Ensayos clínicos

Inclusion Criteria:

• Males or females aged from 18 to 75 years inclusive at first screening visit.
• 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:
  • Cessation of menses for at least 12 months due to ovarian failure, Surgical sterilization such as bilateral oopherectomy, hysterectomy, or medically
    documented ovarian failure;
  • 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)'
  • Using a highly effective nonhormonal method of contraception (bilateral tubal occlusion, vasectomized partner, or intra-uterine device);
  • 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.
• Histological confirmation of steatohepatitis on a diagnostic liver biopsy by central reading of the
  slides (biopsy obtained within 6 months prior to Screening or during the Screening Period) with
  at least 1 in each component of the NAS (steatosis scored 0-3, ballooning degeneration scored 0-2, and lobular inflammation scored 0-3).
• NAS ≥ 4.
• Fibrosis stage of 1 or greater and below 4, according to the NASH CRN fibrosis staging system.
  For patients with fibrosis stage 1, only patients at high risk of progression will be included
  meaning with a NAS ≥ 5 and at least 2 of the following conditions: persistent elevated ALT
  (absence of normal value of ALT within the past year), obesity defined by a BMI ≥ 30, metabolic
  syndrome (NCEP ATP III definition), type 2 diabetes, or HOMA-IR > 6.
• Patients in whom it is safe and practical to proceed with a liver biopsy, and who agree to have:
  • 1 liver biopsy during the Screening Period for diagnostic purpose (if no historical biopsy
    within 6 months before Screening is available);
  • 1 liver biopsy after 72-weeks of treatment for assessment of the treatment effects on NASH;
  • a final liver biopsy after approximately 4 years of treatment (V13), unless a liver biopsy has already been performed within the past year;
  • 1 liver biopsy performed only in the case of suspicion of cirrhosis (to have a histological
    confirmation).
• If a patient is treated with 1 of the following drugs: vitamin E (> 400 IU/day), polyunsaturated fatty acids (>2 g/day), or ursodeoxycholic acid; a stable dose from at least 6 months prior to
  diagnostic liver biopsy is required.
• For patients with type 2 diabetes, glycemia must be controlled. If glycemia is controlled by
  antidiabetic drugs, change in anti-diabetic therapy must follow these requirements:
  • no qualitative change 6 months prior to diagnostic liver biopsy up to Randomization (i.e., implementation of a new anti-diabetic therapy) for patients 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;
  • no implementation of GLP-1 agonists and SGLT2 inhibitors up to 72 weeks of treatment V7).
• 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.

Exclusion Criteria:

• Known heart failure (Grade I to IV of New York Heart Association classification).
• History of efficient bariatric surgery within 5 years prior to screening.
• Uncontrolled hypertension.
• Type 1 diabetes patients.
• Patients with decompensated diabetes (HbA1c>9%).
• Patients with a history of clinically significant acute cardiac event within 6 months prior to screening.
• Weight loss of more than 5% within 6 months prior to randomization.
• Compensated and decompensated cirrhosis.
• Current or recent history (<5 years) of significant alcohol consumption.
• Pregnant or lactating females or females planning to become pregnant during the study period.
• Other well documented causes of chronic liver disease according to standard diagnostic procedures.
• Patients with previous exposure to Elafibranor.
• Prohibited concomitant medication.
• Any medical conditions that may diminish life expectancy to less than 2 years including known cancers.
• Evidence of any other unstable or untreated clinically significant immunological, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric disease.
• Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.