Pimavanserin for the Treatment of Irritability Associated With Autism Spectrum Disorder

Irritability Associated With Autism Spectrum Disorder Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05523895
• Other study ID #: ACP-103-069
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: August 9, 2022
• Est. completion date: September 2024

Study information

• Verified date: June 2024
• Source: ACADIA Pharmaceuticals Inc.
• Contact: Sharon Ortiz
• Phone: 646-397-7336
• Email: Sharon.Ortiz[@]acadia-pharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 228
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive
• Irritability Associated With Autism Spectrum Disorder

Intervention

Drug:
• Pimavanserin
Pimavanserin
• Placebo
Pimavanserin matching placebo

Locations

Country	Name	City	State
Australia	Monash Health	Clayton	Victoria
Australia	Murdoch Children's Research Institute	Parkville	Victoria
Australia	Children's Health Queensland Hospital and Health Service	South Brisbane	QDL
France	Centre Hospitalier Charles Perrens	Bordeaux
France	Centre de Ressources Autisme Rhône-Alpes - Center Hospitalier le Vinatier	Bron
France	CHU de Nantes	Nantes
France	L'Assistance Publique - Hôpitaux de Paris, labélisé Institut Carnot	Paris
France	Centre Hospitalier Universitaire (C.H.U) de Rouen	Rouen
Hungary	Magyarországi Református Egyház Bethesda Gyermekkórháza	Budapest
Hungary	Vadaskert Hospital	Budapest
Hungary	Békés Megyei Központi Kórház	Gyula
Hungary	Szegedi Tudományegyetem	Szeged
Italy	Azienda Ospedaliero Universitaria (AOU) Consorziale Policlinico	Bari
Italy	La Nostra Famiglia - Scientifica IRCCS Eugenio Medea	Bosisio Parini
Italy	The Childhood and Adolescence Neuropsychiatry Clinic - University of Cagliari and Pediatric Hospital "A. Cao" - ASL 8 of Cagliari	Cagliari
Italy	Policlinico Riuniti - Azienda Ospedaliero Universitaria	Foggia
Italy	IRCCS Istituto Giannina Gaslini	Genova
Italy	Azienda Ospedaliera Universitaria "Federico II"	Napoli
Italy	Fondazione Istituto Neurologico Nazionale Casimiro Mondino - IRCCS	Pavia
Italy	Fondazione PTV - Policlinico Tor Vergata	Roma
Italy	IRCCS Ospedale Pediatrico Bambino Gesù	Rome
Italy	Azienda Ospedaliera-Universitaria Senese	Siena
Italy	Azienda Ospedaliera Universitaria Integrata di Verona (AOUI)	Verona
Poland	Centrum Badan Klinicznych PI-House Sp. z o.o.	Gdansk
Poland	Gdanskie Centrum Zdrowia Sp. z o.o.	Gdansk
Poland	NAVICULA - Centrum Diagnozy i Terapii Autyzmu	Lódz
Poland	Centrum Neuropsychiatrii NEUROMED SP ZOZ	Wroclaw
Poland	Ginemedica Sp. Zoo, S.K.	Wroclaw
Poland	MedicMental Indywidualna Specjalistyczna Praktyka Lekarska Monika Szewczuk-Boguslawska	Wroclaw
Serbia	Institute of Mental Health	Belgrade
Serbia	University Clinical Center Kragujevac, Clinic for Psychiatry	Kragujevac
Serbia	University Clinical Center Nis, Center for Mental Health	Nis
Serbia	Clinical Center of Vojvodina, Clinic for Psychiatry	Novi Sad
Spain	Hospital General de Alicante	Alicante
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Institut Global d´Atenció Integral del Neurodesenvolupament (IGAIN)	Barcelona
Spain	Complejo Asistencial Universitario de Burgos	Burgos
Spain	Hospital Infantil Universitario Niño Jesús	Madrid
Spain	Hospital Universitario Infanta Leonor	Madrid
Spain	Complejo Asistencial de Zamora	Zamora
United States	Quest Therapeutics of Avon Lake dba Haidar Almhana Nieding LLC	Avon Lake	Ohio
United States	Neurobehavorial Medical Group	Bloomfield Hills	Michigan
United States	1st Allergy and Clinical Research Group, d/b/a IMUNOe Research Centers	Centennial	Colorado
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Relaro Medical Trials, LLC	Dallas	Texas
United States	Cedar Clinical Research	Draper	Utah
United States	Eastside Therapeutic Resource, Inc. dba Core Clinical Research	Everett	Washington
United States	The EHS Medical Practice, PA, D/B/A Sarkis Clinical Trials	Gainesville	Florida
United States	Cortica Inc. (Glendale)	Glendale	California
United States	Red Oak Psychiatry Associates, PA	Houston	Texas
United States	Clinical Research of Southern Nevada, LLC	Las Vegas	Nevada
United States	Axcess Medical Research	Loxahatchee Groves	Florida
United States	AMR Baber Research Incorporated	Naperville	Illinois
United States	Jersey Shore University Medical Center, a division of HMH Hospitals Corporation	Neptune	New Jersey
United States	APG Research, LLC	Orlando	Florida
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Southwest Autism Research & Resource Center	Phoenix	Arizona
United States	AIM Trials, LLC	Plano	Texas
United States	Cortica Inc. (San Rafael)	San Rafael	California
United States	ERG Clinical Research - New York, PLLC DBA Richmond Behavioral Associates	Staten Island	New York
United States	MultiCare Health System	Tacoma	Washington
United States	Children's Research Institute	Washington	District of Columbia
United States	Research Foundation for Mental Hygiene, Inc.	White Plains	New York

Sponsors (1)

Lead Sponsor	Collaborator
ACADIA Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Australia,  France,  Hungary,  Italy,  Poland,  Serbia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline at Week 6 in caregiver-rated Aberrant Behavior Checklist (ABC) Irritability subscale score	The Aberrant Behavior Checklist (ABC) is a caregiver-rated scale comprised of five empirically-derived subscales encompassing 58 items that describe various behavior problems It measures domains of irritability Lethargy/Social Withdrawal, Stereotypic Behavior, Hyperactivity/noncompliance, and Inappropriate Speech. ABC-Irritability is one of the subscales and comprises of 15 items. Minimum score is 0, maximum is 45. The ABC will be administered at Screening and Baseline, and at all post-Baseline visits from Week 1 through Week 6. A score for each item ranges from 0 indicating "not at all a problem" to 3 indicating "the problem is severe in degree". Subscale scores are calculated by summing the items within that subscale. Higher scores indicate greater impairment.	6 weeks
Secondary	Change from Baseline at Week 6 in caregiver-rated ABC subscale scores: Stereotypic Behavior; Lethargy; Hyperactivity; Inappropriate speech		6 weeks
Secondary	Change from Baseline at Week 6 in Clinical Global Impression-Severity (CGI-S) of Irritability score		6 weeks
Secondary	Clinical Global Impression-Improvement (CGI-I) of irritability score at Week 6		6 weeks
Secondary	Change from Baseline at Week 6 in Repetitive Behavior Scale-Revised (RBS-R) scores		6 weeks
Secondary	Change from Baseline at Week 6 in Vineland Adaptive Behavior Scales (VABS)-Socialization subscale score		6 weeks
Secondary	Change from Baseline at Week 6 in Caregiver Strain Questionnaire (CGSQ) scores		6 weeks
Secondary	Proportion of patients with at least 25% reduction from Baseline in ABC-Irritability subscale score at Week 6		6 weeks
Secondary	Proportion of patients with CGI-I of irritability score of 1 (very much improved) or 2 (much improved) at Week 6		6 weeks
Secondary	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		6 weeks