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Efficacy and safety of JNJ-42165279, a fatty acid amide hydrolase inhibitor, in adolescents and adults with autism spectrum disorder: a randomized, phase 2, placebo-controlled study

Neuropsychopharmacology volume 50, pages 480–487 (2025)Cite this article

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A Correction to this article was published on 31 January 2025

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Abstract

JNJ-42165279, a highly selective and orally bioavailable fatty acid amide (FAA) hydrolase inhibitor, was evaluated for efficacy and safety in adolescents and adults with autism spectrum disorder (ASD) in this phase 2, double-blind, placebo-controlled, multicenter study (NCT03664232). Participants aged 13–35 years, with a diagnosis of ASD (Diagnostic and Statistical Manual of Mental Disorders, 5th edition; Autism Diagnostic Observation Schedule, 2nd edition) were randomized (1:1) to 12 weeks of treatment with JNJ-42165279 (25 mg, twice-daily) or placebo. Primary endpoints were the change in the Autism Behavior Inventory (ABI) Core Domain (ABI-CD), ABI-Social Communication (ABI-SC), and ABI-Repetitive/Restrictive Behavior (ABI-RB) scores from baseline to day 85. Of the 61 participants (16 female, 45 male) included in the efficacy analyses, 53 (87%) completed the double-blind treatment. At day 85, the JNJ-42165279 group did not show a statistically significant reduction in ASD symptoms versus placebo, as assessed with ABI-CD (p = 0.284), ABI-SC (p = 0.290), and ABI-RB (p = 0.231). However, the following secondary outcomes exhibited small to moderate changes directionally favoring JNJ-42165279: Social Responsiveness Scale 2 (SRS, p = 0.064), Repetitive Behavior Scale-Revised (RBS-R, p = 0.006), Zarit Burden Interview short version (ZBI, p = 0.063), Child Adolescent Symptom Inventory-Anxiety (CASI-Anx, p = 0.048), and Caregiver Global Impression of Severity (p = 0.075). Notably, versus placebo, JNJ-42165279-treated participants showed increased concentrations of FAAs throughout the treatment period, with those achieving elevated concentrations experiencing the greatest reduction in the SRS total score at day 85. JNJ-42165279 demonstrated an acceptable safety profile. Although primary endpoints were not met, JNJ-42165279 may have a therapeutic effect on certain aspects of core ASD symptoms.

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Fig. 1: LS Mean (±SE) Change from baseline over time in autism behavior inventory core domain score (Observed Case).
Fig. 2: Forest plot of least squares mean changes from baseline to day 85 in the secondary endpoints.
Fig. 3: Social responsiveness scale 2 Total T-score: Arithmetic Mean (±SE) Over Time (Observed Case).

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Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files. The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access [YODA] Project site at http://yoda.yale.edu.

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Acknowledgements

The authors acknowledge Vaibhav Deshpande, PhD and Himabindu Gutha, PhD, CMPP (SIRO Clinpharm Pvt. Ltd.) for providing writing assistance, which was funded by Janssen Global Services, LLC. Ellen Baum, PhD (Janssen Global Services, LLC) for additional editorial support for this manuscript. We thank Seth Ness, MD, PhD for his commitment to this study including conception design, and implementation. We also want to express our gratitude and acknowledge the passing of Sandra Chaplan, MD (Study Physician) and Marlene Ball (Trial Manager), who played vital roles in this study.

Funding

The studies presented in this report were supported by Janssen Research & Development, LLC.

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Authors and Affiliations

  1. Janssen Research & Development, LLC, San Diego, CA, USA

    Matthew E. Klein, Robin J. Halter, Zuleima Aguilar & Wayne C. Drevets

  2. Janssen Research & Development, LLC, Titusville, NJ, USA

    Abigail Bangerter, Carla M. Canuso, Mark E. Schmidt & Gahan Pandina

  3. Janssen Research & Development, LLC, Spring House, PA, USA

    Kim Cooper

  4. Janssen Pharmaceutica NV, Beerse, Belgium

    Mark E. Schmidt

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Contributions

MK: Study conduct, analysis, and interpretation. AB: Study design, conduct, analysis, and interpretation. KC: Formal Analysis. RH: Study design, conduct, analysis, and interpretation. ZA: Study design, conduct, analysis, and interpretation. CC: Study design, conduct, analysis, and interpretation. WD: Study design, conduct, analysis, and interpretation. MS: Safety monitoring, protocol review. GP: Study design, conduct, analysis, and interpretation. All authors participated in the writing and revising of this manuscript and approved the final manuscript content to be submitted to the journal.

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Correspondence to Matthew E. Klein.

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Klein, M.E., Bangerter, A., Halter, R.J. et al. Efficacy and safety of JNJ-42165279, a fatty acid amide hydrolase inhibitor, in adolescents and adults with autism spectrum disorder: a randomized, phase 2, placebo-controlled study. Neuropsychopharmacol. 50, 480–487 (2025). https://doi.org/10.1038/s41386-024-02001-2

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