Clinical trial NCT05523895: Pimavanserin for the Treatment of Irritability Associated with Autism Spectrum Disorder
Official title: A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Pimavanserin for the Treatment of Irritability Associated with Autism Spectrum Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Irritability Associated with Autism Spectrum Disorder
Keywords: Randomized
Placebo-controlled
Lead sponsor: ACADIA Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2022-08-31
Enrollment: 237
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 6-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel group study in children and adolescents (aged 5 to17 years) with autism spectrum disorder (ASD) with irritability, agitation, or self-injurious behaviors to study the efficacy and safety of pimavanserin

Detailed description: This study will be conducted as a 6-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel group study in children and adolescents (5 through 17 years of age) with ASD with irritability, agitation, or self-injurious behaviors.

Eligibility criteria: INCLUSION CRITERIA:

* Male or female and 5 through 17 years of age
* Informed consent prior to the conduct of any study procedures
* Patients (to the best of his/her ability), parent/legally accepted representative, and designated caregiver (if applicable) are able to understand the nature of the study, follow protocol requirements, and be willing to comply with study drug administration requirements
* Able to swallow a test placebo capsule without difficulty
* Meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for a primary diagnosis of ASD (APA 2013) and diagnosis is confirmed by the Autism Diagnostic Interview-Revised (ADI-R)
* Score ≥18 on the Irritability subscale of the Aberrant Behavior Checklist (ABC)
* Score ≥4 (moderate or greater severity) on the Clinical Global Impression-Severity (CGI-S) of irritability score
* No current comorbid psychiatric disorder other than attention-deficit hyperactivity disorder (ADHD) or anxiety disorder
* Drug-naïve to antipsychotic treatment (or \<2 weeks antipsychotic treatment for any reason), or prior lack of tolerability to adequate dose of any duration of antipsychotic confirmed by caregiver and medical records review
* If patient is undergoing concurrent behavioral therapy for autism related symptoms or behaviors, this non-pharmacological treatment regimen has been stable for at least 4 weeks, and will be consistent throughout the study
* For female patients only: unable to become pregnant or agree to use a highly effective non-hormonal method of contraception. Females of childbearing potential must have a negative pregnancy test

EXCLUSION CRITERIA:

* Requires treatment with a medication prohibited by the protocol, including concomitant psychotropic drugs targeting irritability, including those used off-label (clonidine, guanfacine, and propranolol; lithium, valproate), medications that prolong the QT interval, and strong cytochrome P450 (CYP) 3A4 enzyme (CYP3A4) inhibitors and inducers
* Changes in medications or medication doses (for medical and allowed comorbid psychiatric conditions) in the last 4 weeks
* Any known history of angioedema, serotonin or neuroleptic malignant syndromes, dystonic reaction, or tardive dyskinesia, due to an antipsychotic or psychotropic medication
* At a significant risk of suicide, or is a danger to self or others
* At risk of significant violent behavior to the extent that participation would pose an undue risk to other patients, caregivers, or others
* Positive urine drug test
* Met DSM-5 criteria for substance use disorders within the last 6 months
* Confirmed genetic disorder associated with ASD, a cognitive and/ or behavioral disturbance or profound intellectual disability (IQ ≤50)
* History of seizures, unless seizure-free and off epileptic drugs for at least 6 months
* Any condition that, in the opinion of the Investigator, would interfere with the ability to comply with study instructions, or that might confound the interpretation of the study results or put the subject at undue risk
* Current evidence, or history within the last 12 weeks, of a serious and/or unstable psychiatric, neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies
* Weight \<15 kg
* History or presence on at least one ECG of protocol-defined cardiac conduction abnormalities
* Known family or personal history or symptoms of long QT syndrome or history of cardiac arrhythmias or risk factors for torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and presence of congenital prolongation of the QT interval
* Any member of the household has suffered from COVID-19 or had a COVID-19 (PCR or immunoglobulin) positive test in the last 4 weeks
* One or more clinical laboratory test value outside of protocol-defined limits
* Breastfeeding or lactating, or has a positive pregnancy test result (for patients of childbearing potential)
* Sensitivity to pimavanserin or any of the excipients
* Participating in another clinical study of any investigational drug, device, or intervention
* Participated in greater than 2 interventional pharmaceutical clinical research studies in the last 6 months
* Additional inclusion/exclusion criteria apply. Subjects will be evaluated at screening to ensure that all criteria for study participation are met.

Primary outcomes:
measure: Change from Baseline at Week 6 in caregiver-rated Aberrant Behavior Checklist (ABC) Irritability subscale score
timeFrame: 6 weeks
Secondary outcomes:
measure: Change from Baseline at Week 6 in caregiver-rated ABC subscale scores: Stereotypic Behavior; Lethargy; Hyperactivity; Inappropriate speech
timeFrame: 6 weeks
measure: Change from Baseline at Week 6 in Clinical Global Impression-Severity (CGI-S) of Irritability score
timeFrame: 6 weeks
measure: Clinical Global Impression-Improvement (CGI-I) of irritability score at Week 6
timeFrame: 6 weeks
measure: Change from Baseline at Week 6 in Repetitive Behavior Scale-Revised (RBS-R) scores
timeFrame: 6 weeks
measure: Change from Baseline at Week 6 in Vineland Adaptive Behavior Scales (VABS)-Socialization subscale score
timeFrame: 6 weeks
measure: Change from Baseline at Week 6 in Caregiver Strain Questionnaire (CGSQ) scores
timeFrame: 6 weeks
measure: Proportion of patients with at least 25% reduction from Baseline in ABC-Irritability subscale score at Week 6
timeFrame: 6 weeks
measure: Proportion of patients with CGI-I of irritability score of 1 (very much improved) or 2 (much improved) at Week 6
timeFrame: 6 weeks
measure: Proportion of patients with at least 25% reduction from Baseline in ABC-Irritability subscale score and CGI-I of irritability score of 1 or 2 at Week 6
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Southwest Autism Research & Resource Center
state: Arizona
city: Glendale
country: United States
facility: Cortica Inc. (Glendale)
state: California
city: San Rafael
country: United States
facility: Cortica Inc. (San Rafael)
state: California
city: Centennial
country: United States
facility: 1st Allergy and Clinical Research Group, d/b/a IMUNOe Research Centers
state: Colorado
city: Washington, D.C.
country: United States
facility: Children's Research Institute
state: District of Columbia
city: Gainesville
country: United States
facility: The EHS Medical Practice, PA, D/B/A Sarkis Clinical Trials
state: Florida
city: Orlando
country: United States
facility: APG Research, LLC
state: Florida
city: Naperville
country: United States
facility: AMR Baber Research Incorporated
state: Illinois
city: Las Vegas
country: United States
facility: Clinical Research of Southern Nevada, LLC
state: Nevada
city: Staten Island
country: United States
facility: ERG Clinical Research - New York, PLLC DBA Richmond Behavioral Associates
state: New York
city: Avon Lake
country: United States
facility: Quest Therapeutics of Avon Lake dba Haidar Almhana Nieding LLC
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Relaro Medical Trials, LLC
state: Texas
city: Houston
country: United States
facility: Red Oak Psychiatry Associates, PA
state: Texas
city: Plano
country: United States
facility: AIM Trials, LLC
state: Texas
city: Everett
country: United States
facility: Eastside Therapeutic Resource, Inc. dba Core Clinical Research
state: Washington
city: South Brisbane
country: Australia
facility: Children's Health Queensland Hospital and Health Service
state: QDL
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Parkville
country: Australia
facility: Murdoch Children's Research Institute
state: Victoria
city: Bordeaux
country: France
facility: Centre Hospitalier Charles Perrens
city: Bron
country: France
facility: Centre de Ressources Autisme Rhône-Alpes - Center Hospitalier le Vinatier
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: L'Assistance Publique - Hôpitaux de Paris, labélisé Institut Carnot
city: Budapest
country: Hungary
facility: Vadaskert Hospital
city: Budapest
country: Hungary
facility: Magyarországi Református Egyház Bethesda Gyermekkórháza
city: Gyula
country: Hungary
facility: Békés Megyei Központi Kórház
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem
city: Bari
country: Italy
facility: Azienda Ospedaliero Universitaria (AOU) Consorziale Policlinico
city: Bosisio Parini
country: Italy
facility: La Nostra Famiglia - Scientifica IRCCS Eugenio Medea
city: Cagliari
country: Italy
facility: The Childhood and Adolescence Neuropsychiatry Clinic - University of Cagliari and Pediatric Hospital "A. Cao" - ASL 8 of Cagliari
city: Foggia
country: Italy
facility: Policlinico Riuniti - Azienda Ospedaliero Universitaria
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria "Federico II"
city: Pavia
country: Italy
facility: Fondazione Istituto Neurologico Nazionale Casimiro Mondino - IRCCS
city: Roma
country: Italy
facility: Fondazione PTV - Policlinico Tor Vergata
city: Rome
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesù
city: Siena
country: Italy
facility: Azienda Ospedaliera-Universitaria Senese
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata di Verona (AOUI)
city: Gdansk
country: Poland
facility: Centrum Badań Klinicznych PI-House Sp. z o.o.
city: Gdańsk
country: Poland
facility: Gdańskie Centrum Zdrowia Sp. z o.o.
city: Wrocław
country: Poland
facility: Ginemedica Sp. Zoo, S.K.
city: Wrocław
country: Poland
facility: Centrum Neuropsychiatrii NEUROMED SP ZOZ
city: Wrocław
country: Poland
facility: MedicMental Indywidualna Specjalistyczna Praktyka Lekarska Monika Szewczuk-Boguslawska
city: Łódź
country: Poland
facility: NAVICULA - Centrum Diagnozy i Terapii Autyzmu
city: Belgrade
country: Serbia
facility: Institute of Mental Health
city: Kragujevac
country: Serbia
facility: University Clinical Center Kragujevac, Clinic for Psychiatry
city: Nis
country: Serbia
facility: University Clinical Center Nis, Center for Mental Health
city: Novi Sad
country: Serbia
facility: Clinical Center of Vojvodina, Clinic for Psychiatry
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Barcelona
country: Spain
facility: Institut Global d´Atenció Integral del Neurodesenvolupament (IGAIN)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Burgos
country: Spain
facility: Complejo Asistencial Universitario de Burgos
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Zamora
country: Spain
facility: Complejo Asistencial de Zamora
Study officials:
References: