Purpose

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.

Condition

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Exclusion Criteria

  1. Known heart failure (Grade I to IV of New York Heart Association classification). 2. History of efficient bariatric surgery within 5 years prior to screening. 3. Uncontrolled hypertension during the Screening Period despite optimal antihypertensive therapy 4. Type 1 diabetes participants . 5. Participants with decompensated diabetes (HbA1c>9%). 6. Participants with a history of clinically significant acute cardiac event within 6 months prior to screening 7. Weight loss of more than 5% within 6 months prior to randomization 8. Compensated and decompensated cirrhosis 9. Current or recent history (<5 years) of significant alcohol consumption 10. Pregnant or lactating females or females planning to become pregnant during the study period. 11. Other well documented causes of chronic liver disease according to standard diagnostic procedures 12. Participants with previous exposure to Elafibranor 13. Prohibited concomitant medication 14. Any medical conditions that may diminish life expectancy to less than 2 years including known cancers. 15. Evidence of any other unstable or untreated clinically significant immunological, endocrine, hematological, gastrointestinal, neurological, neoplastic or psychiatric disease. 16. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain. 17. Participants with biological criteria exclusion as per effective protocol

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
120 mg Elafibranor
Coated tablets dosed at 120mg Elafibranor; oral administration; one tablet per day before breakfast with a glass of water
  • Drug: Elafibranor
    Other names:
    • GFT505
Placebo Comparator
Placebo
Coated placebo tablets; oral administration; one tablet per day before breakfast with a glass of water
  • Drug: Placebo

More Details

Status
Terminated
Sponsor
Genfit

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.