Elafibranor, PK and Safety in Children and Adolescents 8 to 17 Years of Age With Non Alcoholic Steatohepatitis (NASH)

• Sponsor: Genfit (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03883607
• Collaborator: (none)
• Enrollment: 10
• Locations: 2
• Arms: 2
• Actual Duration (Months): 11.7
• Patients Per Site: 5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Non Alcoholic Steatohepatitis	Drug: Elafibranor 80mg; Drug: Elafibranor 120mg	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: Jun 25, 2019
• Actual Primary Completion Date: Jun 16, 2020
• Actual Study Completion Date: Jun 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Elafibranor 80 mg Participants received Elafibranor 80 mg tablet orally once daily for 12 weeks.	Drug: Elafibranor 80mg; Once daily oral intake of elafibranor 80 mg during 3 months; Other Names: GFT505
Experimental: Elafibranor 120 mg Participants received Elafibranor 120 mg tablet orally once daily for 12 weeks.	Drug: Elafibranor 120mg; Once daily oral intake of elafibranor 120 mg during 3 months; Other Names: GFT505

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Elafibranor and Its Active Metabolite (GFT1007) [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.

2. Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of Elafibranor and Active Metabolite (GFT1007) [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.

3. Pharmacokinetics: Area Under The Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Elafibranor and Active Metabolite (GFT1007) [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.

4. Pharmacokinetics: Terminal Elimination Half-life ( t½) of Elafibranor and Active Metabolite (GFT1007) [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.

5. Pharmacokinetics: Plasma Trough Concentrations (Ctrough) of Elafibranor and Active Metabolite (GFT1007) [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.

Secondary Outcome Measures

1. 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 (Day 1), 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.

2. Pharmacodynamics - Other Liver Markers: Change From Baseline in Adiponectin at Days 29, 57, 85, and 113 [Baseline (Day 1), 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.

3. 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 (Day 1), 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.

4. Pharmacodynamics - Other Liver Markers: Change From Baseline in Ferritin at Days 29, 57, 85, and 113 [Baseline (Day 1), 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.

5. 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 (Day 1), 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.

6. 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 (Day 1), 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.

7. Pharmacodynamics - Other Liver Markers: Change From Baseline in Alpha-2 Macroglobulin at Days 29, 57, 85, and 113 [Baseline (Day 1), 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.

8. Pharmacodynamics - Glucose Homeostasis Markers: Change From Baseline in Fasting Plasma Glucose (FPG) at Days 15, 29, 57, 85, and 113 [Baseline (Day 1), 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.

9. Pharmacodynamics - Glucose Homeostasis Markers: Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Days 15, 29, 57, 85, and 113 [Baseline (Day 1), 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.

10. Pharmacodynamics - Glucose Homeostasis Markers: Change From Baseline in Fasting Insulin at Days 15, 29, 57, 85, and 113 [Baseline (Day 1), 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".

11. Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Total Cholesterol (TC) at Days 15, 29, 57, 85, and 113 [Baseline (Day 1), Days 15, 29, 57, 85, and 113]

    Baseline was defined as the last measurement before first intake of study treatment on Day 1.

12. 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 (Day 1), Days 15, 29, 57, 85, and 113]

    Baseline was defined as the last measurement before first intake of study treatment on Day 1.

13. Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum High-density Lipoprotein Cholesterol (HDL-C) at Days 15, 29, 57, 85, and 113 [Baseline (Day 1), Days 15, 29, 57, 85, and 113]

    Baseline was defined as the last measurement before first intake of study treatment on Day 1.

14. Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Low-density Lipoprotein (LDL-C) at Days 15, 29, 57, 85, and 113 [Baseline (Day 1), Days 15, 29, 57, 85, and 113]

    Baseline was defined as the last measurement before first intake of study treatment on Day 1.

15. Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Triglycerides at Days 15, 29, 57, 85, and 113 [Baseline (Day 1), Days 15, 29, 57, 85, and 113]

    Baseline was defined as the last measurement before first intake of study treatment on Day 1.

16. 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 (Day 1), Days 15, 29, 57, 85, and 113]

    Baseline was defined as the last measurement before first intake of study treatment on Day 1.

17. Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Apolipoprotein A-1 at Days 15, 29, 57, 85, and 113 [Baseline (Day 1), Days 15, 29, 57, 85, and 113]

    Baseline was defined as the last measurement before first intake of study treatment on Day 1.

18. Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Apolipoprotein B at Days 15, 29, 57, 85, and 113 [Baseline (Day 1), Days 15, 29, 57, 85, and 113]

    Baseline was defined as the last measurement before first intake of study treatment on Day 1.

19. Pharmacodynamics - Change From Baseline in Body Weight at Days 15, 29, 57, 85, and 113 [Baseline (Day 1), Days 15, 29, 57, 85, and 113]

    Baseline was defined as the last measurement before first intake of study treatment on Day 1.

20. Pharmacodynamics - Change From Baseline in Body Mass Index (BMI) Z-Score at Days 15, 29, 57, 85, and 113 [Baseline (Day 1), 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.

21. Pharmacodynamics - Change From Baseline in Waist Circumference at Days 15, 29, 57, 85, and 113 [Baseline (Day 1), 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.

22. Pharmacodynamics - Inflammatory Marker: Change From Baseline in Fibrinogen at Days 29, 57, 85, and 113 [Baseline (Day 1), 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.

23. Pharmacodynamics - Inflammatory Marker: Change From Baseline in Haptoglobin at Days 29, 57, 85, and 113 [Baseline (Day 1), 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.

24. Pharmacodynamics - Inflammatory Marker: Change From Baseline in Interleukin-6 at Days 29, 57, 85, and 113 [Baseline (Day 1), 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.

25. Pharmacodynamics - Inflammatory Marker: Change From Baseline in Tumor Necrosis Factor Alpha at Days 29, 57, 85, and 113 [Baseline (Day 1), 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.

26. Pharmacodynamics - Inflammatory Marker: Change From Baseline in Plasminogen Activator Inhibitor-1 at Days 29, 57, 85, and 113 [Baseline (Day 1), Day 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.

27. Pharmacodynamics - Change From Baseline in Pediatric Quality of Life (PedsQL™) (Version 4.0) Generic Core Scales at Day 85 [Baseline (Day 1), 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.

28. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs [From Screening visit (signature of informed consent) up to last dose of study drug + 30 days (i.e., up to Day 113)]

    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.

29. Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Measurement [Baseline (Day 1), Day 85]

    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.

30. Number of Participants With Abnormal Clinical Chemistry Parameters [At Day 85 (i.e., end of treatment)]

    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.

31. Number of Participants With Abnormal Hematology and Coagulation Parameters [At Day 85 (i.e., end of treatment)]

    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.

32. Number of Participants With Abnormal Urinalysis Parameters [At Day 85 (i.e., end of treatment)]

    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.

33. Number of Participants With Abnormal Vital Signs [At Day 85 (i.e., end of treatment)]

    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)'.

34. Number of Participants With Clinically Significant Abnormalities in Physical Examination at Baseline, Days 15, 29, 57, 85, and 113 [Baseline (Day 1), 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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;

• 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:

1. Abnormal hemoglobin (with the exception of females with a documented history of a low hemoglobin during menstruation);

2. White blood cell count less than 3,500 cells/mm^3 of blood;

3. Platelet count less than150,000 cells/mm^3 of blood;

4. Direct bilirubin greater than 0.3 mg/dL;

5. 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;

6. Serum albumin less than 3.5 g/dL;

7. International normalized ratio (INR) greater than 1.4;

• Has evidence of chronic liver disease other than NASH, defined by any one of the following:

1. Biopsy consistent with histological evidence of autoimmune hepatitis;

2. Serum hepatitis A antibody positive;

3. Serum hepatitis B surface antigen positive;

4. Serum hepatitis C antibody positive;

5. Serum hepatitis E antibody positive;

6. History of or current positive Anti-Mitochondrial Antibody Test;

7. Known or current Iron/total iron binding capacity ratio (transferrin saturation) greater than 45% with histological evidence of iron overload;

8. Known or current Alpha-1-antitrypsin phenotype/genotype ZZ or SZ;

9. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California	San Diego	California	United States	92103
2	Columbia University	New York	New York	United States	10032

Sponsors and Collaborators

• Genfit

Investigators

• Study Director: Carol Addy, MD MMSc, Genfit

Study Documents (Full-Text)

• Study Protocol - Apr 20, 2020
• Statistical Analysis Plan - Aug 20, 2020

More Information

Publications

None provided.

• Responsible Party: Genfit
• ClinicalTrials.gov Identifier: NCT03883607
• Other Study ID Numbers: GFT505E-218-1; 2019-003400-12
• First Posted: Mar 21, 2019
• Last Update Posted: Oct 28, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Genfit: Pediatric; Pharmacokinetics
• Additional relevant MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease

Study Results

Participant Flow

Recruitment Details

The study was conducted at 2 centers in the United Sates from 25 June 2019 and 16 June 2020. A total of 27 participants were screened, of which 10 participants were enrolled and randomized (1:1 ratio) to receive elafibranor 80 milligrams (mg)/120 mg sequentially. A total of 17 participants failed screening mainly due to not meeting eligibility criteria.

Pre-assignment Detail

Screening was performed up to 4 weeks before study drug administered. Randomization was stratified by age (Cohort 1: greater than or equal to [>=] 12 to less than or equal to [<=] 17 years of age and Cohort 2: >=8 to <=11 years of age) and participant's historical fibrosis severity stage (stratum 1: fibrosis stage 0 to 1 and stratum 2: fibrosis stage 2 to 3). Due to lack of efficacy study was prematurely terminated, only Cohort 1 participants were involved in this study.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Period Title: Overall Study
STARTED	5	5
COMPLETED	5	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg	Total
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.	Total of all reporting groups
Overall Participants	5	5	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.52 (2.23)	15.70 (2.31)	15.11 (2.23)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	5 100%	5 100%	10 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 80%	5 100%	9 90%
Not Hispanic or Latino	1 20%	0 0%	1 10%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	2 40%	3 60%	5 50%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 60%	2 40%	5 50%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Elafibranor and Its Active Metabolite (GFT1007)
Description	Cmax was defined as maximum observed plasma concentration.
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

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population that included all participants who had received at least 1 dose of the study drug, did not had protocol deviations or adverse events (AEs) that significantly affected the PK, and had at least 1 post-dose PK sample.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Elafibranor	385.216 (218.646)	658.054 (403.201)
GFT1007	2367.620 (1088.123)	2875.280 (1443.324)

2. Primary Outcome

Title	Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of Elafibranor and Active Metabolite (GFT1007)
Description	Tmax was defined as time to reach maximum observed plasma concentration.
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

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Elafibranor	1.50	1.00
GFT1007	2.00	1.50

3. Primary Outcome

Title	Pharmacokinetics: Area Under The Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Elafibranor and Active Metabolite (GFT1007)
Description	AUC0-24 defined as the area under the plasma concentration versus time curve of the study drug from time 0 to 24 hours.
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

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Elafibranor	973.301 (311.803)	1457.728 (724.018)
GFT1007	10011.405 (3575.220)	10532.930 (3257.220)

4. Primary Outcome

Title	Pharmacokinetics: Terminal Elimination Half-life ( t½) of Elafibranor and Active Metabolite (GFT1007)
Description	Plasma t1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.
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

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific categories.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Elafibranor	34.170 (NA)	37.620 (15.473)
GFT1007	9.572 (5.592)	6.682 (1.120)

5. Primary Outcome

Title	Pharmacokinetics: Plasma Trough Concentrations (Ctrough) of Elafibranor and Active Metabolite (GFT1007)
Description	Ctrough was defined as the plasma concentration of study drug observed just before treatment administration during repeated dosing.
Time Frame	Pre-dose on Day 1 and 29

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Elafibranor	14.904 (3.516)	29.035 (15.087)
GFT1007	97.771 (49.636)	55.243 (27.769)

6. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific categories.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
ALT: Day 15	4.2 (21.7)	-13.8 (25.0)
ALT: Day 29	-0.2 (35.9)	-27.6 (18.4)
ALT: Day 57	0.2 (27.3)	-30.8 (16.5)
ALT: Day 85	17.8 (56.6)	-34.6 (25.6)
ALT: Day 113	37.3 (46.9)	-28.0 (22.2)
AST: Day 15	4.0 (16.0)	0.8 (9.5)
AST: Day 29	4.0 (16.3)	-4.0 (9.5)
AST: Day 57	1.0 (6.1)	-5.8 (4.1)
AST: Day 85	7.4 (15.3)	-8.2 (8.3)
AST: Day 113	9.3 (8.4)	-7.8 (8.7)
GGT: Day 15	-9.2 (6.8)	-8.8 (4.4)
GGT: Day 29	-15.6 (9.9)	-16.0 (5.9)
GGT: Day 57	-1.0 (20.7)	-15.6 (9.1)
GGT: Day 85	11.2 (39.1)	-16.2 (9.9)
GGT: Day 113	45.3 (43.8)	-9.5 (6.6)
ALP: Day 15	-4.6 (23.1)	-18.0 (11.2)
ALP: Day 29	-24.8 (28.4)	-14.6 (8.1)
ALP: Day 57	-28.2 (36.5)	-18.4 (8.2)
ALP: Day 85	-32.6 (51.5)	-25.0 (12.4)
ALP: Day 113	-7.8 (45.4)	-16.8 (10.2)

7. Secondary Outcome

Title	Pharmacodynamics - Other Liver Markers: Change From Baseline in Adiponectin at Days 29, 57, 85, and 113
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.
Time Frame	Baseline (Day 1), Days 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 29	0.2410 (0.3729)	0.2112 (1.0304)
Day 57	0.5780 (1.0530)	-0.2752 (1.0022)
Day 85	0.3372 (1.4844)	-0.0590 (1.0476)
Day 113	-0.4663 (0.8972)	0.0322 (1.0588)

8. Secondary Outcome

Title	Pharmacodynamics - Other Liver Markers: Change From Baseline in Cytokeratin 18 (CK-18)/M65 and CK-18/M30 at Days 29, 57, 85, and 113
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.
Time Frame	Baseline (Day 1), Days 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific categories.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
CK-18/M65: Day 29	39.412 (346.370)	-70.902 (121.905)
CK-18/M65: Day 57	-30.302 (326.632)	-60.578 (186.165)
CK-18/M65: Day 85	-2.320 (231.775)	-122.070 (265.059)
CK-18/M65: Day 113	235.205 (290.846)	-188.638 (244.324)
CK-18/M30: Day 29	-24.282 (374.146)	-68.896 (96.850)
CK-18/M30: Day 57	7.530 (445.509)	-20.074 (219.782)
CK-18/M30: Day 85	-54.988 (315.261)	-81.492 (271.506)
CK-18/M30: Day 113	146.412 (273.673)	-170.793 (235.722)

9. Secondary Outcome

Title	Pharmacodynamics - Other Liver Markers: Change From Baseline in Ferritin at Days 29, 57, 85, and 113
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.
Time Frame	Baseline (Day 1), Days 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 29	6.4 (12.0)	10.8 (25.9)
Day 57	19.4 (23.5)	3.6 (15.6)
Day 85	11.8 (16.6)	-4.0 (2.4)
Day 113	6.0 (5.7)	-12.8 (11.1)

10. Secondary Outcome

Title	Pharmacodynamics - Other Liver Markers: Change From Baseline in Fibroblast Growth Factor 19 and Fibroblast Growth Factor 21 at Days 29, 57, 85, and 113
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.
Time Frame	Baseline (Day 1), Days 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific categories.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Fibroblast Growth Factor 19: Day 29	-24.4 (80.6)	-42.8 (78.0)
Fibroblast Growth Factor 19: Day 57	-10.4 (51.2)	-18.8 (85.3)
Fibroblast Growth Factor 19: Day 85	28.4 (77.5)	-13.0 (100.6)
Fibroblast Growth Factor 19: Day 113	-7.8 (61.3)	-19.8 (35.3)
Fibroblast Growth Factor 21: Day 29	9.98 (91.38)	128.84 (171.50)
Fibroblast Growth Factor 21: Day 57	-36.36 (188.91)	195.94 (315.73)
Fibroblast Growth Factor 21: Day 85	120.68 (191.62)	81.56 (130.68)
Fibroblast Growth Factor 21: Day 113	3.50 (291.41)	56.35 (87.53)

11. Secondary Outcome

Title	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
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.
Time Frame	Baseline (Day 1), Days 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific categories.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Hyaluronic Acid: Day 29	-2.958 (11.689)	-8.800 (10.991)
Hyaluronic Acid: Day 57	-0.272 (9.228)	-3.654 (10.528)
Hyaluronic Acid: Day 85	4.408 (16.612)	-3.518 (15.130)
Hyaluronic Acid: Day 113	1.592 (16.445)	-0.422 (19.347)
Procollagen 3 N-Terminal Propeptide: Day 29	-3.018 (14.079)	-2.878 (3.138)
Procollagen 3 N-Terminal Propeptide: Day 57	1.730 (6.928)	-2.762 (3.242)
Procollagen 3 N-Terminal Propeptide: Day 85	-1.710 (6.730)	-0.470 (5.270)
Procollagen 3 N-Terminal Propeptide: Day 113	-7.015 (11.902)	-0.530 (3.701)
Tissue Inhibitor of Metalloproteinase 1: Day 29	-3.56 (25.38)	-8.52 (8.98)
Tissue Inhibitor of Metalloproteinase 1: Day 57	2.80 (15.35)	-26.20 (32.29)
Tissue Inhibitor of Metalloproteinase 1: Day 85	16.02 (24.84)	-26.26 (25.43)
Tissue Inhibitor of Metalloproteinase 1: Day 113	10.92 (21.58)	-31.35 (37.95)

12. Secondary Outcome

Title	Pharmacodynamics - Other Liver Markers: Change From Baseline in Alpha-2 Macroglobulin at Days 29, 57, 85, and 113
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1. Missing data were not imputed for the analysis.
Time Frame	Baseline (Day 1), Days 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 29	-0.098 (0.254)	-0.282 (0.133)
Day 57	0.124 (0.213)	-0.118 (0.064)
Day 85	-0.030 (0.328)	-0.204 (0.129)
Day 113	-0.105 (0.319)	-0.037 (0.157)

13. Secondary Outcome

Title	Pharmacodynamics - Glucose Homeostasis Markers: Change From Baseline in Fasting Plasma Glucose (FPG) at Days 15, 29, 57, 85, and 113
Description	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.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 15	0.22 (0.34)	0.22 (0.28)
Day 29	0.34 (0.61)	0.12 (0.47)
Day 57	0.18 (0.58)	0.10 (0.24)
Day 85	0.28 (0.63)	0.08 (0.45)
Day 113	0.58 (0.52)	0.17 (0.35)

14. Secondary Outcome

Title	Pharmacodynamics - Glucose Homeostasis Markers: Change From Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Days 15, 29, 57, 85, and 113
Description	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.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 15	10.720 (17.650)	-3.640 (5.215)
Day 29	16.498 (43.577)	-4.028 (6.512)
Day 57	4.958 (15.472)	-5.448 (3.572)
Day 85	3.742 (6.853)	-1.968 (7.112)
Day 113	13.323 (22.795)	-4.623 (6.883)

15. Secondary Outcome

Title	Pharmacodynamics - Glucose Homeostasis Markers: Change From Baseline in Fasting Insulin at Days 15, 29, 57, 85, and 113
Description	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".
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 15	30.88 (53.53)	-15.66 (20.92)
Day 29	40.12 (116.20)	-16.76 (24.12)
Day 57	12.42 (41.76)	-23.10 (12.58)
Day 85	9.70 (15.49)	-7.48 (26.76)
Day 113	34.15 (58.20)	-19.57 (25.56)

16. Secondary Outcome

Title	Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Total Cholesterol (TC) at Days 15, 29, 57, 85, and 113
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 15	-0.070 (0.440)	-0.328 (0.230)
Day 29	-0.356 (0.252)	-0.288 (0.347)
Day 57	0.380 (0.565)	-0.286 (0.129)
Day 85	0.298 (0.836)	-0.274 (0.306)
Day 113	0.665 (0.919)	0.105 (0.270)

17. Secondary Outcome

Title	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
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 15	-0.134 (0.414)	-0.348 (0.163)
Day 29	-0.324 (0.196)	-0.316 (0.432)
Day 57	0.368 (0.340)	-0.316 (0.194)
Day 85	0.156 (0.615)	-0.420 (0.290)
Day 113	0.605 (0.714)	-0.038 (0.229)

18. Secondary Outcome

Title	Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum High-density Lipoprotein Cholesterol (HDL-C) at Days 15, 29, 57, 85, and 113
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 15	0.060 (0.068)	0.020 (0.223)
Day 29	-0.032 (0.124)	0.032 (0.137)
Day 57	0.008 (0.228)	0.030 (0.168)
Day 85	0.138 (0.278)	0.150 (0.191)
Day 113	0.065 (0.259)	0.150 (0.047)

19. Secondary Outcome

Title	Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Low-density Lipoprotein (LDL-C) at Days 15, 29, 57, 85, and 113
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific time points.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 15	-0.224 (0.365)	-0.084 (0.213)
Day 29	-0.344 (0.184)	-0.076 (0.355)
Day 57	0.314 (0.355)	-0.038 (0.078)
Day 85	0.080 (0.686)	-0.184 (0.223)
Day 113	0.385 (0.691)	0.108 (0.134)

20. Secondary Outcome

Title	Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Triglycerides at Days 15, 29, 57, 85, and 113
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 15	0.200 (0.363)	-0.576 (0.442)
Day 29	0.042 (0.214)	-0.530 (0.385)
Day 57	0.124 (0.326)	-0.606 (0.384)
Day 85	0.170 (0.389)	-0.532 (0.399)
Day 113	0.485 (0.918)	-0.315 (0.353)

21. Secondary Outcome

Title	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
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 15	0.086 (0.172)	-0.270 (0.200)
Day 29	0.018 (0.103)	-0.244 (0.168)
Day 57	0.052 (0.140)	-0.282 (0.176)
Day 85	0.072 (0.168)	-0.240 (0.176)
Day 113	0.215 (0.419)	-0.153 (0.156)

22. Secondary Outcome

Title	Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Apolipoprotein A-1 at Days 15, 29, 57, 85, and 113
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 15	0.112 (0.129)	-0.058 (0.149)
Day 29	0.012 (0.139)	-0.058 (0.144)
Day 57	0.108 (0.211)	-0.060 (0.176)
Day 85	0.128 (0.268)	0.016 (0.160)
Day 113	0.103 (0.313)	0.048 (0.060)

23. Secondary Outcome

Title	Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Apolipoprotein B at Days 15, 29, 57, 85, and 113
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 15	-0.058 (0.064)	-0.082 (0.074)
Day 29	-0.098 (0.081)	-0.078 (0.097)
Day 57	0.066 (0.092)	-0.062 (0.086)
Day 85	0.020 (0.189)	-0.036 (0.090)
Day 113	0.117 (0.209)	-0.005 (0.135)

24. Secondary Outcome

Title	Pharmacodynamics - Change From Baseline in Body Weight at Days 15, 29, 57, 85, and 113
Description	Baseline was defined as the last measurement before first intake of study treatment on Day 1.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 15	-0.08 (3.03)	-0.92 (1.70)
Day 29	-0.32 (4.54)	-0.98 (2.06)
Day 57	0.73 (5.18)	-0.68 (3.27)
Day 85	1.54 (5.42)	0.24 (4.07)
Day 113	4.40 (3.05)	0.73 (4.63)

25. Secondary Outcome

Title	Pharmacodynamics - Change From Baseline in Body Mass Index (BMI) Z-Score at Days 15, 29, 57, 85, and 113
Description	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.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 15	-0.064 (0.146)	-0.054 (0.095)
Day 29	-0.091 (0.247)	-0.054 (0.110)
Day 57	-0.108 (0.284)	-0.058 (0.162)
Day 85	-0.074 (0.290)	-0.026 (0.197)
Day 113	0.068 (0.116)	0.022 (0.247)

26. Secondary Outcome

Title	Pharmacodynamics - Change From Baseline in Waist Circumference at Days 15, 29, 57, 85, and 113
Description	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.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 15	-1.056 (2.953)	-0.998 (2.961)
Day 29	-0.656 (3.654)	-2.010 (2.625)
Day 57	-0.316 (3.520)	-2.054 (4.106)
Day 85	0.252 (3.379)	-1.346 (3.894)
Day 113	1.625 (2.394)	-0.580 (4.099)

27. Secondary Outcome

Title	Pharmacodynamics - Inflammatory Marker: Change From Baseline in Fibrinogen at Days 29, 57, 85, and 113
Description	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.
Time Frame	Baseline (Day 1), Days 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 29	-1.450 (1.265)	-2.474 (1.418)
Day 57	-0.524 (1.309)	-2.220 (0.756)
Day 85	-1.340 (1.492)	-1.748 (1.000)
Day 113	-0.295 (1.936)	-1.150 (1.841)

28. Secondary Outcome

Title	Pharmacodynamics - Inflammatory Marker: Change From Baseline in Haptoglobin at Days 29, 57, 85, and 113
Description	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.
Time Frame	Baseline (Day 1), Days 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 29	-0.086 (0.102)	-0.350 (0.244)
Day 57	0.068 (0.118)	-0.300 (0.209)
Day 85	0.066 (0.077)	-0.298 (0.236)
Day 113	0.178 (0.208)	-0.058 (0.081)

29. Secondary Outcome

Title	Pharmacodynamics - Inflammatory Marker: Change From Baseline in Interleukin-6 at Days 29, 57, 85, and 113
Description	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.
Time Frame	Baseline (Day 1), Days 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 29	0.036 (0.080)	0.142 (0.751)
Day 57	0.100 (0.224)	-0.092 (1.096)
Day 85	0.142 (0.243)	0.062 (0.809)
Day 113	0.143 (0.285)	0.078 (0.534)

30. Secondary Outcome

Title	Pharmacodynamics - Inflammatory Marker: Change From Baseline in Tumor Necrosis Factor Alpha at Days 29, 57, 85, and 113
Description	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.
Time Frame	Baseline (Day 1), Days 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 29	-0.134 (0.437)	-0.460 (0.857)
Day 57	0.068 (0.388)	-0.270 (0.651)
Day 85	-0.068 (0.416)	-0.622 (0.939)
Day 113	0.163 (0.534)	-0.445 (0.988)

31. Secondary Outcome

Title	Pharmacodynamics - Inflammatory Marker: Change From Baseline in Plasminogen Activator Inhibitor-1 at Days 29, 57, 85, and 113
Description	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.
Time Frame	Baseline (Day 1), Day 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific timepoints.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Day 29	-8.95 (14.19)	-1.40 (10.33)
Day 57	9.68 (32.87)	2.46 (15.03)
Day 85	-2.43 (7.57)	2.62 (23.77)
Day 113	5.75 (26.71)	5.40 (5.42)

32. Secondary Outcome

Title	Pharmacodynamics - Change From Baseline in Pediatric Quality of Life (PedsQL™) (Version 4.0) Generic Core Scales at Day 85
Description	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.
Time Frame	Baseline (Day 1), Day 85

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'number analyzed' signifies participants who were evaluable for this outcome measure at the specific categories.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Parent	-3.80 (13.76)	-13.04 (11.32)
Participants	-3.04 (1.42)	-3.04 (9.01)

33. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
Description	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.
Time Frame	From Screening visit (signature of informed consent) up to last dose of study drug + 30 days (i.e., up to Day 113)

Outcome Measure Data

Analysis Population Description

Analysis was performed safety population that included participants who had received at least one dose of study drug and had at least one post-baseline safety assessment.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Participants with TEAEs	2 40%	0 0%
Participants with Serious TEAEs	0 0%	0 0%

34. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Measurement
Description	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.
Time Frame	Baseline (Day 1), Day 85

Outcome Measure Data

Analysis Population Description

Analysis was performed safety population.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Baseline (Day1): Abnormal, clinically significant	0 0%	0 0%
Day 85: Abnormal, clinically significant	0 0%	0 0%

35. Secondary Outcome

Title	Number of Participants With Abnormal Clinical Chemistry Parameters
Description	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.
Time Frame	At Day 85 (i.e., end of treatment)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Total proteins: >ULN and <3 ULN	1 20%	1 20%
Albumin: >ULN and <3 ULN	1 20%	0 0%
CPK: >ULN and <3 ULN	0 0%	1 20%
AST: >ULN and <3 ULN	3 60%	0 0%
ALT: >ULN and <3 ULN	3 60%	4 80%
ALT: >=3 ULN and <5 ULN	1 20%	0 0%
ALT: >=5 ULN	1 20%	0 0%
GGT: >ULN and <3 ULN	2 40%	2 40%
GGT: >=3 ULN and <5 ULN	1 20%	0 0%
GGT: >=5 ULN	1 20%	0 0%
ALP: >ULN and <3 ULN	1 20%	0 0%
Total Bilirubin: >ULN and <3 ULN	0 0%	1 20%
Conjugated Bilirubin: >ULN and <3 ULN	0 0%	1 20%
C Reactive Protein: >ULN and <3 ULN	0 0%	1 20%
Fasting plasma glucose: >ULN and <3 ULN	1 20%	0 0%
Fasting insulin: >ULN and <3 ULN	3 60%	5 100%
Fasting insulin: >=3 ULN and <5 ULN	2 40%	0 0%
C-peptide: >ULN and <3 ULN	4 80%	2 40%
Hemoglobin A1C: >ULN and <3 ULN	1 20%	0 0%

36. Secondary Outcome

Title	Number of Participants With Abnormal Hematology and Coagulation Parameters
Description	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.
Time Frame	At Day 85 (i.e., end of treatment)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Haemoglobin: >ULN and <3 ULN	0 0%	0 0%
Hematocrit: >ULN and <3 ULN	0 0%	0 0%
RBC: >ULN and <3 ULN	0 0%	1 20%
WBC: >ULN and <3 ULN	0 0%	0 0%
Neutrophils: >ULN and <3 ULN	0 0%	0 0%
Eosinophils: >ULN and <3 ULN	0 0%	0 0%
Basophils: >ULN and <3 ULN	0 0%	0 0%
Lymphocytes: >ULN and <3 ULN	0 0%	0 0%
Monocytes: >ULN and <3 ULN	0 0%	0 0%
Platelets: >ULN and <3 ULN	0 0%	0 0%
PT: >ULN and <3 ULN	0 0%	0 0%
INR: >ULN and <3 ULN	0 0%	0 0%

37. Secondary Outcome

Title	Number of Participants With Abnormal Urinalysis Parameters
Description	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.
Time Frame	At Day 85 (i.e., end of treatment)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Alpha-1 Microglobulin: >ULN and <3 ULN	0 0%	0 0%
N-Acetyl Glucosamide: >ULN and <3 ULN	0 0%	0 0%
Neutrophil Gelatinase-associated: >ULN and <3 ULN	0 0%	0 0%
Albumin: : >ULN and <3 ULN	0 0%	0 0%
Creatinine	0 0%	0 0%

38. Secondary Outcome

Title	Number of Participants With Abnormal Vital Signs
Description	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)'.
Time Frame	At Day 85 (i.e., end of treatment)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	5	5
Systolic Blood Pressure:Abnormal, not clinically significant	0 0%	0 0%
Systolic Blood Pressure: Abnormal, clinically significant	0 0%	0 0%
Diastolic Blood Pressure: Abnormal, not clinically significant	0 0%	0 0%
Diastolic Blood Pressure: Abnormal, clinically significant	0 0%	0 0%
Heart Rate: Abnormal, not clinically significant	0 0%	0 0%
Heart Rate: Abnormal, clinically significant	0 0%	0 0%

39. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormalities in Physical Examination at Baseline, Days 15, 29, 57, 85, and 113
Description	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.
Time Frame	Baseline (Day 1), Days 15, 29, 57, 85, and 113

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population. Here, 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Elafibranor 80 mg	Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.	Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
Measure Participants	4	2
Baseline (Day 1)	4 80%	2 40%
Day 15	0 0%	0 0%
Day 29	1 20%	0 0%
Day 57	0 0%	0 0%
Day 85	0 0%	0 0%
Day 113	0 0%	0 0%

Adverse Events

Time Frame	All AEs were collected from screening through 30 days after last dose of study drug (i.e., up to Day 113) regardless of seriousness or relationship to study drug.
Adverse Event Reporting Description	Reported AEs were TEAEs that started prior to first study drug dose and that worsened after, and the AEs that started on or after first study drug dose. Analysis was performed on safety population.
Arm/Group Title	Elafibranor 80 mg		Elafibranor 120 mg
Arm/Group Description	Participants received Elafibranor 80 mg tablets orally once daily for 12 weeks.		Participants received Elafibranor 120 mg tablets orally once daily for 12 weeks.
All Cause Mortality
	Elafibranor 80 mg		Elafibranor 120 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Serious Adverse Events
	Elafibranor 80 mg		Elafibranor 120 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Elafibranor 80 mg		Elafibranor 120 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		0/5 (0%)
Hepatobiliary disorders
Hepatomegaly	1/5 (20%)	1	0/5 (0%)	0
Infections and infestations
Gastroenteritis viral	1/5 (20%)	1	0/5 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	1/5 (20%)	1	0/5 (0%)	0

Limitations/Caveats

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. Therefore, participants >=12 to <=17 years of age were only involved in this study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor retains exclusive ownership of all data, results, reports, findings, discoveries, and any other information collected during this study; these may not be published, given, or disclosed, either in part or in whole, by the Investigator or by any person under his/her authority to any third party without the prior express consent of the Sponsor.