Non-Alcoholic Fatty Liver
Conditions
Keywords
Hepatic lipid composition, Elafibranor, Hepatic Glucose Production
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
Interventions
elafibranor 120mg is a coated tablet for oral administration, once daily
DRUGPlacebo
Placebo is a coated tablet for oral administration, once daily
Sponsors
Genfit
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
Randomized, double-blind, cross-over (placebo or elafibranor \[GFT505\]) placebo-controlled study
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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) * 25.0 ≤ 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.
Exclusion criteria
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 \[pioglitazone, rosiglitazone\]) * Currently taking any medication that could interfere with study medication absorption, distribution, metabolism, or excretion or could lead to induction or inhibition of microsomal enzymes, e.g., indomethacin, which are not permitted from Randomization until end of treatment * Any medication use known to interfere with glucose homeostasis/metabolism * Smoking * Current or recent history (\<5years) of significant alcohol consumption. For men, significant consumption is typically defined as higher than 30 g pure alcohol per day. For women, it is typically defined as higher than 20 g pure alcohol per day * Subjects who have donated blood or blood products within the previous month prior to screening or who plan to donate blood or blood products at any time during the trial and in the month following the end of the study * Is participating in any other study and have received any other investigational drug or device within 30 days prior to Screening or are taking part in a non-medication study which, in the opinion of the Investigator, would interfere with study compliance or outcome assessments * Subjects who cannot be contacted in case of emergency In addition to the above criteria, subject should not present any of the following biological
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in relative amount of saturated fatty acids in the liver | After 6 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucose homeostasis markers | After 6 weeks | Fasting glycemia |
| Lipid metabolism markers | After 6 weeks | Triglycerides (TG) |
| Inflammatory markers | After 6 weeks | High sensitivity C-reactive protein (hs-CRP) |
| Liver function | After 6 weeks | Alanine aminotransferase (ALT) |
| Renal function | After 6 weeks | Creatinine |
| Change in hepatic insulin sensitivity | After 6 weeks | Hepatic insulin sensitivity measured by Hepatic Glucose Production (HGP) at the end of 6 weeks treatment period |
| Body Mass Index | After 6 weeks | — |
| Waist circumference | After 6 weeks | — |
| Incidence and severity of treatment emergent adverse events (TEAEs) and their relationship to study drug | After 6 weeks | — |
| Incidence of clinically meaningful changes from baseline in safety laboratory parameters, and vital signs | After 6 weeks | — |
| Body weight | After 6 weeks | — |
Countries
Netherlands
Outcome results
None listed