Evaluation de l’efficacité et de la sécurité d’emploi de l’IVA337 chez des patients atteints de stéatose hépatique non alcoolique (SHNA)

Drug: IVA337;Drug: Placebo

Gender: All
Maximum age: N/A
Minimum age: 18 Years

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.