Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD

Study Overview
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Brief Summary
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Autism spectrum disorder (ASD) consists of deficits in social, communication, and cognitive development, repetitive and stereotypic behaviors. Many ASD patients show notably high levels of irritability, including verbal and physical aggression, self injury, and/or property destruction. Autistic infants tend to avoid eye contact and show little interest in others. This study will assess how safe and effective cariprazine is in treating pediatric participants (5 to 17 years of age) with ASD. Adverse events and change in disease activity will be assessed. Cariprazine is an investigational drug being developed for the treatment of irritability due to ASD. This study is double-blinded means that neither the participants nor the study doctors will know who will be given cariprazine and who will be given placebo (does not contain treatment drug). Study doctors put the participants in 1 of the 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. Approximately 152 participants diagnosed with ASD will be enrolled in approximately 50 sites globally. Participants will receive oral capsules or oral solution of cariprazine or placebo once daily for 8-weeks and will undergo a 12-week safety follow-up period. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, checking for side effects and completing questionnaires.

Official Title
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An 8-Week, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Phase 3 Study of the Efficacy and Safety of Cariprazine in the Treatment of Pediatric Subjects (5 to 17 Years of Age) With Autism Spectrum Disorder

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Cariprazine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants at the time of screening must have a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of ASD, confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime (K-SADS-PL) administered at screening (Visit 1) by a trained clinician. Participants must have an Aberrant Behavior Checklist, 2nd edition - Community Version - Irritability (ABC-I) subscale score ≥ 18 (Visits 1 and 2). Participants must have a Clinical Global Impressions - Severity - Irritability (CGI-S Irritability) score ≥ 4 at screening (Visits 1 and 2). Exclusion Criteria: Participants with diagnosis of intellectual disability (Intelligence quotient < 25). No history of major depressive disorder, bipolar disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, or psychotic disorder due to another medical condition, as excluded by administration of Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime (K-SADS-PL). History of ASD that is associated with Rett Disorder, Fragile-X Syndrome, or Childhood Disintegrative Disorder.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

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: Cariprazine<br>Participants will receive age-and weight dependent flexible doses of cariprazine once daily for 8-weeks. | Drug: Cariprazine<br>* Oral Capsules or Oral Solution<br>* Other names: AGN-241780;|
| Placebo Comparator: Placebo<br>Participants will receive placebo once daily for 8-weeks. | Drug: Placebo<br>* Oral capsules or Oral Solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Aberrant Behavior Checklist, 2nd edition - Community Version - Irritability (ABC-I) Subscale Score | The Aberrant Behavior Checklist (ABC) - Community version is a 58-item, caregiver-rated scale designed to measure inappropriate and maladaptive behavior of people with developmental disabilities (including intellectual disability and ASD). The ABC has 5 subscales (Irritability, Social Withdrawal, Stereotypic Behavior, Hyperactivity and Inappropriate Speech). The caregiver rates the child's behavior from 0=not at all a problem to 3= the problem is severe in degree. The range for Irritability is 0 to 45. Higher scores indicate greater severity. | Baseline (Week 0) to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with responder status of Very Much Improved or Much Improved on the Clinical Global Impression- Change Irritability (CGI-C Irritability) Scale | The Clinical Global Impression - Change-Irritability (CGI-C Irritability) is a single-item rating scale that assesses change in the severity of a participant's irritability from the clinician's perspective. The CGI-C Irritability 7-point graded response scale (1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, or 7 = Very much worse). | Week 8 | 
| Change from Baseline in Parent-Rated Anxiety Scale for Youth with Autism Spectrum Disorder (PRAS-ASD) Total Score | PRAS-ASD is a 25-item caregiver-reported measure of anxiety in participants aged 3 to 17 with ASD. All items use a 4-point response scale: 0 = None (not present); 1 = Mild (present sometimes, not a real problem); 2 = Moderate (often present and a problem); 3 = Severe (very frequent and a major problem). Total score ranges from 0 to 75, with higher scores indicating greater severity of anxiety. | Baseline (Week 0) to Week 8 | 
| Change from Baseline in Caregiver Strain Questionnaire Short Form 7-Item (CGSQ SF-7) total score | CGSQ SF-7 is a caregiver-reported 7-item measure of self-reported strain that focuses on the impact of caring for a child with emotional and behavioral problems. Responses are scored on a 5-point scale (1 = Not at all, 2 = A little; 3 = Somewhat; 4 = Quite a bit; and 5 Very much) with higher scores indicating greater caregiver strain. | Baseline (Week 0) to Week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism Spectrum Disorder, Cariprazine, VRAYLAR, AGN-241780