Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03008070
Other study ID # IVA_01_337_HNAS_16_002
Secondary ID 2016-001979-70
Status Completed
Phase Phase 2
First received
Last updated
Start date February 7, 2017
Est. completion date March 16, 2020

Study information

Verified date July 2023
Source Inventiva Pharma
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. 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.


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).


Recruitment information / eligibility

Status Completed
Enrollment 247
Est. completion date March 16, 2020
Est. primary completion date February 20, 2020
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - 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, a-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. Exclusion Criteria: - 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. - 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.

Study Design


Related Conditions & MeSH terms

  • Fatty Liver
  • Non-alcoholic Fatty Liver Disease
  • Non-Alcoholic Steatohepatitis (NASH)

Intervention

Drug:
IVA337
1200mg
IVA337
800mg
Placebo
Placebo to match

Locations

Country Name City State
Australia Flinders Medical Centre Department of Hepatology Bedford Park
Australia Monash Medical Centre Clayton
Australia Lyell McEwin Hospital & The University of Adelaide Elizabeth Vale
Australia Royal Brisbane and Women's Hospital Herston
Australia Fiona Stanley Hospital Murdoch
Austria Medical University Vienna Vienna
Belgium Clinique Universitaire Saint-luc Brussels
Belgium Hopital Erasme Brussels
Belgium Antwerp University Hospital Edegem
Belgium Ziekenhuis Oost Limburg Genk
Belgium UZ Gent Gent
Bulgaria "DCC Alexandrovska", EOOD Sofia
Bulgaria Acibadem City Clinic Tokuda Hospital Sofia
Bulgaria Acibadem City Clinic University Hospital EOOD Sofia
Bulgaria MHAT "Sveta Anna" Sofia Sofia
Bulgaria Military Medical Academy - MHAT Sofia
Bulgaria UMHAT "Sv. Ivan Rilski" Sofia
Bulgaria UMHAT "Tsaritsa Yoanna-ISUL" Sofia
Canada University of Calgary Calgary
Canada The Bailey Health Clinic Edmonton
Canada CISSS de la Montérégie Centre Greenfield Park
Canada University of Western Ontario, London Health Sciences Centre London
Canada McGill University Health Centre (MUHC) Montréal
Canada Medpharmgene, Inc Montréal
Canada LAIR Centre Vancouver
Czechia Researchsite S.R.O. Plzen
Czechia Institut klinické a experimentální medicíny, IKEM Praha
Czechia Klin Med S.R.O. Praha
France CHU Angers Angers
France CHRU Besançon Besancon
France Centre Hospitalier de Bordeaux Bordeaux
France CHU Henri Mondor Créteil
France CHU de Grenoble Grenoble
France Hôpital de La Croix Rousse Lyon
France Centre Hospitalier Régional Universitaire de Montpellier Montpellier
France CHU de Nice Nice
France Hôpital Beaujon Paris
France Hôpital La Pitié Salpétrière Paris
France Hôpital Saint Antoine Paris
France Centre Hospitalier Universitaire de Rennes Rennes
France Hôpital de Hautepierre Strasbourg
France Hôpital Purpan - Centre Hospitalier Universitaire (CHU) de Toulouse Toulouse
Germany RWTH University Hospital Aachen
Germany Innere Medizin II - Universitätsklinik Freiburg Freiburg
Germany Medizinischen Klinik IV Heidelberg
Germany Universitätsmedizin Mainz, I. Med. Klinik Mainz
Germany Universitätsklinikum Münster Münster
Germany University Hospital Würzburg Wurzburg
Italy Ospedali Riuniti di Ancona-Università Politecnica delle Marche Ancona
Italy Granda Ospedale Maggiore Policlinico - Università di Milano Milano
Italy Pol. Giaccone Palermo
Italy Fondazione Policlinico Agostino Gemelli Roma
Italy Poliambulatorio Giovanni Paolo II San Giovanni Rotondo
Italy A.O. Città della Salute e della Scienza di Torino Torino
Mauritius CAP Research Quatre Bornes
Poland Oddzial Gastroenterologii Hepatologii UCK Katowice
Poland Katedra i Klinika Chorób Zakaznych i Hepatologii Uniwersytetu Medycznego w Lodzi Lodz
Poland Klinika Chorób Zakaznych Lublin
Poland Centrum Badan Klinicznych Wroclaw
Slovenia General hospital Celje Celje
Slovenia General Hospital Murska Sobota Murska Sobota
Spain Vall d'Hebron Hospital Barcelona
Spain Hospital Puerta de Hierro MAJADAHONDA Madrid
Spain Virgen de la Victoria University Hospital Malaga
Spain Hospital Universitario Marqués de Valdecilla Santander
Spain Hospital Virgen del Rocío Sevilla
Switzerland Universitätsklinik für Viszerale Chirurgie und Medizin Bern
Switzerland Epatocentro Ticino Lugano
United Kingdom Kings College Hospital NHS Foundation Trust London
United Kingdom Freeman Hospital, Newcastle University Newcastle
United Kingdom Nottingham University Hospitals NHS Trust Nottingham
United States University of Virginia Health System Charlottesville Virginia
United States Northeast GI Research Division Concord Massachusetts
United States Duke University Medical Center Durham North Carolina
United States Digestive Health Research, LLC Hermitage Tennessee
United States Palmetto Research, LLC Hialeah Florida
United States Carolina's Center for Liver Disease/CHG Huntersville North Carolina
United States ACTRI La Jolla California
United States Florida Digestive Health Specialists, LLP Lakewood Ranch Florida
United States National Research Institute Los Angeles California
United States North Alabama GI Research Center Madison Alabama
United States Jefferson University hospital Philadelphia Pennsylvania
United States Virginia Commonwealth University Richmond Virginia
United States Digestive Health Research, LLC San Antonio Texas
United States The Texas Liver Institute San Antonio Texas

Sponsors (1)

Lead Sponsor Collaborator
Inventiva Pharma

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Czechia,  France,  Germany,  Italy,  Mauritius,  Poland,  Slovenia,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary Steatosis (CRN-S) Improvement Improvement of CRN Steatosis score (CRN-S) is defined as a decrease of at least 1 point. 24 weeks
Secondary Lobular Inflammation (CRN-I) Improvement Improvement of CRN Lobular inflammation score (CRN-I) is defined as a decrease of at least 1 point. 24 weeks
Secondary Hepatocyte Balooning (CRN-B) Improvement Improvement of CRN Ballooning (CRN-B) is defined as a decrease of at least 1 point. 24 weeks
Secondary Fibrosis (CRN-F) Improvement Improvement of CRN Fibrosis score (CRN-F) is defined as a decrease of at least 1 point. 24 weeks
Secondary Modified ISHAK Fibrosis (ISHAK-F) Improvement Improvement of Modified ISHAK Fibrosis (ISHAK-F) is defined as a decrease of at least 1 point. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. 24 weeks
Secondary 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. From baseline to Week 24.
See also
  Status Clinical Trial Phase
Recruiting NCT04481594 - A Study to Evaluate the Safety and Tolerability of Single and Multiple Ascending Doses of HPN-01 in Healthy Subjects Phase 1
Recruiting NCT06151964 - A Trial to Learn How Safe AZD9550 is in People With Type 2 Diabetes Who Are Overweight or Obese Phase 1/Phase 2
Completed NCT04019561 - A Study to Evaluate Safety and Pharmacodynamic Efficacy of 0382 in Obese Subjects With NAFLD/NASH. Phase 2
Completed NCT01694849 - Phase IIb Study to Evaluate the Efficacy and Safety of GFT505 Versus Placebo in Patients With Non-Alcoholic Steatohepatitis (NASH) Phase 2
Completed NCT02653300 - A Pilot Study to Assess the Safety of Oral Insulin in Patients With Nonalcolholic Steatohepatitis (NASH) Phase 2
Completed NCT03517540 - Study of Safety, Tolerability, and Efficacy of a Combination Treatment of LJN452 and CVC in Adult Patients With NASH and Liver Fibrosis Phase 2
Withdrawn NCT05050721 - Natural History of Non Alcoholic Fatty Liver Disease and Predictors of Advanced Fibrosis
Active, not recruiting NCT04682600 - The Sonic Incytes Liver Incytes System, Evaluation of Liver Fibrosis and Steatosis Versus MRE and MRI PDFF N/A
Enrolling by invitation NCT01950884 - Lifestyle Versus Ezetimibe Plus Lifestyle in Patients With Non-alcoholic Steatohepatitis Phase 4
Completed NCT04483947 - A Study to Assess Safety, Tolerability, PK and PD of AZD2693 in Non-alcoholic Steatohepatitis Patients Phase 1
Completed NCT02927314 - A Study of the Efficacy and Safety of CF102 in the Treatment of Non-Alcoholic Fatty Liver Disease Phase 2
Active, not recruiting NCT02612662 - A Study to Assess the Safety and Tolerability of Single Doses of AZD4076 in Healthy Male Subjects Phase 1
Recruiting NCT06168383 - To Evaluate the Efficacy and Safety of HSK31679 in Chinese Patients With Non-Alcoholic Steatohepatitis (NASH) . Phase 2
Terminated NCT02605616 - Use of a Novel Drug in People With Non-alcoholic Steatohepatitis (NASH) or Non-alcoholic Fatty Liver Disease (NAFLD) Phase 2
Completed NCT02158351 - Gut Microbiota and Modulation of Liver Damage in NAFLD
Recruiting NCT03151473 - Longitudinal Observational Study Of Chinese With NAFLD/NASH
Recruiting NCT04820036 - A Physiologic Analysis of Endoscopic Sleeve Gastroplasty (ESG) N/A
Recruiting NCT05553470 - Study to Evaluate the Effects of Hepatic Impairment on the Pharmacokinetics of Miricorilant Phase 1
Recruiting NCT04639414 - Combined Active Treatment in Type 2 Diabetes With NASH Phase 4
Withdrawn NCT04607655 - A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered GB1211 in Participants With Suspected or Confirmed Non-alcoholic Steatohepatitis (NASH) and Liver Fibrosis Phase 1/Phase 2