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

NCT ID: NCT03883607

Last Updated: 2021-10-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-25
• Study Completion Date: 2020-06-16

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Elafibranor 80 mg

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

Group Type: EXPERIMENTAL

Elafibranor 80mg

Intervention Type: DRUG

Once daily oral intake of elafibranor 80 mg during 3 months

Elafibranor 120 mg

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

Group Type: EXPERIMENTAL

Elafibranor 120mg

Intervention Type: DRUG

Once daily oral intake of elafibranor 120 mg during 3 months

Interventions

Elafibranor 80mg

Once daily oral intake of elafibranor 80 mg during 3 months

Intervention Type: DRUG

Elafibranor 120mg

Once daily oral intake of elafibranor 120 mg during 3 months

Intervention Type: DRUG

Other Intervention Names

GFT505; GFT505

Eligibility Criteria

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.

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;

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genfit

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carol Addy, MD MMSc

Role: STUDY_DIRECTOR

Genfit

Locations

University of California

San Diego, California, United States

Columbia University

New York, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37084342 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-003400-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GFT505E-218-1

Identifier Type: -

Identifier Source: org_study_id