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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: Pitolisant; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Centre Hospitalier Charles Perrens
  • Nantes, France, 44093
    • Nantes University Hospital
  • Sotteville-lès-Rouen, France, 76300
    • CH Le Rouvray
• Italy
  • Bologna, Italy, 40139
    • IRCCS-Istituto delle Scienze Neurologiche di Bologna
  • Bosisio Parini, Italy, 23842
    • Istituto Scientifico IRCCS E. Medea
  • Cagliari, Italy, 09121
    • Clinica Di Neuropsichiatria Infantile
  • Calambrone, Italy, 56128
    • IRCCS Fondazione Stella Maris
  • Foggia, Italy, 71122
    • A.O.U Ospedali Riuniti di Foggia- Cardiologia (U.O.C)
  • Messina, Italy, 98124
    • IRCCS Centro Neurolesi Bonino Pulejo
  • Napoli, Italy, 80131
    • Università degli Studi di Napoli Federico II
  • Pavia, Italy, 27100
    • IRCCS Instituto Neurologico Casimiro Mondino
  • Siena, Italy, 53100
    • Azienda Ospedaliero-Universitaria Senese
• Spain
  • Barcelona, Spain, 08030
    • Hospital Universitari Vall d'Hebron
  • Burgos, Spain, 09006
    • Hospital Universitario de Burgos
• United Kingdom
  • London, United Kingdom, W1G 9JF
    • Cognition Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pitolisant; 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; histamine H3 receptor antagonist/inverse agonist; Other Names: BF2.649
Placebo Comparator: Placebo; One or two tablets of matching placebo per day for 12 weeks.	Drug: Placebo; Matching placebo of pitolisant tablets

What is the study measuring?

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
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
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

Collaborators and Investigators

• Sponsor: Bioprojet
• Investigators: Principal Investigator: Olivier Bonnot, MD, Prof., Etablissement Public de Santé Barthélemy Durand, Sainte-Geneviève-des-Bois, France

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: July 12, 2023
• First Submitted That Met QC Criteria: July 12, 2023
• First Posted (Actual): July 20, 2023

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; pitolisant
• Other Study ID Numbers: P21-01 / BF2.649

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No