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 )

Prior treatment

• Patient currently receiving any approved treatment for NASH or obesity
• 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
  • Glycaemia related:
• Current treatment with insulin
• Treatment with PPAR-gamma agonists (thiazolidinediones \[TZDs\]) 12 months before screening or historical biopsy.
  • Obesity related:
• 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.
  • Cardiovascular related:
• Previous exposure to lanifibranor
• Concomitant treatment with PPAR-alpha agonists (fibrates)

Other illness

• Documented causes of chronic liver disease other than NASH
• History of or planned liver transplant
• Positive human immunodeficiency virus (HIV) serology
• Diabetes mellitus other than type 2
• Unstable heart failure
• Uncontrolled hypertension at Screening (values \>160/100 mm Hg)
  • General safety:

Lab values

• ALT or AST \>5 × ULN
• AST\<0.6 ULN if the liver biopsy has to be performed in the scope of the study
• Abnormal synthetic liver function as defined by Screening central laboratory evaluation
• Haemoglobin \<110 g/L (11 g/dL) for females and \<120 g/L (12 g/dL) for males
• HbA1c \>9% at Screening
• History of heart failure with reduced left ventricular ejection fraction (LVEF)

Age

• Current or recent history (\<5 years) of significant alcohol consumption

Other

• Liver-related:
• Histologically documented liver cirrhosis (fibrosis stage F4)
• History or current diagnosis of hepatocellular carcinoma (HCC)
• Atrial fibrillation requiring anticoagulation
• Women currently breastfeeding
• Participation in any clinical trial investigational medicinal product/device within 3 months from Screening or 5 half-lives from Screening, whichever is longer

• Male or female, aged ≥18 years at the time of signing informed consent
• Upon central biopsy reading process: diagnosis of NASH according to the Steatosis-Activity-Fibrosis (SAF):
  • Steatosis score ≥1
  • Activity score: A3 or A4
  • Fibrosis score: F2 or F3
• No qualitative change in dose for the drugs listed below:
  • 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
  • Vitamin E (if at a dose ≥400 IU/day): for at least 6 months
  • Statins: for at least 3 months
• No qualitative change in dose for all other chronically administered drugs for at least 3 months prior to Screening
• Weight stable for 6 months prior to Screening and between the qualifying liver biopsy and Baseline (no more than 5% change for both periods)
• 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.

Criteria the registry did not label

• Prescreening Criteria:
• Diagnosed with NASH on prior liver biopsy
• Type 2 diabetes with high waist circumference or obesity or hepatic steatosis on ultrasound
• At least 3 of the components of metabolic syndrome