Elafibranor, PK and Safety in Children and Adolescents 8 to 17 Years of Age With Non Alcoholic Steatohepatitis (NASH)
Condition: Non Alcoholic Steatohepatitis
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease
Intervention: Elafibranor 80mg; Elafibranor 120mg
Intervention description: Once daily oral intake of elafibranor 80 mg during 3 months; Once daily oral intake of elafibranor 120 mg during 3 months
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 8 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Pediatric; Pharmacokinetics

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).
    

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.

        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