Study to Evaluate the Effect of Elafibranor on Hepatic Lipid Composition in Subjects With Nonalcoholic Fatty Liver (NAFL)

NCT03953456 | Terminated Phase 2

• 2 other identifiers: GFT505-219-82019-000645-12
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, double-blind, cross-over (placebo or elafibranor \[GFT505\]) placebo-controlled study, will evaluate the effect on hepatic lipid composition and safety of elafibranor 120 mg quaque die (QD) versus placebo in an adult NAFL population after 6 weeks of treatment with a 4-week wash-out period. This study will achieve mechanistic information about the mode of action of Elafibranor on the (lipid) metabolism in the human fatty liver

Conditions

Non-Alcoholic Fatty Liver

Keywords

Hepatic lipid composition; Elafibranor; Hepatic Glucose Production

Outcome Measures

Primary Outcomes (1)

• Change in relative amount of saturated fatty acids in the liver

  Relative amount of saturated fatty acids (SFA) in the liver measured by Magnetic Resonance Spectroscopy (1H-MRS) at the end of 6 weeks treatment period

  After 6 weeks

Secondary Outcomes (32)

• Change in hepatic insulin sensitivity

  After 6 weeks

• Glucose homeostasis markers

  After 6 weeks

• Glucose homeostasis markers

  After 6 weeks

• Glucose homeostasis markers

  After 6 weeks

• Glucose homeostasis markers

  After 6 weeks

Study Arms (2)

elafibranor 120mg followed by placebo

EXPERIMENTAL

Participants will first receive elafibranor 120mg for 6 weeks. After a washout period of 4-6 weeks, they will then receive placebo for 6 weeks

Drug: elafibranor 120mg; Drug: Placebo

placebo followed by elafibranor 120mg

PLACEBO COMPARATOR

Participants will first receive placebo for 6 weeks. After a washout period of 4-6 weeks, they will then receive elafibranor 120mg for 6 weeks

Drug: elafibranor 120mg; Drug: Placebo

Interventions

elafibranor 120mg DRUG

elafibranor 120mg is a coated tablet for oral administration, once daily

Also known as: GFT505

elafibranor 120mg followed by placebo; placebo followed by elafibranor 120mg

Placebo DRUG

Placebo is a coated tablet for oral administration, once daily

elafibranor 120mg followed by placebo; placebo followed by elafibranor 120mg

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or post-menopausal females aged from 40-75 years inclusive at first Screening Visit. (Post-menopausal defined as: subject should be surgically sterilized at least 6 months or no spontaneous menses for at least 1 year prior to screening)
• Must provide signed written informed consent and agrees to comply with the study protocol.
• Liver fat percentage ≥ 5 percent (as measured with Magnetic Resonance Spectroscopy)
• ≤ BMI ≤ 38.0 kg/m\^2
• Stable dietary habits and physical activity pattern (over 3 months prior to Screening Visit)
• Subject agrees not to change dietary habits and physical activity pattern, to follow diet and lifestyle recommendations and not to consume or use illicit drugs during the study up to end of treatment.

You may not qualify if:

• Medical history:
• Documented weight loss of more than 5 percent during the 6-month period prior to Screening Visit
• Contra-indications for magnetic resonance imaging / spectroscopy
• Known history of Type 1 and 2 diabetes
• Known chronic heart failure (Grade I to IV of New York Heart Association classification)
• History of clinically significant acute cardiac event within 6 months prior to Screening Visit such as: stroke, transient ischemic attack, or coronary heart disease (angina pectoris, myocardial infarction, revascularization procedures)
• Uncontrolled hypertension despite optimal antihypertensive therapy
• Other well documented causes of chronic liver disease according to standard diagnostic procedures.
• Symptoms of clinical depression
• Other concurrent medical (e.g., immunological, neoplastic, endocrine, hematological, gastrointestinal or neurological) or psychiatric condition, which, in the opinion of the Investigator, would place the subject at increased risk, preclude obtaining voluntary consent/assent or compliance with required study procedures, or would confound the objectives of study
• Known hypersensitivity to the investigation product or any of its formulation excipients
• Concomitant medications and lifestyle:
• Fibrates are not permitted from 8 weeks before Screening up to end of treatment. Subjects taking statins or ezetimibe prior to Screening Visit 1 may participate if the dose has been stable for 3 months prior to Screening Visit 1 and no dose adjustments are anticipated
• Currently taking drugs that can induce steatosis/steatohepatitis including, but not restricted to: corticosteroids (parenteral \& oral chronic administration only), amiodarone (Cordarone), tamoxifen (Nolvadex), and methotrexate (Rheumatrex, Trexall), which are not permitted 30 days prior to Screening and up to end of treatment
• Subjects receiving thiazolidinediones (glitazones \[pioglitazone, rosiglitazone\])

Sponsors & Collaborators

• Genfit: lead

Study Sites (1)

NUTRIM School of Nutrition and Translational Research in Metabolism

Maastricht, Netherlands

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Pascal Birman, MD

  Genfit

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The Investigator, subject, and study personnel will be blinded to the treatment. Identification numbers will be assigned to a subject at the Screening Visit. Upon completion of the Screening Visits, eligible subjects will be randomly assigned to Sequence Group A or Group B, defining the order of treatments.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, cross-over (placebo or elafibranor \[GFT505\]) placebo-controlled study

Study Record Dates

• First Submitted: May 15, 2019
• First Posted: May 16, 2019
• Study Start: August 16, 2019
• Primary Completion: March 11, 2020
• Study Completion: July 14, 2020
• Last Updated: August 31, 2020

Record last verified: 2020-08

Locations

NL (1)