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

Overview

About this study

The primary objectives of this study are to evaluate the effect of Elafibranor treatment compared to placebo on 1) histological improvement and 2) all-cause mortality and liver-related outcomes in patients with nonalcoholic steatohepatitis (NASH) and fibrosis.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Elizabeth Carey, M.D.

Closed for enrollment

Contact information:

Isabel Santana B.S.

(480) 301-9870

Santana.Isabel@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available