Phase 3 Study to Evaluate the Efficacy and Safety of Elafibranor Versus Placebo in Patients With Nonalcoholic Steatohepatitis (NASH)

Inclusion Criteria

• •1. Males or females aged from 18 to 75 years inclusive at first screening visit.
• •2. Must provide signed written informed consent and agree to comply with the study protocol.
• •3. Females participating in this study must be of nonchildbearing potential or using highly efficient contraception for the full duration of the study and for 1 month after the end of treatment, as described below:
• •1. Cessation of menses for at least 12 months due to ovarian failure,
• •2. Surgical sterilization such as bilateral oopherectomy, hysterectomy, or medically documented ovarian failure
• •3. If requested by local IRB regulations and/or National laws, sexual abstinence may be considered adequate (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
• •4. Using a highly effective nonhormonal method of contraception (bilateral tubal occlusion, vasectomized partner, or intra-uterine device)
• •5. Double contraception with barrier AND highly effective hormonal method of contraception (oral, intravaginal, or transdermal combined estrogen and progestogen hormonal contraception associated with inhibition of ovulation; oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation; or intrauterine hormone-releasing system). The hormonal contraception must be started at least 1 month prior to Randomization.
• •4. Histological confirmation of steatohepatitis on a diagnostic liver biopsy by central reading of the slides (biopsy obtained within 6 months prior to randomization or during the screening period) with at least 1 in each component of the NAS score (steatosis scored 0-3, ballooning degeneration scored 0-2, and lobular inflammation scored 0-3).
• •5. NAS score ≥4.
• •6. Fibrosis stage of 1 or greater and below 4, according to the NASH CRN fibrosis staging system.
• •7. Stable dose of vitamin E, polyunsaturated fatty acids, or ursodeoxycholic acid from at least 6 months prior to diagnostic liver biopsy
• •8. For participants with type 2 diabetes, glycemia must be controlled. If glycemia is controlled by antidiabetic drugs, change in anti-diabetic therapy must follow these requirements:
• •1. No qualitative change 6 months prior to diagnostic liver biopsy up to Randomization (i.e., implementation of a new anti-diabetic therapy) for participants treated with metformin, gliptins, sulfonylureas, sodium/glucose cotransporter (SGLT) 2 inhibitors, glucagon-like peptide (GLP)-1 agonists, or insulin. Dose changes of these medications are allowed in the 6 months prior to diagnostic liver biopsy, except for GLP-1 agonists, which must remain on stable dose in the 6 months prior to diagnostic liver biopsy.
• •2. No implementation of GLP-1 agonists and SGLT2 inhibitors up to 72 weeks of treatment (Visit 7).
• •Initiation of any other antidiabetic drugs is allowed after Randomization based on treating physicians' judgment, except for glitazones which are prohibited 6 months prior to diagnostic liver biopsy until the end of treatment.