A Study to Investigate the Efficacy, Safety, and Tolerability of JNJ-42165279 in Adolescent and Adult Participants With Autism Spectrum Disorder

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of JNJ-42165279 compared with placebo in the improvement of symptoms of Autism Spectrum Disorder (ASD) during 12 weeks of treatment using the Autism Behavior Inventory (ABI).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multicenter Study Investigating the Efficacy, Safety, and Tolerability of JNJ-42165279 in Adolescent and Adult Subjects With Autism Spectrum Disorder

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Drug: JNJ-42165279
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Autism Spectrum Disorder (ASD) according to Diagnostic and Statistical Manual of Mental Disorders - 5th Edition (DSM-5) criteria and made or confirmed using the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) (minimum score of 8 [autism spectrum]) Otherwise healthy for their age group or medically stable with or without medication on the basis of physical examination, medical history, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests Have a composite score on Kaufman Brief Intelligence Test, Second Edition (KBIT-2) of at least 60 Must live with a parent or primary caregiver or, if not, during each week he/she must either (A) spend at least 3 hours a day for at least 4 days or, (B) spend the weekend with a parent or primary caregiver Any pharmacologic, diet, or behavioral intervention for ASD must have begun at least 1 month prior to the baseline visit and continue unchanged through the treatment period, or have ended at least 1 month prior to the baseline visit Must be able to swallow the study medication whole and self-administer medication if living independently or have a parent or caregiver be able to administer medication Must agree to abide by the birth control requirements during the study and for 3 months after the last dose Exclusion Criteria: Current or recent history of clinically significant suicidal ideation within the past 6 months, or a history of suicidal behavior within the past year Use of a drug with moderate/strong cytochrome P450 (CYP)3A4 inhibiting or inducing properties at, or prior to, screening that is not discontinued at least within 1 month prior to Day 1 History of drug or alcohol use disorder according to DSM-5 criteria within 6 months before screening or positive test result(s) for alcohol or drugs of abuse (except if related to current treatment) Currently taking or has taken within the past month recreational or medically prescribed cannabis

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 35 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JNJ-42165279<br>Participants will self-administer 25 milligram (mg) JNJ-42165279 tablets orally twice daily for 12 weeks. | Drug: JNJ-42165279<br>* Participants will receive 25 mg JNJ-42165279 orally twice daily for 12 weeks.<br>|
| Placebo Comparator: Placebo<br>Participants will self-administer matching placebo tablets orally twice daily for 12 weeks. | Drug: Placebo<br>* Participants will receive a matching placebo orally twice daily for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the Autism Behavior Inventory (ABI) Core Domain Score to Day 85 | Change from baseline in the ABI core domain score will be reported. ABI is a 62-item questionnaire completed on a web/mobile application or on paper. It is part of the Janssen Autism Knowledge Engine (JAKE), a research tool that tracks outcomes in Autism Spectrum Disorder (ASD). Each ABI item is answered on 1 of 2 possible dimensions, quality (how well a person carries out a particular behavior) or frequency (how often a particular behavior occurs). Each item is rated on a scale of 0-3 (never to very often [frequency] or not at all to without help [quality]). The ABI Core Domain Score is calculated as the sum of the scores in the Social Communication Domain and the Repetitive/Restrictive Behavior Domain divided by the total number of items in these 2 domains. | Baseline up to Day 85 | 
| Change from Baseline in ABI Social Communication Domain Score to Day 85 | Change from baseline in the ABI social communication domain score will be reported. Each item is rated on a scale of 0-3 (never to very often [frequency] or not at all to without help [quality]). The ABI social communication domain score is calculated as the sum of the scores in the social communication domain divided by the total number of items in this domain. | Baseline up to Day 85 | 
| Change from Baseline in ABI Repetitive/Restrictive Behavior (RRB) Domain Score to Day 85 | Change from baseline in the ABI RRB domain score will be reported. Each item is rated on a scale of 0-3 (never to very often). The ABI RRB domain score is calculated as the sum of the scores in the RRB domain divided by the total number of items in this domain. | Baseline up to Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in the ABI Mood and Anxiety Domain Score to Day 85 | Change from baseline in the ABI mood and anxiety domain score will be reported. The ABI mood and anxiety domain score is calculated as the sum of the scores in the mood and anxiety domain divided by the total number of items in this domain. Each item is rated on a scale of 0-3 (never to very often). | Baseline up to Day 85 | 
| Change from Baseline in the ABI Challenging Behavior Domain Score | Change from baseline in the ABI challenging behavior domain score will be reported. The ABI challenging behavior domain score is calculated as the sum of the scores in the challenging behavior domain divided by the total number of items in this domain. Each item is rated on a scale of 0-3 (never to very often). | Baseline up to Day 85 | 
| Change from Baseline in the ABI Self-Regulation Domain Score | Change from baseline in the ABI self-regulation domain score will be reported. The ABI self-regulation domain score is calculated as the sum of the scores in the self-regulation domain divided by the total number of items in this domain. Each item is rated on a scale of 0-3 (never to very often). | Baseline up to Day 85 | 
| Change from Baseline in the Aberrant Behavior Checklist (ABC) Subscales | Change from baseline in the ABC subscales will be reported. The ABC is a 58-item behavior rating scale used to measure behavior problems across 5 subscales: Irritability, Lethargy (Social Withdrawal), Stereotypy, Hyperactivity, Inappropriate Speech. Items are rated on a 4-point scale (ranging from 0 [not at all a problem] to 3 [the problem is severe in degree]). | Baseline up to Day 85 | 
| Change from Baseline in the Autism Behavior Inventory-Short Form (ABI-S) Scale Domains | Change from baseline in the ABI-S scale domains will be reported. ABI-S is the shorter version of the ABI. It consists of 24 items across 5 areas, social communication, RRB, mood and anxiety, challenging behavior, and self-regulation. Each ABI-S domain score is calculated as the sum of the scores in the ABI-S domain divided by the total number of items in this domain. Each item is rated on a scale of 0-3 (never to very often [frequency] or not at all to without help [quality]). | Baseline up to Day 85 | 
| Change from Baseline in the Autism Behavior Inventory-Clinician Interview (ABI-C) Domains | Change from baseline in the ABI-C domains will be reported. The ABI-C is designed to capture the behaviors of a person with ASD that have occurred over the past week. There are 14 items across each of the 5 domains (social communication, restrictive behaviors, mood and anxiety, self regulation and challenging behavior). The clinician rates the severity of behaviors and level of impairment on a scale of 1 (none) to 7 (very severe). | Baseline up to Day 85 | 
| Change from Baseline in the Clinical Global Impression-Severity (CGI-S) Scale Score | Change from baseline in the CGI-S scale score will be reported. The CGI-S rating scale is a global assessment that measures the clinician's impression of the severity of illness of the participant. A rating scale of 1-7 is used, with 1=normal, not at all ill and 7=among the most extremely ill. | Baseline up to Day 85 | 
| Change from Baseline in the Repetitive Behavior Scale - Revised (RBS-R) Scale Score | Change from baseline in the RBS-R scale score will be reported. The RBS-R is a 43-item rating scale to indicate occurrence of repetitive behaviors and degree to which a behavior is a problem on a range between 0 to 3, where 0 = behavior does not occur and 3 = behavior occurs and is a severe problem. | Baseline up to Day 85 | 
| Change from Baseline in the Zarit Burden Interview (ZBI) Scale Score | Change from baseline in the ZBI scale score will be reported. The ZBI short version scale consists of 22 items designed to assess the psychological burden experienced by a caregiver. Responses range from 0-4, where 0 = never and 4 = nearly always. | Baseline up to Day 85 | 
| Change from Baseline in the Child Adolescent Symptom Inventory - Anxiety (CASI-Anx) Scale Score | Change from baseline in the CASI-Anx scale score will be reported. CASI-Anx is a 21-point anxiety subscale of the full CASI. Responses will range from 0 to 3, where 0 = never and 3 = very often. | Baseline up to Day 85 | 
| Change from Baseline in the Social Responsiveness Scale 2 (SRS-2) Score | Change from baseline in the SRS-2 scale score will be reported. The SRS-2 is a 65-item scale that measures social impairment and includes 5 subscales. Responses range from 1 to 4, where 1 = Not true and 4 = almost always true. | Baseline up to Day 85 | 
| Change from Baseline in the Caregiver Global Impression of Severity (Caregiver GI-S) | Change from baseline in the Caregiver GI-S scale score will be reported. The Caregiver GI-S is a single-item instrument that asks caregivers to rate their overall impression of the severity of their child's ASD symptoms. Responses range from 1 to 7, where 1 = None and 7 = Severe. | Baseline up to Day 85 | 
| Caregiver Assessment of Treatment Score | The Caregiver Assessment of Treatment is a 3-item questionnaire. Caregivers rate their global impression of improvement in their child's autism, whether there was improvement in specific symptoms, and their interest in having their child continue the study medication. One item uses a scale of 1 (very much improved) to 7 (very much worse), another item includes a Yes/No checklist, and another item uses a scale of 1 (not at all interested) to 5 (extremely interested). | Day 85 | 
| Self Global Impression of Improvement (Self GI-I) Score | The participant will be asked to give his/her impression of overall improvement in ASD symptoms using a single-item instrument, the Self GI-I. Responses will range from 1 to 7, where 1 = Very much better and 7 = Very much worse. | Day 85 | 
| Clinical Global Impression-Improvement (CGI-I) | The CGI-I is a single-item instrument that measures the clinician's global impression of improvement in the participant from the initiation of treatment. A 7-point scale is used, with 1=very much improved and 7=very much worse. | Day 85 |