Phase 2b Study in NASH to Assess IVA337 (NATIVE)

This is an interventional treatment trial for Non-Alcoholic Steatohepatitis (NASH) focused on measuring Non-Alcoholic Steatohepatitis, NASH, peroxisome proliferator-activated receptor (PPAR), Liver Diseases, Fibrosis, Fatty Liver, Non-alcoholic Fatty Liver Disease, Digestive System Diseases, IVA337 Read More

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, 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.

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.