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.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 75 YearsSexo: ALL

Criterios de inclusión

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.
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 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).
NAS score ≥4.
Fibrosis stage of 1 or greater and below 4, according to the NASH CRN fibrosis staging system.
Stable dose of vitamin E, polyunsaturated fatty acids, or ursodeoxycholic acid from at least 6 months prior to diagnostic liver biopsy
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:
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.
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.

Criterios de exclusión

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 during the Screening Period despite optimal antihypertensive therapy
Type 1 diabetes participants .
Participants with decompensated diabetes (HbA1c\>9%).
Participants 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
Participants 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.
Participants with biological criteria exclusion as per effective protocol

Ubicaciones

Sanatorio Güemes

Caba, Buenos Aires, Argentina

Axismed S.R.L

CABA, Buenos Aires, Argentina

Instituto de Investigaciones Clinicas San Nicolas SRL

San Nicolás de los Arroyos, Buenos Aires, Argentina

Hospital Alemán

Buenos Aires, Argentina

Centro de Investigación y Prevención Cardiovascular SA (CIPREC)

Buenos Aires, Argentina

Fundación Sanatorio Güemes

Buenos Aires, Argentina

Hospital Italiano de Buenos Aires

Buenos Aires, Argentina

Hospital Británico de Buenos Aires

Buenos Aires, Argentina

CCBR Clinical Research

Buenos Aires, Argentina

Centro De Hepatologia Ciudad de La Plata

La Plata, Argentina

Hospital Universitario Austral

Pilar, Argentina

Dim Clinica Privada

Ramos Mejía, Argentina

Hospital Provincial del Centenario

Rosario, Argentina

Instituto Medico Alas

Salta, Argentina

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

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Elafibranor

Placebo

Ubicaciones

Sanatorio Güemes

Axismed S.R.L

Instituto de Investigaciones Clinicas San Nicolas SRL

Hospital Alemán

Centro de Investigación y Prevención Cardiovascular SA (CIPREC)

Fundación Sanatorio Güemes

Hospital Italiano de Buenos Aires

Hospital Británico de Buenos Aires

CCBR Clinical Research

Centro De Hepatologia Ciudad de La Plata

Hospital Universitario Austral

Dim Clinica Privada

Hospital Provincial del Centenario

Instituto Medico Alas

Patrocinadores