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

• ClinicalTrials.gov Identifier: NCT03664232
• Recruitment Status: Completed
• First Posted: September 10, 2018
• Last Update Posted: December 8, 2022
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Autism Spectrum Disorder	Drug: JNJ-42165279; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 78 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 7, 2018
• Actual Primary Completion Date: October 17, 2022
• Actual Study Completion Date: October 28, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: JNJ-42165279; Participants will self-administer 25 milligram (mg) JNJ-42165279 tablets orally twice daily for 12 weeks.	Drug: JNJ-42165279; Participants will receive 25 mg JNJ-42165279 orally twice daily for 12 weeks.
Placebo Comparator: Placebo; Participants will self-administer matching placebo tablets orally twice daily for 12 weeks.	Drug: Placebo; Participants will receive a matching placebo orally twice daily for 12 weeks.

Outcome Measures

Primary Outcome Measures :

1. Change from Baseline in the Autism Behavior Inventory (ABI) Core Domain Score to Day 85 [ Time Frame: Baseline up 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.
2. Change from Baseline in ABI Social Communication Domain Score to Day 85 [ Time Frame: Baseline up 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.
3. Change from Baseline in ABI Repetitive/Restrictive Behavior (RRB) Domain Score to Day 85 [ Time Frame: Baseline up 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.

Secondary Outcome Measures :

1. Change from Baseline in the ABI Mood and Anxiety Domain Score to Day 85 [ Time Frame: Baseline up 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).
2. Change from Baseline in the ABI Challenging Behavior Domain Score [ Time Frame: Baseline up to Day 85 ]
   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).
3. Change from Baseline in the ABI Self-Regulation Domain Score [ Time Frame: Baseline up to Day 85 ]
   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).
4. Change from Baseline in the Aberrant Behavior Checklist (ABC) Subscales [ Time Frame: Baseline up to Day 85 ]
   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]).
5. Change from Baseline in the Autism Behavior Inventory-Short Form (ABI-S) Scale Domains [ Time Frame: Baseline up to Day 85 ]
   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]).
6. Change from Baseline in the Autism Behavior Inventory-Clinician Interview (ABI-C) Domains [ Time Frame: Baseline up to Day 85 ]
   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).
7. Change from Baseline in the Clinical Global Impression-Severity (CGI-S) Scale Score [ Time Frame: Baseline up to Day 85 ]
   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".
8. Change from Baseline in the Repetitive Behavior Scale - Revised (RBS-R) Scale Score [ Time Frame: Baseline up to Day 85 ]
   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.
9. Change from Baseline in the Zarit Burden Interview (ZBI) Scale Score [ Time Frame: Baseline up to Day 85 ]
   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.
10. Change from Baseline in the Child Adolescent Symptom Inventory - Anxiety (CASI-Anx) Scale Score [ Time Frame: Baseline up to Day 85 ]
    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.
11. Change from Baseline in the Social Responsiveness Scale 2 (SRS-2) Score [ Time Frame: Baseline up to Day 85 ]
    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.
12. Change from Baseline in the Caregiver Global Impression of Severity (Caregiver GI-S) [ Time Frame: Baseline up to Day 85 ]
    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.
13. Caregiver Assessment of Treatment Score [ Time Frame: Day 85 ]
    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).
14. Self Global Impression of Improvement (Self GI-I) Score [ Time Frame: Day 85 ]
    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.
15. Clinical Global Impression-Improvement (CGI-I) [ Time Frame: Day 85 ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 13 Years to 35 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Alabama

Harmonex Neuroscience Research

Dothan, Alabama, United States, 36303

United States, Arizona

Southwest Autism Research and Resource Center

Phoenix, Arizona, United States, 85006

United States, California

NRC Research Institute

Orange, California, United States, 92868

United States, New York

New York Presbyterian Hospital

New York, New York, United States, 10032

Nathan Kline Institute

Orangeburg, New York, United States, 10962

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

United States, Oklahoma

Cutting Edge Research Group

Oklahoma City, Oklahoma, United States, 73116

United States, Texas

BioBehavioral Research of Austin, PC

Austin, Texas, United States, 78759

United States, Washington

Seattle Children's Hospital

Seattle, Washington, United States, 98105

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

More Information

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT03664232
• Other Study ID Numbers: CR108275; 42165279AUT2001 ( Other Identifier: Janssen Research & Development, LLC )
• First Posted: September 10, 2018
• Last Update Posted: December 8, 2022
• Last Verified: December 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; JNJ-42165279; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action