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

NCT03883607 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: GFT505E-218-12019-003400-12
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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).

Conditions

Non Alcoholic Steatohepatitis

Keywords

Pediatric; Pharmacokinetics

Outcome Measures

Primary Outcomes (5)

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

  Cmax was defined as maximum observed plasma concentration.

  Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration

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

  Tmax was defined as time to reach maximum observed plasma concentration.

  Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration

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

  AUC0-24 defined as the area under the plasma concentration versus time curve of the study drug from time 0 to 24 hours.

  Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration

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

  Plasma t1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.

  Day 1: at pre-dose; Day 29: at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8 hours post dose; Day 30 and 85: at 24 hours after previous day dose administration

• Pharmacokinetics: Plasma Trough Concentrations (Ctrough) of Elafibranor and Active Metabolite (GFT1007)

  Ctrough was defined as the plasma concentration of study drug observed just before treatment administration during repeated dosing.

  Pre-dose on Day 1 and 29

Secondary Outcomes (34)

• Pharmacodynamics (PD) - Liver Markers: Change From Baseline in Serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase (GGT), and Alkaline Phosphatase (ALP) at Days 15, 29, 57, 85, and 113

  Baseline (Day 1), Days 15, 29, 57, 85, and 113

• Pharmacodynamics - Other Liver Markers: Change From Baseline in Adiponectin at Days 29, 57, 85, and 113

  Baseline (Day 1), Days 29, 57, 85, and 113

• Pharmacodynamics - Other Liver Markers: Change From Baseline in Cytokeratin 18 (CK-18)/M65 and CK-18/M30 at Days 29, 57, 85, and 113

  Baseline (Day 1), Days 29, 57, 85, and 113

• Pharmacodynamics - Other Liver Markers: Change From Baseline in Ferritin at Days 29, 57, 85, and 113

  Baseline (Day 1), Days 29, 57, 85, and 113

• Pharmacodynamics - Other Liver Markers: Change From Baseline in Fibroblast Growth Factor 19 and Fibroblast Growth Factor 21 at Days 29, 57, 85, and 113

  Baseline (Day 1), Days 29, 57, 85, and 113

Study Arms (2)

Elafibranor 80 mg

EXPERIMENTAL

Participants received Elafibranor 80 mg tablet orally once daily for 12 weeks.

Drug: Elafibranor 80mg

Elafibranor 120 mg

EXPERIMENTAL

Participants received Elafibranor 120 mg tablet orally once daily for 12 weeks.

Drug: Elafibranor 120mg

Interventions

Elafibranor 80mg DRUG

Once daily oral intake of elafibranor 80 mg during 3 months

Also known as: GFT505

Elafibranor 80 mg

Elafibranor 120mg DRUG

Once daily oral intake of elafibranor 120 mg during 3 months

Also known as: GFT505

Elafibranor 120 mg

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Abnormal hemoglobin (with the exception of females with a documented history of a low hemoglobin during menstruation);
• White blood cell count less than 3,500 cells/mm\^3 of blood;
• Platelet count less than150,000 cells/mm\^3 of blood;
• Direct bilirubin greater than 0.3 mg/dL;
• Total bilirubin greater than 1.3 mg/dL unless the patient has a diagnosis of Gilbert disease in which case direct bilirubin, reticulocyte count and haemoglobin must be normal;
• Serum albumin less than 3.5 g/dL;

Sponsors & Collaborators

• Genfit: lead

Study Sites (2)

University of California

San Diego, California, 92103, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Related Publications (1)

• Goyal NP, Mencin A, Newton KP, Durelle J, Carrier C, Ugalde-Nicalo P, Noel B, Mouton J, Vargas D, Magrez D, Tadde B, Birman P, Best BM, Addy C, Schwimmer JB. An Open Label, Randomized, Multicenter Study of Elafibranor in Children With Nonalcoholic Steatohepatitis. J Pediatr Gastroenterol Nutr. 2023 Aug 1;77(2):160-165. doi: 10.1097/MPG.0000000000003796. Epub 2023 Apr 21.

  PMID: 37084342 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Limitations and 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.

Results Point of Contact

• Title: Clinical Head
• Organization: Genfit SA

clinicaltrial@genfit.com

+33320164000

Study Officials

• Carol Addy, MD MMSc

  Genfit

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2019
• First Posted: March 21, 2019
• Study Start: June 25, 2019
• Primary Completion: June 16, 2020
• Study Completion: June 16, 2020
• Last Updated: October 28, 2021
• Results First Posted: October 28, 2021

Record last verified: 2021-09

Locations

US (2)