Proof of Concept Study on Pitolisant Effect on Autism Spectrum Disorders in Children and Adolescents

Study Overview
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Brief Summary
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Proof of concept, multicenter, randomized, double-blind, placebo-controlled, parallel-group, study to investigate the effect, safety, tolerability and pharmacokinetics of pitolisant in male children and adolescents with Autism Spectrum Disorders.

Detailed Description
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First clinical study to assess the effect of BF2.649 in male children and adolescent with a diagnosis of Autism spectrum disorders according to DSM-5 criteria and confirmed by the Autism Diagnostic Observation Schedule (ADOS-2) or Autism Diagnostic Interview-Revised (ADI-R) over a 12-weeks period.

Official Title
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An Exploratory, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Effect and Safety of Pitolisant in Children and Adolescents With Autism Spectrum Disorders

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Pitolisant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants and their parent(s)/legal guardian(s) are willing and able to give informed assent and consent for participation in the study. Male children and adolescents aged from 6 to 17 inclusive for the duration of study participation. Diagnosis of autism spectrum disorders (ASD) as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria confirmed by the Autism Diagnostic Observation Schedule (ADOS-2) or the Autism Diagnostic Interview-Revised (ADI-R). Intelligence Quotient (IQ) ≥ 70 using Wechsler Intelligence Scale. Social Responsiveness Scale Second Edition (SRS-2) total T-score ≥ 66 at screening and baseline. Exclusion Criteria: Previous genetic diagnosis of ASD-known syndromic ASD (e.g., Fragile X syndrome, Angelman syndrome, Prader-Willi, Rett's syndrome, tuberous sclerosis, Dup15q syndrome). History of suicidal behavior or suicidal ideation in the past 12 months, or a positive answer to questions 4 or 5 on the Columbia-Suicide-Severity Rating Scale (C-SSRS) at screening and/or baseline, and/or is a significant risk for suicidal behavior per investigator judgement. History or current diagnosis of epilepsy or any seizure occurring after the age of 5. Clinically significant deviation from normal on 12-lead ECG that results in an active medical problem, per investigator judgement or, with a corrected QT interval by Fridericia (QTcF) > 450ms at screening. Severe hepatic impairment (Child Pugh C) or with any other hepatic significant abnormality in the physical examination or alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) ≥ 2x Upper Limit of Normal (ULN) for age at laboratory results.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pitolisant<br>One tablet of pitolisant 5 mg, two tablets of pitolisant 5 mg, one tablet of pitolisant 20 mg or two tablets of pitolisant 20 mg per day for 12 weeks. | Drug: Pitolisant<br>* histamine H3 receptor antagonist/inverse agonist<br>* Other names: BF2.649;|
| Placebo Comparator: Placebo<br>One or two tablets of matching placebo per day for 12 weeks. | Drug: Placebo<br>* Matching placebo of pitolisant tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Social Responsiveness Scale Second Edition (SRS-2) total score | 65-item informant-based rating scale designed specifically for use in Autism Spectrum Disorders to quantitatively measure an individual's ability to engage in emotionally appropriate reciprocal social behavior with higher scores indicating greater impairment. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vineland Adaptive Behavior Scale III (VABS III) total score | Instrument that measures socialization, communication, daily living skills, motor skills and maladaptive behavior of individuals with intellectual disabilities | 12 weeks | 
| Incidence of Treatment-Emergent adverse events (AEs) as assessed by AEs collection | Safety assessment of pitolisant based on adverse events (AEs) reporting during the treatment pe | 12 weeks |