hospital NHS Foundation Trust

London, United Kingdom

Location

Freeman Hospital, Newcastle University

Newcastle, NE7 7DN, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

Location

Related Publications (4)

• Boursier J, Herve H, Roux M, Abdelmalek MF, Francque SM, Broqua P, Junien JL, Abitbol JL, Huot-Marchand P, Dzen L, Cooreman MP, Patel S. Biomarkers of Histological Response in Lanifibranor-treated Patients With Metabolic Dysfunction-associated Steatohepatitis. Clin Gastroenterol Hepatol. 2025 Dec;23(13):2499-2508.e8. doi: 10.1016/j.cgh.2024.12.039. Epub 2025 Mar 17.

  PMID: 40107637 DERIVED

• Cooreman MP, Butler J, Giugliano RP, Zannad F, Dzen L, Huot-Marchand P, Baudin M, Beard DR, Junien JL, Broqua P, Abdelmalek MF, Francque SM. The pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis. Nat Commun. 2024 May 10;15(1):3962. doi: 10.1038/s41467-024-47919-9.

  PMID: 38730247 DERIVED

• Francque SM, Bedossa P, Ratziu V, Anstee QM, Bugianesi E, Sanyal AJ, Loomba R, Harrison SA, Balabanska R, Mateva L, Lanthier N, Alkhouri N, Moreno C, Schattenberg JM, Stefanova-Petrova D, Vonghia L, Rouzier R, Guillaume M, Hodge A, Romero-Gomez M, Huot-Marchand P, Baudin M, Richard MP, Abitbol JL, Broqua P, Junien JL, Abdelmalek MF; NATIVE Study Group. A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH. N Engl J Med. 2021 Oct 21;385(17):1547-1558. doi: 10.1056/NEJMoa2036205.

  PMID: 34670042 DERIVED

• Sven M F, Pierre B, Manal F A, Quentin M A, Elisabetta B, Vlad R, Philippe HM, Bruno S, Jean-Louis J, Pierre B, Jean-Louis A. A randomised, double-blind, placebo-controlled, multi-centre, dose-range, proof-of-concept, 24-week treatment study of lanifibranor in adult subjects with non-alcoholic steatohepatitis: Design of the NATIVE study. Contemp Clin Trials. 2020 Nov;98:106170. doi: 10.1016/j.cct.2020.106170. Epub 2020 Oct 8.

  PMID: 33038502 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Diseases; Fibrosis; Fatty Liver; Digestive System Diseases

Interventions

lanifibranor

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr Michael Cooreman, Chief Medical Officer
• Organization: Inventiva S.A.

native.public@inventivapharma.com

+33380447616

Study Officials

• Sven FRANCQUE, MD, PhD

  Division of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2016
• First Posted: January 2, 2017
• Study Start: February 7, 2017
• Primary Completion: February 20, 2020
• Study Completion: March 16, 2020
• Last Updated: July 19, 2023
• Results First Posted: April 12, 2021

Record last verified: 2023-07

Locations

CZ (3); US (14); BE (5); MA (1); BU (7); AU (5); PL (4); ES (5); GB (3); CA (7); FR (14); IT (6); SL (2); CH (2); DE (6)