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

Janssen Research & Development, LLC78 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Autism Spectrum Disorder

Interventions

JNJ-42165279DRUG

Participants will receive 25 mg JNJ-42165279 orally twice daily for 12 weeks.

PlaceboDRUG

Participants will receive a matching placebo orally twice daily for 12 weeks.

Eligibility

Sex: ALLMin age: 13 YearsMax age: 35 Years

Medical Language ↔ Plain English

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

Locations (9)

Harmonex Neuroscience Research

Dothan, Alabama, United States

Southwest Autism Research and Resource Center

Phoenix, Arizona, United States

NRC Research Institute

Orange, California, United States

New York Presbyterian Hospital

Outcomes

Primary Outcomes

Change From Baseline to Day 85 in the Autism Behavior Inventory (ABI) Core Domain Score (Social Communication and Restrictive Behaviour)

ABI:62-item questionnaire to track outcomes in autism spectrum disorder (ASD). Each item was answered on 1 of 2 possible dimensions: quality (how well person carries out particular behavior; 1 to 13 items) or frequency (how often particular behavior occurs; 14 to 62 items). Each item was rated on scale of 0 (never) to 3 (very often) for frequency and 0 (without help) to 3 (not at all) for quality. Higher score=severe symptoms/more frequency. ABI core domain score was from 2 domains: social communication (23 items; 3 sub-domains) and repetitive/restrictive behavior (RRB;15 items; 4 sub-domains). Domain and sub-domain scores: calculated as average of non-missing items (ie, sum of all non-missing items divided by number of non-missing items); scores ranged from 0 to 3, higher scores=more severe symptoms of ASD. ABI core domain score=sum of social communication and RRB domain scores divided by total number of items in these 2 domains. Negative changes in ABI core domain score=improvement.

Time frame: Baseline (Day 1) to Day 85

Change From Baseline to Day 85 in the ABI Social Communication Domain Score

ABI was 62-item questionnaire completed on a web/mobile application or on paper. It tracks outcomes in ASD. Each ABI item was answered on 1 of 2 possible dimensions, quality (how well a person carries out a particular behavior; 1 to 13 items) or frequency (how often a particular behavior occurs; 14 to 62 items). Each item was rated on scale of 0 (never) to 3 (very often) for frequency and 0 (without help) to 3 (not at all) for quality. Higher score indicated severe symptoms/more frequency. The ABI social communication domain score consisted of 23 items; with 3 sub-domains. The domain and sub-domain scores were calculated as the average of the non-missing items (ie, sum of all non-missing items divided by the number of non-missing items). For both domains and its sub-domains, scores ranged from 0 to 3 with higher scores indicating more severe symptoms of ASD. Negative change in score indicates improvement.

Time frame: Baseline (Day 1) to Day 85

Change From Baseline to Day 85 in the ABI Repetitive/Restrictive Behavior (RRB) Domain Score

ABI is 62-item questionnaire completed on a web/mobile application or on paper. It tracks outcomes in ASD. Each ABI item was answered on 1 of 2 possible dimensions, quality (how well a person carries out a particular behavior; 1 to 13 items) or frequency (how often a particular behavior occurs; 14 to 62 items). Each item was rated on scale of 0 (never) to 3 (very often) for frequency and 0 (without help) to 3 (not at all) for quality. Higher score indicated severe symptoms/more frequency. The ABI RRB domain score consisted of 15 items; with 3 sub-domains. The domain and sub-domain scores were calculated as the average of the non-missing items (ie, sum of all non-missing items divided by the number of non-missing items). For both domains and its sub-domains, scores ranged from 0 to 3 with higher scores indicating more severe symptoms of ASD. Negative change in score indicates improvement.

Data from ClinicalTrials.gov

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Secondary Outcomes

Change From Baseline to Day 85 in the ABI Mood and Anxiety Domain Score

ABI was 62-item questionnaire to track outcomes in ASD. Each ABI item was answered on 1 of 2 possible dimensions, quality (how well a person carries out a particular behavior; 1 to 13 items) or frequency (how often a particular behavior occurs; 14 to 62 items). Each item was rated on scale of 0 (never) to 3 (very often) for frequency and 0 (without help) to 3 (not at all) for quality. Higher score indicated severe symptoms/more frequency. ABI mood and anxiety domain had 9 items with 5 sub-domains. ABI mood and anxiety domain and its sub-domains, scores ranged from 0 to 3 with higher scores indicating more severe symptoms of ASD. Domain and sub-domain scores were calculated as the average of the non-missing items (ie, sum of all non-missing items divided by the number of non-missing items). Negative changes in ABI mood and anxiety domain score indicated improvement.

Time frame: Baseline (Day 1) to Day 85

Change From Baseline to Day 85 in the ABI Challenging Behavior Domain Score

ABI was 62-item questionnaire to track outcomes in ASD. Each ABI item was answered on 1 of 2 possible dimensions, quality (how well a person carries out a particular behavior; 1 to 13 items) or frequency (how often a particular behavior occurs; 14 to 62 items). Each item was rated on scale of 0 (never) to 3 (very often) for frequency and 0 (without help) to 3 (not at all) for quality. Higher score indicated severe symptoms/more frequency. ABI challenging behavior domain had 7 items with 4 sub-domains. ABI challenging behavior domain and its sub-domains, scores ranged from 0 to 3 with higher scores indicating more severe symptoms of ASD. The domain and sub-domain scores were calculated as the average of the non-missing items (ie, sum of all non-missing items divided by the number of non-missing items). Negative changes in ABI challenging behavior domain score indicated improvement.

Time frame: Baseline (Day 1) to Day 85

Change From Baseline to Day 85 in the ABI Self-Regulation Domain Score

ABI was 62-item questionnaire to track outcomes in ASD. Each ABI item was answered on 1 of 2 possible dimensions, quality (how well a person carries out a particular behavior; 1 to 13 items) or frequency (how often a particular behavior occurs; 14 to 62 items). Each item was rated on scale of 0 (never) to 3 (very often) for frequency and 0 (without help) to 3 (not at all) for quality. Higher score indicated severe symptoms/more frequency. ABI self-regulation domain had 8 items with 2 sub-domains. ABI self-regulation domain and its sub-domains, scores ranged from 0 to 3 with higher scores indicating more severe symptoms of ASD. The domain and sub-domain scores were calculated as the average of the non-missing items (ie, sum of all non-missing items divided by the number of non-missing items). Negative changes in ABI self-regulation domain score indicated improvement.

Time frame: Baseline (Day 1) to Day 85

Change From Baseline to Day 85 in the Aberrant Behavior Checklist (ABC) Subscales Scores

The ABC was 58-item behavior rating scale used to measure behavior problems across 5 subscales: irritability (15 items), lethargy (social withdrawal; 16 items), stereotypic behavior (7 items), hyperactivity/ noncompliance (16 items), and inappropriate speech (4 items). Items were rated on a 4-point scale score ranging from 0 (not at all a problem) to 3 (the problem is severe in degree). The total subscale scores ranged from 0 to 45, 0 to 48, 0 to 21, 0 to 48 and 0 to 12 for irritability, lethargy (social withdrawal), stereotypic behavior, hyperactivity, and inappropriate speech respectively. The higher scores indicating more severe behavior problems. Negative change in score indicated improvement.

Time frame: Baseline (Day 1) to Day 85

Change From Baseline to Day 71 in the Autism Behavior Inventory-Short Form (ABI-S) Domains Scores

The ABI-S was the shorter version of ABI. It consists of 24 items across 5 areas: challenging behavior (3 items), mood and anxiety (5 items), restrictive behaviors (7 items), social communication (6 items), and self-regulation (3 items). Each item was 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 ABI-S domain score was calculated as the sum of the scores in the ABI-S domain divided by the total number of items in this domain. Each item was rated on scales of 0 (never) to 3 (very often) for frequency and 0 (without help) to 3 (not at all) for quality. The total subscale scores ranged from 0 to 9, 0 to 15, 0 to 21, 0 to 18, and 0 to 9, for challenging behavior, mood and anxiety, restrictive behaviors, social communication, and self-regulation respectively. Lower score indicated better performance. Negative change in score indicates improvement.

Time frame: Baseline (Day 1) to Day 71

Change From Baseline to Day 85 in the Autism Behavior Inventory-Clinician Interview (ABI-C) Domains Scores

The ABI-C covers the domains of ABI and was intended for completion by the clinician following an interview with caregiver and observation or interview with the individual with ASD, as appropriate. The ABI-C was designed to capture the behaviors of a person with ASD that have occurred over the past week. There were 14 items across each of the 5 domains: challenging behavior (2 items), mood and anxiety (2 items), restrictive behaviors (5 items), social communication (3 items), and self-regulation (2 items). The clinician rates the severity of behaviors or level of impairment on a scale of 1 (no impairment) to 7 (very severe difficulties) with a higher score indicating more severe symptoms of ASD. Total subscale scores ranged from 0 to 14, 0 to 14, 0 to 35, 0 to 21 and 0 to 14, for challenging behavior, mood and anxiety, restrictive behaviors, social communication and self-regulation respectively. Lower score indicated better performance. Negative change in score indicates improvement.

Time frame: Baseline (Day 1) to Day 85

Change From Baseline to Day 85 in the Clinical Global Impression-Severity (CGI-S) Scale Score

The CGI-S 7-point scale was a global assessment that measures the clinician's impression of the severity of illness of the participant. A rating scale of 1 to 7 was used, with 1="normal, not at all ill" and 7="among the most extremely ill". Higher score indicated more severe illness.

Time frame: Baseline (Day 1) to Day 85

Change From Baseline to Day 85 in the Repetitive Behavior Scale - Revised (RBS-R) Subscale Score

The RBS-R was a 43-item report scale to indicate the occurrence of repetitive behaviors and degree to which a behavior was a problem scored on a range between 0 (behavior did not occur) to 3 (behavior occurred and was a severe problem). There are 6 subscale scores: Stereotyped Behavior (items 1 to 6), self-injurious behavior (items 7 to 14), compulsive behavior (items 15 to 22), ritualistic behavior (items 23 to 28), sameness behavior (items 29 to 39), and restricted behavior (items 40 to 43). The ranges for RBS-R subscale scores were stereotyped behavior: 0 to 18; self-injurious behavior: 0 to 24; compulsive behavior: 0 to 24; ritualistic behavior: 0 to 18; sameness behavior: 0 to 33; and restricted behavior: 0 to 12. Higher scores indicate more severe problems with repetitive behaviors and a decrease (a negative change) from baseline represents improvement.

Time frame: Baseline (Day 1) to Day 85

Change From Baseline to Day 85 in the Zarit Burden Interview (ZBI) Global Score

The ZBI short version scale consists of 22 items designed to assess the psychological burden experienced by a caregiver. Items ask how the caregiver felt and their responses range from 0 to 4, where 0 = never and 4 = nearly always. The ZBI global score was the sum of all item score and ranges from 0 to 88 with higher scores indicating a higher burden. A negative change in the ZBI global score from baseline representing improvement.

Time frame: Baseline (Day 1) to Day 85

Change From Baseline to Day 85 in the Child Adolescent Symptom Inventory - Anxiety (CASI-Anx) Scale Score

The CASI assesses symptoms of the following disorders: attention deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder, generalized anxiety disorder, social phobia, separation anxiety disorder, disruptive mood dysregulation disorder, major depressive episode, manic episode, dysthymic disorder, schizophrenia, autistic/Asperger's disorder, anorexia, and bulimia. CASI-Anx scale total is a 21-point anxiety subscale of the full CASI. Responses were ranged from 0 to 3, where 0 = never and 3 = very often. The CASI-Anx scale total score ranges from 0 to 63 with higher scores indicating more severe anxiety. Negative changes in Symptom Severity scores indicate improvement.

Time frame: Baseline (Day 1) to Day 85

Change From Baseline to Day 85 in the Caregiver Global Impression of Severity (Caregiver GI-S) Scale Score

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. A rating scale of 1 to 7 was used, with 1= none and 7=severe illness. Higher score indicated more severe illness.

Time frame: Baseline (Day 1) to Day 85

Caregiver Assessment of Treatment: Question 1: Number of Participants With Overall Status (Improvement) of Autism at Day 85

The caregiver assessment of treatment is a 3-item questionnaire completed at the end of the treatment period. The first question asks caregivers to rate their overall impression of improvement in their child's autism since starting the study medication, with 7 response options ranging from 1 "very much improved" to 7 "very much worse".

Time frame: At Day 85

Caregiver Assessment of Treatment: Question 2: Number of Participants With Improvement in Specific Symptoms During Treatment at Day 85

The caregiver assessment of treatment was a 3-item questionnaire completed at the end of the treatment period. The second question asks caregivers whether there was improvement in 9 specific symptoms (child communicated more, child's repetitive behaviors improvement, child's restricted interests, child's mood improved, child was less anxious, child better perform daily activities, child more interest social activities, child's sleep improved, child less distracted), with responses options of Yes or No.

Time frame: At Day 85

Caregiver Assessment of Treatment: Question 3: Number of Participants With Interest in Continuing Treatment at Day 85

The caregiver assessment of treatment is a 3-item questionnaire completed at the end of the treatment period. The third question asked caregivers their interest in having their child continue the study medication. There were 5 response options ranging from "Not at all interested" to "Extremely interested".

Time frame: At Day 85

Self Global Impression of Improvement (Self GI-I) Scale Score at Day 85

Self-Global impression of improvement (Self GI-I) scale score at Day 85 was reported. At the end of the treatment period, the participant was asked to give his/her impression of overall improvement in ASD symptoms using a single-item instrument, the Self GI-I. The scale ranges from 1 (very much better) to 7 (very much worse), with higher scores indicating worsening of symptoms.

Time frame: At Day 85

Clinical Global Impression-Improvement (CGI-I) Score (Frequency Distribution) at Day 85

The CGI-I was single-item instrument that measures the clinician's global impression of improvement in the participant from the initiation of treatment. The CGI-I was 7-point scale to measure improvement in illness, where 1=very much improved, 2=much improved, 3=minimally improved, 4=no change from baseline, 5=minimally worse, 6=much worse, 7=very much worse.

Time frame: At Day 85