Clinical Trial Results:
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)
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Summary
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EudraCT number |
2019-003400-12 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
16 Jun 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Oct 2021
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First version publication date |
13 Oct 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GFT505E-218-1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03883607 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GENFIT
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Sponsor organisation address |
Parc Eurasanté, 885, avenue Eugène Avinée, LOOS, France, 59120
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Public contact |
Clinical Trials Contact Point, GENFIT, +01 6179536469, clinicaltrial@genfit.com
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Scientific contact |
Carol Addy, MD MMSc, Study Director, GENFIT, +01 6179536469, clinicaltrial@genfit.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001857-PIP01-15 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Jun 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Jun 2020
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The main objective of the study was to assess the pharmacokinetics (PK) of elafibranor and its active metabolite GFT1007, following once daily oral administration of two dose levels of elafibranor (80 milligrams [mg] and 120 mg) to children and adolescents, 8 to 17 years of age (inclusive).
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Protection of trial subjects |
This study was conducted in accordance with the principles laid down by the 18th World Medical Assembly (Helsinki, 1964) and all applicable amendments laid down by the World Medical Assemblies, and the Good Clinical Practice (GCP) guideline (CHMP, 2016). This study also complied with applicable local regulatory requirements and laws of each country in which the study was performed, as well as any applicable guidelines.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Jun 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
10
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 2 centers in the United States from 25 June 2019 and 16 June 2020. A total of 27 subjects were screened, of which 10 subjects were enrolled and randomised (1:1 ratio) to receive elafibranor 80 mg/120 mg sequentially. A total of 17 subjects failed screening mainly due to not meeting eligibility criteria. | |||||||||
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Pre-assignment
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Screening details |
Screening was performed up to 4 weeks before study drug administered. Randomisation: stratified by age (Cohort 1: >=12 to <=17 years; Cohort 2: >=8 to <=11 years) and historical fibrosis severity stage (stratum 1:0 to 1; stratum 2:2 to 3). Due to lack of efficacy, study was prematurely terminated, only Cohort 1 subjects were involved in this study. | |||||||||
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Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Elafibranor 80 mg | |||||||||
Arm description |
Subjects received elafibranor 80 mg tablets orally once daily for 12 weeks. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Elafibranor 80mg
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Investigational medicinal product code |
GFT505
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Elafibranor tablet orally once daily for 12 weeks.
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Arm title
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Elafibranor 120mg | |||||||||
Arm description |
Subjects received elafibranor 120 mg tablets orally once daily for 12 weeks. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Elafibranor 120mg
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Investigational medicinal product code |
GFT505
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Elafibranor tablet orally once daily for 12 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Elafibranor 80 mg
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Reporting group description |
Subjects received elafibranor 80 mg tablets orally once daily for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Elafibranor 120mg
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Reporting group description |
Subjects received elafibranor 120 mg tablets orally once daily for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Elafibranor 80 mg
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Reporting group description |
Subjects received elafibranor 80 mg tablets orally once daily for 12 weeks. | ||
Reporting group title |
Elafibranor 120mg
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Reporting group description |
Subjects received elafibranor 120 mg tablets orally once daily for 12 weeks. | ||
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End point title |
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Elafibranor and its Active Metabolite (GFT1007) [1] | ||||||||||||||||||
End point description |
Cmax was defined as maximum observed plasma concentration. Analysis was performed on PK population that included all subjects 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.
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End point type |
Primary
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End point timeframe |
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
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were performed; no inferential statistical analyses were performed. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of Elafibranor and Active Metabolite (GFT1007) [2] | ||||||||||||||||||
End point description |
Tmax was defined as time to reach maximum observed plasma concentration. Analysis was performed on PK population.
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End point type |
Primary
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End point timeframe |
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
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were performed; no inferential statistical analyses were performed. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Pharmacokinetics: Area Under The Plasma Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Elafibranor and Active Metabolite (GFT1007) [3] | ||||||||||||||||||
End point description |
AUC0-24 was defined as the area under the plasma concentration versus time curve of the study drug from time 0 to 24 hours. Analysis was performed on PK population.
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End point type |
Primary
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End point timeframe |
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
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were performed; no inferential statistical analyses were performed. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Pharmacokinetics: Terminal Elimination Half-life ( t½) of Elafibranor and Active Metabolite (GFT1007) [4] | ||||||||||||||||||
End point description |
Plasma t1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration. Analysis was performed on PK population. Here, "n= number analysed" signifies those subjects who were evaluable for specified category. Here, '99999' indicates that standard deviation was not estimated as only single subject was analysed for the each specified category.
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End point type |
Primary
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End point timeframe |
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
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were performed; no inferential statistical analyses were performed. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Pharmacokinetics: Plasma Trough Concentrations (Ctrough) of Elafibranor and Active Metabolite (GFT1007) [5] | ||||||||||||||||||
End point description |
Ctrough was defined as the plasma concentration of study drug observed just before treatment administration during repeated dosing. Analysis was performed on PK population.
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End point type |
Primary
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End point timeframe |
Pre-dose on Day 1 and 29
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistics were performed; no inferential statistical analyses were performed. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point 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. Analysis was performed on intent-to-treat (ITT) population that had included subjects who were randomised and had received at least 1 dose of the study drug. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Pharmacodynamics - Other Liver Markers: Change From Baseline in Adiponectin at Days 29, 57, 85 and 113 | ||||||||||||||||||||||||
End point 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 29, 57, 85 and 113
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point 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 | ||||||||||||||||||||||||||||||||||||
End point 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 29, 57, 85 and 113
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
Pharmacodynamics - Other Liver Markers: Change From Baseline in Ferritin at Days 29, 57, 85 and 113 | ||||||||||||||||||||||||
End point 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 29, 57, 85 and 113
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point 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 | ||||||||||||||||||||||||||||||||||||
End point 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 29, 57, 85 and 113
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point 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 | ||||||||||||||||||||||||||||||||||||||||||||||||
End point 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 29, 57, 85 and 113
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Pharmacodynamics - Other Liver Markers: Change From Baseline in Alpha-2 Macroglobulin at Days 29, 57, 85 and 113 | ||||||||||||||||||||||||
End point 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 29, 57, 85 and 113
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Pharmacodynamics - Glucose Homeostasis Markers: Change From Baseline in Fasting Plasma Glucose (FPG) at Days 15, 29, 57, 85 and 113 | |||||||||||||||||||||||||||
End point 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point 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 | |||||||||||||||||||||||||||
End point 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. Baseline was defined as the last measurement before first intake of study treatment on Day 1. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Pharmacodynamics - Glucose Homeostasis Markers: Change From Baseline in Fasting Insulin at Days 15, 29, 57, 85 and 113 | |||||||||||||||||||||||||||
End point 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Total Cholesterol (TC) at Days 15, 29, 57, 85 and 113 | |||||||||||||||||||||||||||
End point description |
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point 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 | |||||||||||||||||||||||||||
End point description |
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||
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End point title |
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum High-density Lipoprotein Cholesterol (HDL-C) at Days 15, 29, 57, 85 and 113 | |||||||||||||||||||||||||||
End point description |
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
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End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point title |
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Low-density Lipoprotein (LDL-C) at Days 15, 29, 57, 85 and 113 | |||||||||||||||||||||||||||
End point description |
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point title |
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Triglycerides at Days 15, 29, 57, 85 and 113 | |||||||||||||||||||||||||||
End point description |
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point 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 | |||||||||||||||||||||||||||
End point description |
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point title |
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Apolipoprotein A-1 at Days 15, 29, 57, 85 and 113 | |||||||||||||||||||||||||||
End point description |
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point title |
Pharmacodynamics - Serum Lipid Parameters: Change From Baseline in Serum Apolipoprotein B at Days 15, 29, 57, 85 and 113 | |||||||||||||||||||||||||||
End point description |
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point title |
Pharmacodynamics - Change From Baseline in Body Weight at Days 15, 29, 57, 85 and 113 | |||||||||||||||||||||||||||
End point description |
Baseline was defined as the last measurement before first intake of study treatment on Day 1. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point title |
Pharmacodynamics - Change From Baseline in Body Mass Index (BMI) Z-Score at Days 15, 29, 57, 85 and 113 | |||||||||||||||||||||||||||
End point description |
The BMI for a given age (in years) and gender (male) was converted to an exact z-score. Given a subject’s age, sex, BMI, and an appropriate reference standard, a BMI Z-score (also referred to as BMI-for-age percentile) 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for specified time point.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point title |
Pharmacodynamics - Change From Baseline in Waist Circumference at Days 15, 29, 57, 85 and 113 | |||||||||||||||||||||||||||
End point 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for specified time point.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Fibrinogen at Days 29, 57, 85 and 113 | ||||||||||||||||||||||||
End point 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for specified time point.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 29, 57, 85 and 113
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Haptoglobin at Days 29, 57, 85 and 113 | ||||||||||||||||||||||||
End point 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for specified time point.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 29, 57, 85 and 113
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Interleukin-6 at Days 29, 57, 85 and 113 | ||||||||||||||||||||||||
End point 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for specified time point.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 29, 57, 85 and 113
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Tumor Necrosis Factor Alpha at Days 29, 57, 85 and 113 | ||||||||||||||||||||||||
End point 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for specified time point.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 29, 57, 85 and 113
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Pharmacodynamics - Inflammatory Marker: Change From Baseline in Plasminogen Activator Inhibitor-1 at Days 29, 57, 85, and 113 | ||||||||||||||||||||||||
End point 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for each specified time point. Here, IU/mL was abbreviated as "International units per milliliter".
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 29, 57, 85, and 113
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||||||||||
End point title |
Pharmacodynamics - Change From Baseline in Pediatric Quality of Life (PedsQL™) Generic Core Scales at Day 85 | ||||||||||||||||||
End point description |
The child, adolescent and parent/legal guardian PedsQL™ (version 4.0) generic core scales was used to measure HRQOL. The response information was completed by the subject and by a parent/legal guardian individually. PedsQL 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. Analysis was performed on ITT population. Here, "n= number analysed" signifies those subjects who were evaluable for specified category.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline (Day 1), Day 85
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
||||||||||||||||
End point title |
Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | |||||||||||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical (investigational) product and which does not necessarily to had 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 in-patient hospitalisation/prolongation of existing hospitalisation, 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. Analysis was performed safety population that included subjects who had received at least one dose of study drug and had at least one post-baseline safety assessment.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
From Screening visit (signature of informed consent) up to last dose of study drug + 30 days (i.e., up to Day 113)
|
|||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
||||||||||||||||
End point title |
Number of Subjects With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Measurement | |||||||||||||||
End point description |
ECG measurements were taken with the subjects in resting position for at least 10 minutes. The investigator determined whether abnormal assessment results were clinically significant or not. The number of subjects with abnormal ECG findings were reported. Baseline was defined as the last measurement before first intake of study treatment on Day 1. Analysis was performed safety population.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Baseline (Day 1), Day 85
|
|||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects With Abnormal Clinical Chemistry Parameters | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point 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 that parameter for which at least one value of abnormality were reported and presented in this endpoint. Analysis was performed on safety population.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 85 (i.e., end of treatment)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
End point title |
Number of Subjects With Abnormal Hematology and Coagulation Parameters | |||||||||||||||||||||||||||||||||||||||||||||
End point 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. Analysis was performed on safety population.
|
|||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
At Day 85 (i.e., end of treatment)
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||
End point title |
Number of Subjects With Abnormal Urinalysis Parameters | ||||||||||||||||||||||||
End point description |
Blood samples were collected to assess the following urinalysis parameters: alpha-1 macroglobulin, N-acetyl glucosamide, neutrophil gelatinase-associated lipocalin (NGL), 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. Analysis was performed on safety population.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
At Day 85 (i.e., end of treatment)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point title |
Number of Subjects With Abnormal Vital Signs | |||||||||||||||||||||||||||
End point description |
Vital signs were taken before any invasive procedures. Following vital signs were assessed: systolic blood pressure, diastolic blood pressure, and heart rate. Abnormal vita signs was defined as any abnormal findings in the vital sign parameters and were categorised as ‘abnormal, not clinically significant (NCS)’ and ‘abnormal, clinically significant (CS)’. Analysis was performed on safety population.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
At Day 85 (i.e., end of treatment)
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
End point title |
Number of Subjects With Clinically Significant Abnormalities in Physical Examination at Baseline, Days 15, 29, 57, 85 and 113 | |||||||||||||||||||||||||||
End point 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. Subjects with at least one clinically significant abnormality in physical examination were reported and presented in this endpoint. Baseline was defined as the last measurement before first intake of study treatment on Day 1. Analysis was performed on safety population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline (Day 1), Days 15, 29, 57, 85 and 113
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
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 additional 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.
|
|||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
|
|||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Elafibranor 80 mg
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received elafibranor 80 mg tablets orally once daily for 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Elafibranor 120 mg
|
|||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects received elafibranor 120 mg tablets orally once daily for 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
20 Apr 2020 |
Protocol Amendment 3: The following changes were made to implement safeguards due to COVID-19 restrictions.
- The screening window (i.e., the time from the signing of consent or the screening visit to randomisation) could had been extended up to 8 weeks if no on-site visit was possible earlier. .
- Off-site study procedures could be performed in case a subject could not attend an on-site visit, including safety assessments via phone call, local laboratory assessments, delivery of the study drug to subjects, and visits to the subjects’ homes.
- The randomization visit (Visit 1) was excluded from the off-site options and needed to be completed on-site.
- Safety and drug compliance procedures were updated to include the option of a phone call or, if safe and possible at the time, a direct visit to the subject. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Due to lack of efficacy (but not due to safety) in Phase 3 trial of elafibranor in adult subjects with NASH and fibrosis, this study in pediatric NASH was prematurely terminated and therefore subjects >=12 to <=17 years of age were only involved. | |||
