Non-Alcoholic Steatohepatitis (NASH)Phase 2NATIVENCT03008070
Phase 2b Study in NASH to Assess IVA337
A Phase 2 study testing IVA337 in people with Non-Alcoholic Steatohepatitis (NASH), run by Inventiva Pharma at 85 sites in 16 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Alcoholic Steatohepatitis (NASH)
- What is being tested?
- IVA337
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 247 participants
- Where
- 85 sitesin 16 countries
- Study dates
- 7 Feb 2017to 16 Mar 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- History of, or current cardiac dysrhythmias and/or a history of cardiovascular disease event, including myocardial infarction, except patients with only well controlled hypertension. Any clinically significant ECG abnormality reported by central ECG reading.
- Participation in any other clinical study within the previous 3 months.
- Have a known hypersensitivity to any of the ingredients or excipients of the Investigational medicinal product (IMP)
- Be possibly dependent on the Investigator or the sponsor (e.g., including, but not limited to, affiliated employee).
- Creatine phosphokinase (CPK)>5 x ULN
- Osteopenia or any other well documented Bone disease. Patient without well documented osteopenia treated with vitamin D and/or Calcium based supplements for preventive reasons can be included.
- (The criteria below are applicable only for patients who will undergo a MRI/LMS in selected centers)
- Claustrophobia to a degree that prevents tolerance of MRI scanning procedure. Sedation is permitted at discretion of investigator.
- Metallic implant of any sort that prevents MRI examination including, but not limited to: aneurysm clips, metallic foreign body, vascular grafts or cardiac implants, neural stimulator, metallic contraceptive device, tattoo, body piercing that cannot be removed, cochlear implant; or any other contraindication to MRI examination.
Trial locations and contacts
85 sites in 16 countries.
85 sites in 16 countries
United States14 sites
University of Virginia Health System
Charlottesville, Virginia, 22908
Northeast GI Research Division
Concord, Massachusetts, 29027
Duke University Medical Center
Durham, North Carolina, 27710
Digestive Health Research, LLC
Hermitage, Tennessee, 37076
Palmetto Research, LLC
Hialeah, Florida, 33016
Carolina's Center for Liver Disease/CHG
Huntersville, North Carolina, 28078
ACTRI
La Jolla, California, 92037
Florida Digestive Health Specialists, LLP
Lakewood Rch, Florida, 34211
National Research Institute
Los Angeles, California, 90057
North Alabama GI Research Center
Madison, Alabama, 35758
Jefferson University hospital
Philadelphia, Pennsylvania, 19107
Virginia Commonwealth University
Richmond, Virginia, 23298
The Texas Liver Institute
San Antonio, Texas, 78215
Digestive Health Research, LLC
San Antonio, Texas, 78229
France14 sites
CHU Angers
Angers, 49933
CHRU Besançon
Besançon, 25000
Centre Hospitalier de Bordeaux
Bordeaux
CHU Henri Mondor
Créteil
CHU de Grenoble
Grenoble
Hôpital de La Croix Rousse
Lyon
Centre Hospitalier Régional Universitaire de Montpellier
Montpellier
CHU de Nice
Nice, 06202
Hôpital Saint Antoine
Paris, 75012
Hôpital La Pitié Salpétrière
Paris, 75013
Hôpital Beaujon
Paris
Centre Hospitalier Universitaire de Rennes
Rennes
Hôpital de Hautepierre
Strasbourg
Hôpital Purpan - Centre Hospitalier Universitaire (CHU) de Toulouse
Toulouse
Bulgaria7 sites
"DCC Alexandrovska", EOOD
Sofia
Acibadem City Clinic Tokuda Hospital
Sofia
Acibadem City Clinic University Hospital EOOD
Sofia
MHAT "Sveta Anna" Sofia
Sofia
Military Medical Academy - MHAT
Sofia
UMHAT "Sv. Ivan Rilski"
Sofia
UMHAT "Tsaritsa Yoanna-ISUL"
Sofia
Canada7 sites
University of Calgary
Calgary
The Bailey Health Clinic
Edmonton
CISSS de la Montérégie Centre
Greenfield Park
University of Western Ontario, London Health Sciences Centre
London
McGill University Health Centre (MUHC)
Montreal
Medpharmgene, Inc
Montreal
LAIR Centre
Vancouver
Germany6 sites
RWTH University Hospital
Aachen, 52074
Innere Medizin II - Universitätsklinik Freiburg
Freiburg im Breisgau
Medizinischen Klinik IV
Heidelberg, 69120
Universitätsmedizin Mainz, I. Med. Klinik
Mainz, 55131
Universitätsklinikum Münster
Münster
University Hospital Würzburg
Würzburg, 97080
Italy6 sites
Ospedali Riuniti di Ancona-Università Politecnica delle Marche
Ancona, 60126
Granda Ospedale Maggiore Policlinico - Università di Milano
Milan, 20122
Pol. Giaccone
Palermo, 90127
Fondazione Policlinico Agostino Gemelli
Roma, 00168
Poliambulatorio Giovanni Paolo II
San Giovanni Rotondo
A.O. Città della Salute e della Scienza di Torino
Torino, 10126
Australia5 sites
Flinders Medical Centre Department of Hepatology
Bedford Park, SA 5042
Monash Medical Centre
Clayton, 3168
Lyell McEwin Hospital & The University of Adelaide
Elizabeth Vale, SA 5112
Royal Brisbane and Women's Hospital
Herston
Fiona Stanley Hospital
Murdoch, WA 6150
Belgium5 sites
Hopital Erasme
Brussels, 1070
Clinique Universitaire Saint-luc
Brussels, 1200
Antwerp University Hospital
Edegem, 2650
Ziekenhuis Oost Limburg
Genk
UZ Gent
Ghent
Spain5 sites
Vall d'Hebron Hospital
Barcelona
Hospital Puerta de Hierro MAJADAHONDA
Madrid, 28222
Virgen de la Victoria University Hospital
Málaga, 29010
Hospital Universitario Marqués de Valdecilla
Santander, 39008
Hospital Virgen del Rocío
Seville, 41013
Poland4 sites
Oddzial Gastroenterologii Hepatologii UCK
Katowice
Katedra i Klinika Chorób Zakaźnych i Hepatologii Uniwersytetu Medycznego w Łodzi
Lodz, 91-347
Klinika Chorób Zakaźnych
Lublin, 20-081
Centrum Badan Klinicznych
Wroclaw
Czechia3 sites
Researchsite S.R.O.
Pilsen, 30100
Klin Med S.R.O.
Prague, 1200
Institut klinické a experimentální medicíny, IKEM
Prague, 14021
United Kingdom3 sites
Kings College Hospital NHS Foundation Trust
London
Freeman Hospital, Newcastle University
Newcastle, NE7 7DN
Nottingham University Hospitals NHS Trust
Nottingham
Slovenia2 sites
General hospital Celje
Celje
General Hospital Murska Sobota
Murska Sobota
Switzerland2 sites
Universitätsklinik für Viszerale Chirurgie und Medizin
Bern
Epatocentro Ticino
Lugano, 6900
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter, Dose-range, Proof-of-concept, 24-week Treatment Study of IVA337 in Adult Subjects With Nonalcoholic Steatohepatitis (NASH)
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.
Read the detailed description
Randomized (stratified on diabetes), placebo-controlled, double-blind, parallel-assignment, dose-range multicenter study
There are 3 parallel treatment groups: placebo, IVA337 800mg once a day (Quaque Die, QD) and IVA337 1200mg QD (identical tablets of 400mg IVA337 or placebo). Both, patient and investigator are blinded.
For each patient, the study duration will be an overall of 6 to 8 months (with a 10-day to 4-week selection period, a 24-week treatment period and a 4-week follow-up period).
- Conditions
- Non-Alcoholic Steatohepatitis (NASH)
- Being tested
- IVA337, Placebo
- Keywords
- Non-Alcoholic Steatohepatitis, NASH, peroxisome proliferator-activated receptor (PPAR), Liver Diseases, Fibrosis, Fatty Liver, Non-alcoholic Fatty Liver Disease, Digestive System Diseases, IVA337
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Liver Diseases, Fibrosis, Fatty Liver, Digestive System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IVA337Drug
1200mg
IVA337Drug
800mg
PlaceboDrug
Placebo to match
| Study group | Role | What they receive |
|---|---|---|
| IVA337 1200mg | Experimental | IVA337 400mg, once a day (Quaque Die, QD) with food Receives: Drug: IVA337 |
| IVA337 800mg | Experimental | IVA337 400mg, once a day (Quaque Die, QD) with food Receives: Drug: IVA337 |
| Placebo | Placebo comparator | Placebo to match, once a day (Quaque Die, QD) with food Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 weeks
Secondary outcomes (27)
NASH Improvement
NASH improvement is defined as a decrease of at least 2 points in NAS score (sum of CRN Steatosis, Inflammation and Ballooning scores) without worsening of CRN Fibrosis score.
Measured: 24 weeks
NASH Resolution and no Worsening of Fibrosis
Resolution of NASH is defined as a CRN Inflammation score equal to 0 or 1, and a CRN Ballooning score equal to 0. No worsening of fibrosis means that the CRN fibrosis score remains stable or decreases.
Measured: 24 weeks
Improvement of Fibrosis by at Least 1 Stage and no Worsening of NASH
Improvement of fibrosis is defined as a decrease of at least one stage in CRN Fibrosis score. No worsening of NASH is defined as no increase of CRN Steatosis score, no increase of CRN Inflammation score ans no increase of CRN Ballooning score.
Measured: 24 weeks
Activity (SAF-A) Improvement
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. Improvement of SAF-A is defined as a decrease of at least 1 point.
Measured: 24 weeks
Steatosis (CRN-S) Improvement
Improvement of CRN Steatosis score (CRN-S) is defined as a decrease of at least 1 point.
Measured: 24 weeks
Lobular Inflammation (CRN-I) Improvement
Improvement of CRN Lobular inflammation score (CRN-I) is defined as a decrease of at least 1 point.
Measured: 24 weeks
Hepatocyte Balooning (CRN-B) Improvement
Improvement of CRN Ballooning (CRN-B) is defined as a decrease of at least 1 point.
Measured: 24 weeks
Fibrosis (CRN-F) Improvement
Improvement of CRN Fibrosis score (CRN-F) is defined as a decrease of at least 1 point.
Measured: 24 weeks
Modified ISHAK Fibrosis (ISHAK-F) Improvement
Improvement of Modified ISHAK Fibrosis (ISHAK-F) is defined as a decrease of at least 1 point.
Measured: 24 weeks
Absolute Change in ALT
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.
Measured: 24 weeks
Absolute Change in AST
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.
Measured: 24 weeks
Absolute Change in GGT
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.
Measured: 24 weeks
Absolute Change in Fibrinogen
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.
Measured: 24 weeks
Absolute Change in Hs-CRP
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.
Measured: 24 weeks
Absolute Change in Alpha2 Macroglobulin
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.
Measured: 24 weeks
Absolute Change in Haptoglobulin
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start.
Measured: 24 weeks
Absolute Change of Fasting Plasma Glucose
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Measured: 24 weeks
Absolute Change in Insulin
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Measured: 24 weeks
Absolute Change in HOMA Index
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Measured: 24 weeks
Absolute Change in HbA1c
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Measured: 24 weeks
Absolute Change in Total Cholesterol
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Measured: 24 weeks
Absolute Change of HDL-Cholesterol
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Measured: 24 weeks
Absolute Change of LDL-Cholesterol
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Measured: 24 weeks
Absolute Change in Triglycerides
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Measured: 24 weeks
Absolute Change in Apo A1
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Measured: 24 weeks
Absolute Change in Adiponectin
Absolute change is defined as Week 24 value - baseline value. Baseline value was defined as the last available non-missing data before or equal to the treatment start. Only fasting values were considered.
Measured: 24 weeks
Resolution of NASH and Improvement of Fibrosis by at Least 1 Stage
Resolution of NASH is defined as a CRN Inflammation score equel to 0 or 1, and a CRN ballooning score equal to 0. Improvement of firbosis is defined as a decrease of at least one stage in CRN Fibrosis score.
Measured: From baseline to Week 24.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2017 (estimated)
- Study start7 Feb 2017
- Primary completion20 Feb 2020
- Study completion16 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Non-Alcoholic Steatohepatitis (NASH)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 247 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inventiva Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Sven FRANCQUE, MD, PhD, Principal investigator, Division of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03008070
- Sponsor's protocol ID
- IVA_01_337_HNAS_16_002
- Other IDs
- 2016-001979-70, 2016
- Acronym
- NATIVE
- Status last verified
- Jul 2023
- First submitted
- 22 Dec 2016
- Last updated
- 19 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 40107637Cooreman 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.
PubMed 38730247Francque 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.
PubMed 34670042Sven 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.
PubMed 33038502
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Multicenter, Dose-range, Proof-of-concept, 24-week Treatment Study of IVA337 in Adult Subjects With Nonalcoholic Steatohepatitis (NASH)
- ClinicalTrials.gov ID
- NCT03008070
- Acronym / sponsor ID
- NATIVE / IVA_01_337_HNAS_16_002
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 247 participants (actual)
- Lead sponsor
- Inventiva PharmaIndustry (pharma, biotech, devices)
- Study start
- 7 Feb 2017 (actual)
- Primary completion
- 20 Feb 2020 (actual)
- Study completion
- 16 Mar 2020 (actual)
- First posted
- 2 Jan 2017 (estimated)
- Results
- Posted 12 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Randomized (stratified on diabetes), placebo-controlled, double-blind, parallel-assignment, dose-range multicenter study
There are 3 parallel treatment groups: placebo, IVA337 800mg once a day (Quaque Die, QD) and IVA337 1200mg QD (identical tablets of 400mg IVA337 or placebo). Both, patient and investigator are blinded.
For each patient, the study duration will be an overall of 6 to 8 months (with a 10-day to 4-week selection period, a 24-week treatment period and a 4-week follow-up period).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| IVA337 1200mg | Experimental | Drug: IVA337IVA337 400mg, once a day (Quaque Die, QD) with food |
| IVA337 800mg | Experimental | Drug: IVA337IVA337 400mg, once a day (Quaque Die, QD) with food |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo to match, once a day (Quaque Die, QD) with food |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
- 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…).
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IVA3371200mg | Drug | IVA337 1200mg |
| IVA337800mg | Drug | IVA337 800mg |
| PlaceboPlacebo to match | Drug | Placebo |
Primary outcome
SAF Activity Score (SAF-A) Decrease of at Least 2 Points With no Worsening of the CRN Fibrosis Score (CRN-F)
Time frame: 24 weeks
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.
27 secondary outcomes
NASH Improvement
Time frame: 24 weeks
NASH Resolution and no Worsening of Fibrosis
Time frame: 24 weeks
Improvement of Fibrosis by at Least 1 Stage and no Worsening of NASH
Time frame: 24 weeks
Activity (SAF-A) Improvement
Time frame: 24 weeks
Steatosis (CRN-S) Improvement
Time frame: 24 weeks
Lobular Inflammation (CRN-I) Improvement
Time frame: 24 weeks
Hepatocyte Balooning (CRN-B) Improvement
Time frame: 24 weeks
Fibrosis (CRN-F) Improvement
Time frame: 24 weeks
Modified ISHAK Fibrosis (ISHAK-F) Improvement
Time frame: 24 weeks
Absolute Change in ALT
Time frame: 24 weeks
Absolute Change in AST
Time frame: 24 weeks
Absolute Change in GGT
Time frame: 24 weeks
Absolute Change in Fibrinogen
Time frame: 24 weeks
Absolute Change in Hs-CRP
Time frame: 24 weeks
Absolute Change in Alpha2 Macroglobulin
Time frame: 24 weeks
Absolute Change in Haptoglobulin
Time frame: 24 weeks
Absolute Change of Fasting Plasma Glucose
Time frame: 24 weeks
Absolute Change in Insulin
Time frame: 24 weeks
Absolute Change in HOMA Index
Time frame: 24 weeks
Absolute Change in HbA1c
Time frame: 24 weeks
Absolute Change in Total Cholesterol
Time frame: 24 weeks
Absolute Change of HDL-Cholesterol
Time frame: 24 weeks
Absolute Change of LDL-Cholesterol
Time frame: 24 weeks
Absolute Change in Triglycerides
Time frame: 24 weeks
Absolute Change in Apo A1
Time frame: 24 weeks
Absolute Change in Adiponectin
Time frame: 24 weeks
Resolution of NASH and Improvement of Fibrosis by at Least 1 Stage
Time frame: From baseline to Week 24.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40107637Boursier 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.
- Derived from this study: PubMed 38730247Cooreman 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.
- Derived from this study: PubMed 34670042Francque 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.
- Derived from this study: PubMed 33038502Sven 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sven FRANCQUE, MD, PhD principal investigator
Division of Gastroenterology and Hepatology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium
85 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IVA337 in people with Non-Alcoholic Steatohepatitis (NASH), run by Inventiva Pharma at 85 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 85 sites in United States, France, Bulgaria, Canada, Germany and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
SAF Activity Score (SAF-A) Decrease of at Least 2 Points With no Worsening of the CRN Fibrosis Score (CRN-F) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03008070, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2023.