A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 )

Eligibility Criteria

• 1. Male or female, aged ≥18 years at the time of signing informed consent
• 2. Upon central biopsy reading process: diagnosis of NASH according to the Steatosis-Activity-Fibrosis (SAF):
• 1. Steatosis score ≥1
• 2. Activity score: A3 or A4
• 3. Fibrosis score: F2 or F3
• 3. No qualitative change in dose for the drugs listed below:
• 1. Antidiabetic treatment if glucagon-like peptide-1 receptor agonists (GLP1 receptor agonists) or sodium-glucose co-transporter-2 inhibitors (SGLT2 inhibitors): for at least 3 months
• 2. Vitamin E (if at a dose ≥400 IU/day): for at least 6 months
• 3. Statins: for at least 3 months
• 4. No qualitative change in dose for all other chronically administered drugs for at least 3 months prior to Screening
• 5. Weight stable for 6 months prior to Screening and between the qualifying liver biopsy and Baseline (no more than 5% change for both periods)
• 6. Negative serum pregnancy test at study Screening for females of childbearing potential confirmed by central laboratory. Females of childbearing potential must practice a consistent and proper use of highly effective method of contraception throughout the study and for 1 month after treatment discontinuation.
• 1. Documented causes of chronic liver disease other than NASH
• 2. Histologically documented liver cirrhosis (fibrosis stage F4)
• 3. History or current diagnosis of hepatocellular carcinoma (HCC)
• 4. History of or planned liver transplant
• 5. Positive human immunodeficiency virus (HIV) serology
• 6. ALT or AST \>5 × ULN
• 7. AST\<0.6 ULN if the liver biopsy has to be performed in the scope of the study
• 8. Abnormal synthetic liver function as defined by Screening central laboratory evaluation
• 9. Haemoglobin \<110 g/L (11 g/dL) for females and \<120 g/L (12 g/dL) for males
• 10. Patient currently receiving any approved treatment for NASH or obesity
• 11. Current or recent history (\<5 years) of significant alcohol consumption
• 12. Treatment with drugs that may cause non-alcoholic fatty liver disease (NAFLD) administered for at least 2 weeks within 12 months prior to qualifying liver biopsy
• 13. HbA1c \>9% at Screening
• 14. Diabetes mellitus other than type 2
• 15. Current treatment with insulin
• 16. Treatment with PPAR-gamma agonists (thiazolidinediones \[TZDs\]) 12 months before screening or historical biopsy.
• 17. Bariatric surgery: Restrictive procedures are allowed, if performed \>6 months prior to the qualifying liver biopsy; malabsorptive procedures and procedures combining both restrictive and malabsorptive methods are not allowed within 5 years of the qualifying liver biopsy.
• 18. History of heart failure with reduced left ventricular ejection fraction (LVEF)
• 19. Atrial fibrillation requiring anticoagulation
• 20. Unstable heart failure
• 21. Uncontrolled hypertension at Screening (values \>160/100 mm Hg)
• 22. Women currently breastfeeding
• 23. Previous exposure to lanifibranor
• 24. Participation in any clinical trial investigational medicinal product/device within 3 months from Screening or 5 half-lives from Screening, whichever is longer
• 25. Concomitant treatment with PPAR-alpha agonists (fibrates)