A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Study to Evaluate the Efficacy and Safety of Elafibranor in Patients With Nonalcoholic Steatohepatitis (NASH) and Fibrosis
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.
18 Years to 75 Years
Accepting Healthy Volunteers?
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. BMI ≤45 kg/m².
4. Females participating in the study must either not be of childbearing potential (hysterectomy, bilateral oophorectomy, medically documented ovarian failure, or >50 years of age with cessation of menses for at least 12 months due to ovarian failure) or using efficient double contraception: hormonal contraception (including patch, contraceptive ring, etc.), intra-uterine device, or other mechanical contraception method + condom or diaphragm or spermicide for the full duration of the study and for 1 month after the end of treatment.
5. 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).
6. NAS score ≥4.
7. Fibrosis stage of 1 or greater and below 4, according to the NASH CRN fibrosis staging system.
8. Stable dose of vitamin E, polyunsaturated fatty acids, or ursodeoxycholic acid from at least 6 months prior to diagnostic liver biopsy
9. No change in antidiabetic therapy within 6 months prior to liver biopsy
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
4. Type 1 diabetes patients.
5. Patients with decompensated diabetes (HbA1c>9%).
6. Patients 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. Patients 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.