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

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ClinicalTrials.gov Identifier: NCT03883607
Recruitment Status : Not yet recruiting
First Posted : March 21, 2019
Last Update Posted : April 16, 2019
Sponsor:
Information provided by (Responsible Party):
Genfit

Brief Summary:
The study is being conducted in order to assess the pharmacokinetics and the safety of elafibranor following once daily administration of two dose levels of elafibranor (80 mg and 120mg) during 3 months in children and adolescent population (8 to 17 years of age) with NASH.

Condition or disease Intervention/treatment Phase
Non Alcoholic Steatohepatitis Drug: Elafibranor 80mg Drug: Elafibranor 120mg Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 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)
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020


Arm Intervention/treatment
Experimental: 80mg
elafibranor 80mg
Drug: Elafibranor 80mg
Once daily oral intake of elafibranor 80 mg during 3 months
Other Name: GFT505

Experimental: 120mg
elafibranor 120mg
Drug: Elafibranor 120mg
Once daily oral intake of elafibranor 120 mg during 3 months
Other Name: GFT505




Primary Outcome Measures :
  1. Plasma concentrations of elafibranor and its active metabolite GFT1007 [ Time Frame: Day 1 at pre-dose; Day 29 and 30 at pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post dose ; Day 85 24 hours after last dose ]
    Pharmacokinetic analysis


Secondary Outcome Measures :
  1. Change from baseline in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) and other liver markers [ Time Frame: From day 1 to day 85 ]
  2. Change from baseline in glucose homeostasis makers (Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] and fasting insulin), as a continuous measure [ Time Frame: From day 1 to day 85 ]
  3. Change from baseline in serum total cholesterol [ Time Frame: From day 1 to day 85 ]
  4. Change from baseline in serum non high-density lipoprotein cholesterol [ Time Frame: From day 1 to day 85 ]
  5. Change from baseline in serum low-density lipoprotein cholesterol [ Time Frame: From day 1 to day 85 ]
  6. Change from baseline in serum triglycerides [ Time Frame: From day 1 to day 85 ]
  7. Change from baseline in serum calculated very low-density lipoprotein [ Time Frame: From day 1 to day 85 ]
  8. Change from baseline in serum apolipoprotein A-I [ Time Frame: From day 1 to day 85 ]
  9. Change from baseline in serum apolipoprotein B [ Time Frame: From day 1 to day 85 ]
  10. Change from baseline in body weight [ Time Frame: From day 1 to day 85 ]
  11. Change from baseline in BMI z-score [ Time Frame: From day 1 to day 85 ]
  12. Change from baseline in waist circumference [ Time Frame: From day 1 to day 85 ]
  13. Change from baseline in Fibrinogen [ Time Frame: From day 1 to day 85 ]
  14. Change from baseline in Haptoglobin [ Time Frame: From day 1 to day 85 ]
  15. Change from baseline in Tumor Necrosis Factor alpha [ Time Frame: From day 1 to day 85 ]
  16. Change from baseline in Interleukin-6 [ Time Frame: From day 1 to day 85 ]
  17. Change from baseline in Plasminogen Activator Inhibitor [ Time Frame: From day 1 to day 85 ]
  18. Change from baseline in Pediatric Quality of Life (PedsQL™) 4.0 Generic Core Scales [ Time Frame: From day 1 to day 85 ]

    This scale is a modular approach to measure health-related quality of life (HRQOL) in healthy children and adolescents and those with acute and chronic health conditions. CHILD and PARENT Reports for Children (ages 8-12), Teens (ages 13-18) are used in the study. The PedsQL model integrates generic core scales (Physical 8 items, Emotional 5 items, Social 5 items and School functioning 5 items) into one measurement system (23 items).

    Item scaling: 5-point Likert scale from 0 (Never) to 4 (Almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows 0=100, 1=75, 2=50, 3=25, 4=0.

    Psychosocial Health Summary Score is the sum of the items over the number of items answered in the Emotional, Social, and School Functioning Scales. Physical Health Summary Score is the same as the Physical Functioning Scale Score. Total Scale Score is the sum of all the items over the number of items answered on all the Scales.

    Higher scores indicate better HRQOL.


  19. Number of participants with treatment emergent adverse events (TEAE) [ Time Frame: From day 1 to day 85 ]
    TEAEs will be summarized displaying the number of TEAEs along with the number and percentage of participants with at least one TEAE according to: Number of AEs, Severity and relation to study drug.

  20. Number of subjects With Clinically Significant Abnormalities in 12-lead Electrocardiogram [ Time Frame: From day 1 to day 85 ]
    The number of subjects with normal and abnormal ECG findings will be summarized for each treatment group at each time point. Clinical significance will be determined by the investigator.

  21. Number of subjects with abnormal clinical chemistry parameters [ Time Frame: From day 1 to day 85 ]
    Blood samples will be collected for the assessment of following clinical chemistry parameters: creatinine, creatinine clearance (eGFR), total protein, albumin, electrolytes (sodium, potassium, chloride, calcium), uric acid, urea, Creatinine Phosphokinase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferases, alkaline phosphatase, total and conjugated bilirubin, High-sensitivity C-reactive Protein, fasting plasma glucose, fasting insulin, HOMA-IR, fructosamine, C-peptide, free fatty acids, Glycated haemoglobin, thyroid stimulating hormon.

  22. Number of subjects with abnormal hematology and coagulation parameters. [ Time Frame: From day 1 to day 85 ]
    Blood samples will be collected for the assessment of following hematology parameters: Hemoglobin, hematocrit, red blood cells RBC), white blood cells (WBC) platelet count, differential count, reticulocyte count and prothrombin (PT) and international normalized ratio (INR).

  23. Number of subjects with abnormal Urinalysis parameters [ Time Frame: From day 1 to day 85 ]
    Samples will be collected to measure: specific gravity, pH, protein, glucose, ketones, bilirubin, urobilinogen, blood, nitrite, leukocytes, α1 microglobulin, N-acetyl-beta-glucosaminidase (β-NAG), Neutrophil gelatinase-associated lipocalin (N-Gal), albumin and creatinine.

  24. Number of subjects with abnormal vital signs. [ Time Frame: From day 1 to day 85 ]
    Vital signs, including systolic and diastolic blood pressure (mm Hg) and heart rate (bpm) will be measured after the subject has been in a sitting position for 5 minutes.

  25. Number of subjects with abnormal physical examination [ Time Frame: From day 1 to day 85 ]
    The physical examination will include an examination of general appearance, skin, eyes, ears, nose, throat, neck/thyroid, lungs, heart, upper/lower extremities, lymph nodes, abdomen, musculoskeletal system and basic neurological assessment. Additional systems will be evaluated as needed.

  26. Change from baseline in serum high-density lipoprotein cholesterol [ Time Frame: From day 1 to day 85 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   8 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Are 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 non-alcoholic steatohepatitis (NASH) confirmed by histological evaluation (with or without fibrosis) from a liver biopsy obtained within 24 months prior to Randomization;
  • Has an alanine aminotransferase (ALT) level greater than 50 IU/L, at Screening;
  • Has a Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) greater than or equal to 5, at Screening;
  • Has a Body Mass Index z-score (BMI z-score) (also referred to as BMI-for-age percentile) greater than or equal to 85th percentile for age and gender at Screening;
  • Has a Hemoglobin A1C (HbA1c) less than or equal to 8.5%. If the patient has Type 2 diabetes and is taking anti-diabetic therapy (e.g., metformin or insulin), treatment must have been started at least 3 months prior to Screening and the dose must be stable for at least 3 months prior to Screening and should remain stable through Randomization;
  • Sexually active female participants of childbearing potential must 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:

  • Has history of bariatric surgery or planned surgery during the study period;
  • Has known history of heart disease;
  • Has 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;
  • Has a known history of Type 1 diabetes;
  • Has a known history of acquired immunodeficiency syndrome or positive screening for human immunodeficiency virus antibodies at Screening Visit;
  • Has a documented weight loss of more than 5% during the 6-month period prior to Randomization;
  • Has 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.
  • Has 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;
  • Has AST and/or ALT greater than 8 fold the upper limit of normal;
  • Is pregnant, lactating or is planning to become pregnant during the study;

Other exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03883607


Contacts
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Contact: Genfit +33(0)320164000 clinicaltrial@genfit.com

Sponsors and Collaborators
Genfit
Investigators
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Study Director: Pascal Birman, MD Genfit

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Responsible Party: Genfit
ClinicalTrials.gov Identifier: NCT03883607     History of Changes
Other Study ID Numbers: GFT505E-218-1
First Posted: March 21, 2019    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases