Non Alcoholic SteatohepatitisPhase 2NCT03883607
Elafibranor, PK and Safety in Children and Adolescents 8 to 17 Years of Age With Non Alcoholic Steatohepatitis (NASH)
A Phase 2 study testing Elafibranor 80mg and Elafibranor 120mg in people with Non Alcoholic Steatohepatitis, run by Genfit at 2 sites in United States.
Trial summary
The study was being conducted in order to assess the pharmacokinetics and the safety of elafibranor following once daily administration of two dose levels of elafibranor (80 milligrams [mg] and 120mg) during 3 months in children and adolescent population (8 to 17 years of age) with non alcoholic steatohepatitis (NASH). Read more about this study
- Who is it for?
- Ages 8 to 17 years
- Conditions the study is for
- Non Alcoholic Steatohepatitis
- What is being tested?
- Elafibranor 80mg and Elafibranor 120mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- 25 Jun 2019to 16 Jun 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Was male or female between 8 and 17 years of age (inclusive) at the time of Screening Visit (when consent for study participation is given) and at the time of Randomization;
- Diagnosis of NASH confirmed by histological evaluation (with or without fibrosis) from a liver biopsy obtained within 24 months prior to Randomization;
- Had an alanine aminotransferase (ALT) level greater than (>) 50 international units per liter (IU/L), at Screening;
- Had a Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) greater than or equal to (>=) 5, at Screening;
- Had a Body Mass Index z-score (BMI z-score) (also referred to as BMI-for-age percentile) >=85th percentile for age and gender at Screening;
- Had a Hemoglobin A1C (HbA1c) less than or equal (<=) to 8.5%. If the participants had Type 2 diabetes and is taking anti-diabetic therapy (e.g., metformin or insulin), treatment must had been started at least 3 months prior to Screening and the dose must had been stable for at least 3 months prior to Screening and should remain stable through Randomization;
- Sexually active female participants of childbearing potential must had agree to utilize a highly effective method of contraception per the Clinical Trial Facilitation Group Guidelines from Screening through 30 days after the last dose of study drug (1 month after the end of treatment), and agree to monthly pregnancy testing during the study up to and including end of study.
- Other inclusion criteria may apply
Who cannot join
- Had history of bariatric surgery or planned surgery during the study period;
- Had known history of heart disease;
- Had uncontrolled hypertension evidenced by sustained elevation in systolic blood pressure greater than140 mmHg or diastolic blood pressure greater than 90 mmHg despite treatment with antihypertensive therapy, prior to Randomization;
- Had a known history of Type 1 diabetes;
- Had a known history of acquired immunodeficiency syndrome or positive screening for human immunodeficiency virus antibodies at Screening Visit;
- Had a documented weight loss of more than 5% during the 6-month period prior to Randomization;
Show all 29Show fewer
- Had a history of renal disease defined as an estimated glomerular filtration rate (eGFR) less than 90 mL/min/1.73 m^2 using the Schwartz Bedside GFR Calculator for Children or present at Screening Visit;
- History of, significant alcohol consumption or inability to reliably quantify alcohol intake, and/or use of illicit drugs.
- Had clinical and/or historical evidence of cirrhosis, included by not limited to:
- Abnormal hemoglobin (with the exception of females with a documented history of a low hemoglobin during menstruation);
- White blood cell count less than 3,500 cells/mm^3 of blood;
- Platelet count less than150,000 cells/mm^3 of blood;
- Direct bilirubin greater than 0.3 mg/dL;
- Total bilirubin greater than 1.3 mg/dL unless the patient has a diagnosis of Gilbert disease in which case direct bilirubin, reticulocyte count and haemoglobin must be normal;
- Serum albumin less than 3.5 g/dL;
- International normalized ratio (INR) greater than 1.4;
- Has evidence of chronic liver disease other than NASH, defined by any one of the following:
- Biopsy consistent with histological evidence of autoimmune hepatitis;
- Serum hepatitis A antibody positive;
- Serum hepatitis B surface antigen positive;
- Serum hepatitis C antibody positive;
- Serum hepatitis E antibody positive;
- History of or current positive Anti-Mitochondrial Antibody Test;
- Known or current Iron/total iron binding capacity ratio (transferrin saturation) greater than 45% with histological evidence of iron overload;
- Known or current Alpha-1-antitrypsin phenotype/genotype ZZ or SZ;
- Diagnosis of Wilson's disease;
- Had AST and/or ALT greater than 8 fold the upper limit of normal;
- Was pregnant, lactating or is planning to become pregnant during the study;
- Other exclusion criteria may apply
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Columbia University
New York, New York, 10032
University of California
San Diego, California, 92103
About this study
Official title: An Open Label, Randomized, Multicenter Study to Assess the Pharmacokinetic and Pharmacodynamic Profile and the Safety and Tolerability of Two Dose Levels of Elafibranor (80 mg and 120 mg) in Children and Adolescents, 8 to 17 Years of Age, With Nonalcoholic Steatohepatitis (NASH)
The study was being conducted in order to assess the pharmacokinetics and the safety of elafibranor following once daily administration of two dose levels of elafibranor (80 milligrams [mg] and 120mg) during 3 months in children and adolescent population (8 to 17 years of age) with non alcoholic steatohepatitis (NASH).
- Conditions
- Non Alcoholic Steatohepatitis
- Being tested
- Elafibranor 80mg, Elafibranor 120mg
- Keywords
- Pediatric, Pharmacokinetics
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Elafibranor 80mgDrug
Also called GFT505
Once daily oral intake of elafibranor 80 mg during 3 months
Elafibranor 120mgDrug
Also called GFT505
Once daily oral intake of elafibranor 120 mg during 3 months
| Study group | Role | What they receive |
|---|---|---|
| Elafibranor 80 mg | Experimental | Participants received Elafibranor 80 mg tablet orally once daily for 12 weeks. Receives: Drug: Elafibranor 80mg |
| Elafibranor 120 mg | Experimental | Participants received Elafibranor 120 mg tablet orally once daily for 12 weeks. Receives: Drug: Elafibranor 120mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Elafibranor and Its Active Metabolite (GFT1007)
Cmax was defined as maximum observed plasma concentration.
Measured: Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration
Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of Elafibranor and Active Metabolite (GFT1007)
Tmax was defined as time to reach maximum observed plasma concentration.
Measured: Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration
Pharmacokinetics: Area Under The Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Elafibranor and Active Metabolite (GFT1007)
AUC0-24 defined as the area under the plasma concentration versus time curve of the study drug from time 0 to 24 hours.
Measured: Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration
Pharmacokinetics: Terminal Elimination Half-life ( t½) of Elafibranor and Active Metabolite (GFT1007)
Plasma t1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.
Measured: Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration
Pharmacokinetics: Plasma Trough Concentrations (Ctrough) of Elafibranor and Active Metabolite (GFT1007)
Ctrough was defined as the plasma concentration of study drug observed just before treatment administration during repeated dosing.
Measured: Pre-dose on Day 1 and 29
Secondary outcomes (34)
Pharmacodynamics (PD) - Liver Markers: Change From Baseline in Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), and Alkaline Phosphatase (ALP) at Days 15, 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis. Normal range at screening: AST: 0 - 39 international units per liter (IU/L), ALT: 5 - 30 IU/L, GGT: 2 - 24 IU/L, and ALP: 74 - 390 IU/L.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Other Liver Markers: Change From Baseline in Adiponectin at Days 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.
Measured: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Other Liver Markers: Change From Baseline in Cytokeratin 18 (CK-18)/M65 and CK-18/M30 at Days 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.
Measured: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Other Liver Markers: Change From Baseline in Ferritin at Days 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.
Measured: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Other Liver Markers: Change From Baseline in Fibroblast Growth Factor 19 and Fibroblast Growth Factor 21 at Days 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.
Measured: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Other Liver Markers: Change From Baseline in Hyaluronic Acid, Procollagen 3 N-Terminal Propeptide (PIIINP) and Tissue Inhibitor of Metalloproteinase 1 (TIMP1) at Days 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.
Measured: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Other Liver Markers: Change From Baseline in Alpha-2 Macroglobulin at Days 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.
Measured: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Glucose Homeostasis Markers: Change From Baseline in Fasting Plasma Glucose (FPG) at Days 15, 29, 57, 85, and 113
Blood samples were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Glucose Homeostasis Markers: Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Days 15, 29, 57, 85, and 113
HOMA IR measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR = fasting plasma insulin (micro international units per milliliter [mcIU/mL]) * fasting plasma glucose (mmol/L) / 22.5. A higher value indicates a greater insulin resistance. Blood samples were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Glucose Homeostasis Markers: Change From Baseline in Fasting Insulin at Days 15, 29, 57, 85, and 113
Blood samples were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1. Here, "mIU/L" was abbreviated as "milli-international unit per liter".
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Total Cholesterol (TC) at Days 15, 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Non High-density Lipoprotein Cholesterol (Non-HDL-C) at Days 15, 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum High-density Lipoprotein Cholesterol (HDL-C) at Days 15, 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Low-density Lipoprotein (LDL-C) at Days 15, 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Triglycerides at Days 15, 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Calculated Very Low-density Lipoprotein Cholesterol (VLDL-C) at Days 15, 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Apolipoprotein A-1 at Days 15, 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Apolipoprotein B at Days 15, 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Change From Baseline in Body Weight at Days 15, 29, 57, 85, and 113
Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Change From Baseline in Body Mass Index (BMI) Z-Score at Days 15, 29, 57, 85, and 113
The BMI for a given age (in years) and gender (male) was converted to an exact z-score. Given a participant's age, sex, BMI, and an appropriate reference standard, a BMI Z-score was determined. BMI Z-score >=85th percentile was considered as overweight. Z-score was a statistical measure to describe whether a mean was above or below the standard. A Z-score of 0 was equal to the mean and is considered normal. Negative numbers indicate values lower than the mean and positive numbers indicate values higher than the mean. Negative values are indicative of decrease in BMI (weight loss) and positive values are indicative of increase in BMI. Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Change From Baseline in Waist Circumference at Days 15, 29, 57, 85, and 113
Waist circumference (in centimeters [cm]) was measured at the midpoint between the lower margin of the least palpable rib and the top of the iliac crest. Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Fibrinogen at Days 29, 57, 85, and 113
Blood samples to assess fibrinogen levels were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Haptoglobin at Days 29, 57, 85, and 113
Blood samples to assess Haptoglobin level were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Interleukin-6 at Days 29, 57, 85, and 113
Blood samples to assess Interleukin-6 level were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Tumor Necrosis Factor Alpha at Days 29, 57, 85, and 113
Blood samples to assess Necrosis Factor Alpha level were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Plasminogen Activator Inhibitor-1 at Days 29, 57, 85, and 113
Blood samples to assess plasminogen activator inhibitor-1 level were taken after minimum 10 hours of fasting. Baseline was defined as the last measurement before first intake of study treatment on Day 1. Here, "IU/mL" was abbreviated as International units per milliliter.
Measured: Baseline (Day 1), Day 29, 57, 85, and 113
Pharmacodynamics - Change From Baseline in Pediatric Quality of Life (PedsQL™) (Version 4.0) Generic Core Scales at Day 85
The child, adolescent and parent/legal guardian PedsQL™ (Version 4.0) generic core scales was used to measure health-related quality of life (HRQOL). The response information was completed by the participant and by a parent/legal guardian individually. It consisted of 23 item questionnaire encompassing 4 core scale domains: Physical Functioning (8 items); Emotional Functioning (5 items); Social Functioning (5 items); and School Functioning (5 items). Items were scored on a 5 point Likert-type response scale: 0=never a problem to 1=almost never a problem; 2=sometimes a problem; 3=often a problem; and 4=almost always a problem). Once scored, items were reverse scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), where higher scores indicated better HRQOL. Total Scale Score was the sum of all the items over the number of items answered on all the Scales. Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Day 85
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) was any untoward medical in a participant or clinical investigation patient administered a pharmaceutical (investigational) product and which does not necessarily have to have a causal relationship with this treatment. A Serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization/prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was another medically important condition. TEAEs were defined as AEs that started prior to first study drug dose and that worsened after, and the AEs that started on or after first study drug dose. TEAEs: Serious and non-serious AEs.
Measured: From Screening visit (signature of informed consent) up to last dose of study drug + 30 days (i.e., up to Day 113)
Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Measurement
ECG measurements were taken with the participants in resting position for at least 10 minutes. The investigator determined whether abnormal assessment results were clinically significant or not. The number of participants with abnormal clinically significant ECG findings were reported. Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Day 85
Number of Participants With Abnormal Clinical Chemistry Parameters
Fasting blood samples (collected after 10 hours fasting) were used to assess the following clinical chemistry parameters: creatinine, glomerular filtration rate, creatinine clearance, total proteins, albumin, electrolytes (sodium, potassium, chloride, calcium), uric acid, urea nitrogen, urea, creatine phosphokinase (CPK), AST, ALT, GGT, ALP, total and conjugated bilirubin, high sensitivity C-reactive protein, fasting plasma glucose, fasting insulin, HOMA-IR, fructosamine, C-peptide, free fatty acids, glycated hemoglobin A1c, cystatin C. Abnormal clinical chemistry values were classified based on reference range: lower limit of normality (LLN); normal (>= LLN and <= upper limit of normality [ULN]); > ULN and <3 ULN; >=3 ULN and <5 ULN and >=5 ULN. Only the parameters for which at least one value of abnormality were reported and presented in this outcome measure.
Measured: At Day 85 (i.e., end of treatment)
Number of Participants With Abnormal Hematology and Coagulation Parameters
Fasting blood samples (collected after 10 hours fasting) were used to assess the following hematology and coagulation parameters: hemoglobin, hematocrit, red blood cells (RBC), white blood cells (WBC), neutrophils, eosinophils, basophils, lymphocytes, monocytes, platelets, prothrombin time (PT) and international normalized ratio (INR). Hematology and coagulation values were classified based on the reference range: LLN; normal (>= LLN and <= ULN); > ULN and <3 ULN; >=3 ULN and <5 ULN and >=5 ULN.
Measured: At Day 85 (i.e., end of treatment)
Number of Participants With Abnormal Urinalysis Parameters
Blood samples were collected to assess the following urinalysis parameters: alpha-1 macroglobulin, N-acetyl glucosamide, neutrophil gelatinase-associated lipocalin, albumin, and creatinine. Abnormal urinalysis values were classified based on the reference range: LLN; normal (>= LLN and <= ULN); > ULN and <3 ULN; >=3 ULN and <5 ULN and >=5 ULN.
Measured: At Day 85 (i.e., end of treatment)
Number of Participants With Abnormal Vital Signs
Vital signs were taken before any invasive procedures. Following vital signs were assessed: systolic blood pressure, diastolic blood pressure, heart rate. Abnormal vita signs was defined as any abnormal findings in the vital sign parameters and were categorized as 'abnormal, not clinically significant (NCS)' and 'abnormal, clinically significant (CS)'.
Measured: At Day 85 (i.e., end of treatment)
Number of Participants With Clinically Significant Abnormalities in Physical Examination at Baseline, Days 15, 29, 57, 85, and 113
Physical examination findings were collected according to pre-defined body systems: general appearance; skin; eyes; ears; nose; throat; neck and thyroid; lungs; heart; upper/lower extremities; lymph nodes; abdomen; musculoskeletal system; basic neurological assessment. Additional systems were evaluated as needed. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care. Participants with at least one clinically significant abnormality in physical examination were reported and presented in this outcome measure. Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Measured: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2019
- Study start25 Jun 2019
- Primary completion16 Jun 2020
- Study completion16 Jun 2020
Why it stopped: Due to lack of efficacy (but not due to safety) in a Phase 3 trial of elafibranor in adult participants with NASH and fibrosis, this study in pediatric NASH was prematurely terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non Alcoholic SteatohepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genfit
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Carol Addy, MD MMSc, Study director, Genfit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03883607
- Sponsor's protocol ID
- GFT505E-218-1
- Other IDs
- 2019-003400-12, 2019
- Status last verified
- Sep 2021
- First submitted
- 13 Mar 2019
- Last updated
- 28 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Goyal NP, Mencin A, Newton KP, Durelle J, Carrier C, Ugalde-Nicalo P, Noel B, Mouton J, Vargas D, Magrez D, Tadde B, Birman P, Best BM, Addy C, Schwimmer JB. An Open Label, Randomized, Multicenter Study of Elafibranor in Children With Nonalcoholic Steatohepatitis. J Pediatr Gastroenterol Nutr. 2023 Aug 1;77(2):160-165. doi: 10.1097/MPG.0000000000003796. Epub 2023 Apr 21.
PubMed 37084342
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Randomized, Multicenter Study to Assess the Pharmacokinetic and Pharmacodynamic Profile and the Safety and Tolerability of Two Dose Levels of Elafibranor (80 mg and 120 mg) in Children and Adolescents, 8 to 17 Years of Age, With Nonalcoholic Steatohepatitis (NASH)
- ClinicalTrials.gov ID
- NCT03883607
- Acronym / sponsor ID
- GFT505E-218-1
- Conditions
- Non Alcoholic Steatohepatitis
- Keywords
- Pediatric, Pharmacokinetics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to lack of efficacy (but not due to safety) in a Phase 3 trial of elafibranor in adult participants with NASH and fibrosis, this study in pediatric NASH was prematurely terminated
- Enrolment
- 10 participants (actual)
- Lead sponsor
- GenfitIndustry (pharma, biotech, devices)
- Study start
- 25 Jun 2019 (actual)
- Primary completion
- 16 Jun 2020 (actual)
- Study completion
- 16 Jun 2020 (actual)
- First posted
- 21 Mar 2019 (actual)
- Results
- Posted 28 Oct 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study was being conducted in order to assess the pharmacokinetics and the safety of elafibranor following once daily administration of two dose levels of elafibranor (80 milligrams [mg] and 120mg) during 3 months in children and adolescent population (8 to 17 years of age) with non alcoholic steatohepatitis (NASH).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Elafibranor 80 mg | Experimental | Drug: Elafibranor 80mgParticipants received Elafibranor 80 mg tablet orally once daily for 12 weeks. |
| Elafibranor 120 mg | Experimental | Drug: Elafibranor 120mgParticipants received Elafibranor 120 mg tablet orally once daily for 12 weeks. |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Was male or female between 8 and 17 years of age (inclusive) at the time of Screening Visit (when consent for study participation is given) and at the time of Randomization;
- Diagnosis of NASH confirmed by histological evaluation (with or without fibrosis) from a liver biopsy obtained within 24 months prior to Randomization;
- Had an alanine aminotransferase (ALT) level greater than (>) 50 international units per liter (IU/L), at Screening;
- Had a Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) greater than or equal to (>=) 5, at Screening;
- Had a Body Mass Index z-score (BMI z-score) (also referred to as BMI-for-age percentile) >=85th percentile for age and gender at Screening;
Key exclusion criteria (29 listed)
- Had history of bariatric surgery or planned surgery during the study period;
- Had known history of heart disease;
- Had uncontrolled hypertension evidenced by sustained elevation in systolic blood pressure greater than140 mmHg or diastolic blood pressure greater than 90 mmHg despite treatment with antihypertensive therapy, prior to Randomization;
- Had a known history of Type 1 diabetes;
- Had a known history of acquired immunodeficiency syndrome or positive screening for human immunodeficiency virus antibodies at Screening Visit;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Elafibranor 80mgAlso: GFT505Once daily oral intake of elafibranor 80 mg during 3 months | Drug | Elafibranor 80 mg |
| Elafibranor 120mgAlso: GFT505Once daily oral intake of elafibranor 120 mg during 3 months | Drug | Elafibranor 120 mg |
Primary outcome
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Elafibranor and Its Active Metabolite (GFT1007)
Time frame: Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration
Cmax was defined as maximum observed plasma concentration.
Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of Elafibranor and Active Metabolite (GFT1007)
Time frame: Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration
Tmax was defined as time to reach maximum observed plasma concentration.
Pharmacokinetics: Area Under The Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Elafibranor and Active Metabolite (GFT1007)
Time frame: Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration
AUC0-24 defined as the area under the plasma concentration versus time curve of the study drug from time 0 to 24 hours.
Pharmacokinetics: Terminal Elimination Half-life ( t½) of Elafibranor and Active Metabolite (GFT1007)
Time frame: Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration
Plasma t1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.
Pharmacokinetics: Plasma Trough Concentrations (Ctrough) of Elafibranor and Active Metabolite (GFT1007)
Time frame: Pre-dose on Day 1 and 29
Ctrough was defined as the plasma concentration of study drug observed just before treatment administration during repeated dosing.
34 secondary outcomes
Pharmacodynamics (PD) - Liver Markers: Change From Baseline in Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), and Alkaline Phosphatase (ALP) at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Other Liver Markers: Change From Baseline in Adiponectin at Days 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Other Liver Markers: Change From Baseline in Cytokeratin 18 (CK-18)/M65 and CK-18/M30 at Days 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Other Liver Markers: Change From Baseline in Ferritin at Days 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Other Liver Markers: Change From Baseline in Fibroblast Growth Factor 19 and Fibroblast Growth Factor 21 at Days 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Other Liver Markers: Change From Baseline in Hyaluronic Acid, Procollagen 3 N-Terminal Propeptide (PIIINP) and Tissue Inhibitor of Metalloproteinase 1 (TIMP1) at Days 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Other Liver Markers: Change From Baseline in Alpha-2 Macroglobulin at Days 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Glucose Homeostasis Markers: Change From Baseline in Fasting Plasma Glucose (FPG) at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Glucose Homeostasis Markers: Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Glucose Homeostasis Markers: Change From Baseline in Fasting Insulin at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Total Cholesterol (TC) at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Non High-density Lipoprotein Cholesterol (Non-HDL-C) at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum High-density Lipoprotein Cholesterol (HDL-C) at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Low-density Lipoprotein (LDL-C) at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Triglycerides at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Calculated Very Low-density Lipoprotein Cholesterol (VLDL-C) at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Apolipoprotein A-1 at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Apolipoprotein B at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Change From Baseline in Body Weight at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Change From Baseline in Body Mass Index (BMI) Z-Score at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Change From Baseline in Waist Circumference at Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Fibrinogen at Days 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Haptoglobin at Days 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Interleukin-6 at Days 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Tumor Necrosis Factor Alpha at Days 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 29, 57, 85, and 113
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Plasminogen Activator Inhibitor-1 at Days 29, 57, 85, and 113
Time frame: Baseline (Day 1), Day 29, 57, 85, and 113
Pharmacodynamics - Change From Baseline in Pediatric Quality of Life (PedsQL™) (Version 4.0) Generic Core Scales at Day 85
Time frame: Baseline (Day 1), Day 85
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: From Screening visit (signature of informed consent) up to last dose of study drug + 30 days (i.e., up to Day 113)
Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Measurement
Time frame: Baseline (Day 1), Day 85
Number of Participants With Abnormal Clinical Chemistry Parameters
Time frame: At Day 85 (i.e., end of treatment)
Number of Participants With Abnormal Hematology and Coagulation Parameters
Time frame: At Day 85 (i.e., end of treatment)
Number of Participants With Abnormal Urinalysis Parameters
Time frame: At Day 85 (i.e., end of treatment)
Number of Participants With Abnormal Vital Signs
Time frame: At Day 85 (i.e., end of treatment)
Number of Participants With Clinically Significant Abnormalities in Physical Examination at Baseline, Days 15, 29, 57, 85, and 113
Time frame: Baseline (Day 1), Days 15, 29, 57, 85, and 113
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37084342Goyal NP, Mencin A, Newton KP, Durelle J, Carrier C, Ugalde-Nicalo P, Noel B, Mouton J, Vargas D, Magrez D, Tadde B, Birman P, Best BM, Addy C, Schwimmer JB. An Open Label, Randomized, Multicenter Study of Elafibranor in Children With Nonalcoholic Steatohepatitis. J Pediatr Gastroenterol Nutr. 2023 Aug 1;77(2):160-165. doi: 10.1097/MPG.0000000000003796. Epub 2023 Apr 21.
- Individual participant dataSharing planned: Undecided
Related trials for Non Alcoholic Steatohepatitis
Not yet recruiting
Efficacy of Carnitine Complex in Improving Hepatic Steatosis in Potential Liver Donors
Hepatic Steatosis, Fatty Liver
RecruitingPhase 3
A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
NASH With Fibrosis, MASH With Fibrosis
Recruiting
NAFLD Clinical Care Pathway
NAFLD, MASLD
RecruitingPhase 3
Trial to Evaluate ALN-CIDEB in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease, MASLD
RecruitingPhase 1
A Study of Efimosfermin Alfa in Adults With Hepatic Impairment
Non-alcoholic Fatty Liver Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carol Addy, MD MMSc study director
Genfit
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Elafibranor 80mg and Elafibranor 120mg in people with Non Alcoholic Steatohepatitis, run by Genfit at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Elafibranor and Its Active Metabolite (GFT1007) (time frame: Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03883607, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2021.