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出境医 / 临床实验 / Study to Evaluate the Effect of Elafibranor on Hepatic Lipid Composition in Subjects With Nonalcoholic Fatty Liver (NAFL)
Study to Evaluate the Effect of Elafibranor on Hepatic Lipid Composition in Subjects With Nonalcoholic Fatty Liver (NAFL)
Study Description
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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non-Alcoholic Fatty Liver | Drug: elafibranor 120mg Drug: Placebo | Phase 2 |
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 17 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Intervention Model Description: | Randomized, double-blind, cross-over (placebo or elafibranor [GFT505]) placebo-controlled study |
| Masking: | Quadruple (Participant, Care Provider, 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. |
| Primary Purpose: | Treatment |
| Official Title: | A Double-Blind, Placebo-Controlled, Cross-over Phase II Study to Evaluate the Effect of a 6-week Elafibranor (120mg) Treatment Administered Once Daily on Hepatic Lipid Composition in Subjects With Nonalcoholic Fatty Liver (NAFL) |
| Actual Study Start Date : | August 16, 2019 |
| Actual Primary Completion Date : | March 11, 2020 |
| Actual Study Completion Date : | July 14, 2020 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
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Experimental: elafibranor 120mg followed by placebo
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
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Drug: elafibranor 120mg
elafibranor 120mg is a coated tablet for oral administration, once daily
Other Name: GFT505
Drug: Placebo Placebo is a coated tablet for oral administration, once daily
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Placebo Comparator: placebo followed by elafibranor 120mg
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
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Drug: elafibranor 120mg
elafibranor 120mg is a coated tablet for oral administration, once daily
Other Name: GFT505
Drug: Placebo Placebo is a coated tablet for oral administration, once daily
|
Outcome Measures
Primary Outcome Measures :
- Change in relative amount of saturated fatty acids in the liver [ Time Frame: 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 Outcome Measures :
- Change in hepatic insulin sensitivity [ Time Frame: After 6 weeks ]Hepatic insulin sensitivity measured by Hepatic Glucose Production (HGP) at the end of 6 weeks treatment period
- Glucose homeostasis markers [ Time Frame: After 6 weeks ]Fasting glycemia
- Glucose homeostasis markers [ Time Frame: After 6 weeks ]HbA1c
- Glucose homeostasis markers [ Time Frame: After 6 weeks ]Fasting insulinemia
- Glucose homeostasis markers [ Time Frame: After 6 weeks ]C-peptide
- Glucose homeostasis markers [ Time Frame: After 6 weeks ]Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index
- Glucose homeostasis markers [ Time Frame: After 6 weeks ]Fructosamine
- Lipid metabolism markers [ Time Frame: After 6 weeks ]Triglycerides (TG)
- Lipid metabolism markers [ Time Frame: After 6 weeks ]Total cholesterol (TC)
- Lipid metabolism markers [ Time Frame: After 6 weeks ]High density lipoprotein-cholesterol (HDL-C)
- Lipid metabolism markers [ Time Frame: After 6 weeks ]Low density lipoprotein-cholesterol (LDL-C)
- Lipid metabolism markers [ Time Frame: After 6 weeks ]Non-HDL-C
- Lipid metabolism markers [ Time Frame: After 6 weeks ]Free fatty acid (FFA)
- Inflammatory markers [ Time Frame: After 6 weeks ]High sensitivity C-reactive protein (hs-CRP)
- Inflammatory markers [ Time Frame: After 6 weeks ]Fibrinogen
- Inflammatory markers [ Time Frame: After 6 weeks ]Haptoglobin
- Liver function [ Time Frame: After 6 weeks ]Alanine aminotransferase (ALT)
- Liver function [ Time Frame: After 6 weeks ]Aspartate aminotransferase (AST)
- Liver function [ Time Frame: After 6 weeks ]Gamma glutamyl transferase (GGT)
- Liver function [ Time Frame: After 6 weeks ]Alkaline phosphatase (ALP)
- Liver function [ Time Frame: After 6 weeks ]Total and conjugated bilirubin
- Renal function [ Time Frame: After 6 weeks ]Creatinine
- Renal function [ Time Frame: After 6 weeks ]Estimated glomerular filtration rate (using Modification of Diet in Renal Disease (MDRD) formula)
- Renal function [ Time Frame: After 6 weeks ]Blood urea nitrogen
- Renal function [ Time Frame: After 6 weeks ]Albumin
- Renal function [ Time Frame: After 6 weeks ]Uric acid
- Renal function [ Time Frame: After 6 weeks ]Total proteins
- Body weight [ Time Frame: After 6 weeks ]
- Body Mass Index [ Time Frame: After 6 weeks ]
- Waist circumference [ Time Frame: After 6 weeks ]
- Incidence and severity of treatment emergent adverse events (TEAEs) and their relationship to study drug [ Time Frame: After 6 weeks ]
- Incidence of clinically meaningful changes from baseline in safety laboratory parameters, and vital signs [ Time Frame: After 6 weeks ]
Eligibility Criteria
| Ages Eligible for Study: | 40 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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 exclusion criteria:
- Positive anti-human immunodeficiency virus (HIV) antibody
- Positive hepatitis B surface antigen
- Positive hepatitis C Virus (HCV) antibody
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >5 x upper limit of normal (ULN)
- Conjugated bilirubin > 1.50mg/dL due to altered hepatic function Note: Gilbert Disease subjects are allowed into the study
- International normalized ratio >1.40 due to altered hepatic function
- Platelet count <100,000/mm^3 due to portal hypertension
- Serum creatinine levels >1.53 mg/dL in males and >1.24 mg/dL in females
- Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as subjects with markers of kidney damage or estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m^2)
- Unexplained serum creatine phosphokinase (CPK) >2 x ULN. In case of explained elevated CPK >2 x ULN, the measurement can be repeated prior to Randomization. In this case, retest should be performed within 1 to 2 weeks after initial test. A CPK retest >2 x ULN leads to exclusion
- Hemoglobin A1c (HbA1C) > 6.4% and/or fasting plasma glucose (FGP) > 126 mg/dl
Contacts and Locations
Locations
| Netherlands | |
| NUTRIM School of Nutrition and Translational Research in Metabolism | |
| Maastricht, Netherlands | |
Sponsors and Collaborators
Genfit
Investigators
| Study Director: | Pascal Birman, MD | Genfit |
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | May 15, 2019 | ||||
| First Posted Date ICMJE | May 16, 2019 | ||||
| Last Update Posted Date | August 31, 2020 | ||||
| Actual Study Start Date ICMJE | August 16, 2019 | ||||
| Actual Primary Completion Date | March 11, 2020 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
Change in relative amount of saturated fatty acids in the liver [ Time Frame: 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
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| Original Primary Outcome Measures ICMJE | Same as current | ||||
| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | Study to Evaluate the Effect of Elafibranor on Hepatic Lipid Composition in Subjects With Nonalcoholic Fatty Liver (NAFL) | ||||
| Official Title ICMJE | A Double-Blind, Placebo-Controlled, Cross-over Phase II Study to Evaluate the Effect of a 6-week Elafibranor (120mg) Treatment Administered Once Daily on Hepatic Lipid Composition in Subjects With Nonalcoholic Fatty Liver (NAFL) | ||||
| 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 | ||||
| Detailed Description | Not Provided | ||||
| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Phase 2 | ||||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Crossover Assignment Intervention Model Description: Randomized, double-blind, cross-over (placebo or elafibranor [GFT505]) placebo-controlled study Masking: Quadruple (Participant, Care Provider, 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. |
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| Condition ICMJE | Non-Alcoholic Fatty Liver | ||||
| Intervention ICMJE |
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Terminated | ||||
| Actual Enrollment ICMJE |
17 | ||||
| Original Estimated Enrollment ICMJE |
16 | ||||
| Actual Study Completion Date ICMJE | July 14, 2020 | ||||
| Actual Primary Completion Date | March 11, 2020 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria: Medical history:
Concomitant medications and lifestyle:
In addition to the above criteria, subject should not present any of the following biological exclusion criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 40 Years to 75 Years (Adult, Older Adult) | ||||
| Accepts Healthy Volunteers ICMJE | No | ||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
| Listed Location Countries ICMJE | Netherlands | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT03953456 | ||||
| Other Study ID Numbers ICMJE | GFT505-219-8 2019-000645-12 ( EudraCT Number ) |
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| Has Data Monitoring Committee | No | ||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Genfit | ||||
| Study Sponsor ICMJE | Genfit | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE |
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| PRS Account | Genfit | ||||
| Verification Date | August 2020 | ||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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