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Lookup NU author(s): Dr Helen Leonard, Naomi White
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© 2026 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC license. http://creativecommons.org/licenses/by-nc/4.0/SummaryBackgroundPrevious trials have indicated the potential of arbaclofen for improving social difficulties among autistic children and adolescents with fluent speech. AIMS-2-TRIALS-Clinical Trial 1 (AIMS-2-CT1) examined whether arbaclofen is superior to placebo in improving social function and other secondary outcomes, along with safety and tolerability profiles.MethodsAIMS-2-CT1 is a multi-site, placebo-controlled double-blind, parallel group Phase II randomized clinical trial. Recruitment was conducted in 7 sites in Spain, United Kingdom and France between September 2019 and September 2022. Eligible participants were randomized 1:1, stratified by age and site, for a 16-week treatment period. Age of participants ranged from 5 to 17 years of age. Primary outcome: Socialization domain of the Vineland Adaptive Behavior Scales change. Secondary outcome measures: CGI–S (Clinical Global Impression–Severity), CGI–I (Clinical Global Impression–Improvement), Social Responsiveness Scale (SRS-2), Autism Impact Measure (AIM), behavioral measurements (CBCL, ABC-C) and Quality of Life (PedsQL). Safety and tolerability were assessed via several instruments. Clinical trial registration: EudraCT number: 2018-000942-21 and ClinicalTrials.gov registry number: NCT03682978. Last protocol v.9.1, dated June 18th, 2022.Findings122 participants (out of 123 randomized) comprised the Intention-to-treat sample (59/63 arbaclofen/placebo); 85%/95% of participants on arbaclofen/placebo completed the study.Improvements in the primary endpoint and pre-specified key secondary outcomes did not achieve statistical significance [effect size 1.30 (95% CI: −2.6, 5.1)]. Results on all secondary endpoints favored arbaclofen, with significant improvements on many secondary outcomes including the SRS, the AIM Total scores, some subscales of the ABC, and QoL measures. One Serious Adverse Event (psychotic symptoms) was reported on placebo. Sleep-related problems were more frequent on arbaclofen (N = 34, 57.6% in participants on arbaclofen and N = 22, 34.9% in participants on placebo).InterpretationAlthough we found no significant effect on the primary outcome, improvements were apparent on several secondary measures of autistic related behaviors as well as quality of life. Arbaclofen shows promise in addressing some autistic difficulties and in improving quality of life, but larger scale trials are needed to further advance our understanding of its potential and to inform future drug development in autism.FundingInnovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394.
Author(s): Parellada M, San Jose Caceres A, Delorme R, Moscoso A, Moreno C, Calvo R, Canal-Bedia R, Franco Martin MA, Charman T, Strydom A, Parr JR, Urbiola Merino E, Burdeus-Olavarrieta M, Hernandez Jusdado P, Solis A, Lucas M, Sipos L, Gonzalez Navarro P, Blazquez A, Lazaro L, Tomas A, Humeau E, Antoun S, Cooke J, Megalogeni M, Liang H, de-Vena-Diez VB, Leonard H, White N, Wang P, Walton-Bowen K, Winter-van Rossum I, Murphy D, Arango C
Publication type: Article
Publication status: Published
Journal: eClinicalMedicine
Year: 2026
Volume: 92
Online publication date: 22/01/2026
Acceptance date: 06/01/2026
Date deposited: 15/04/2026
ISSN (electronic): 2589-5370
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.eclinm.2026.103760
DOI: 10.1016/j.eclinm.2026.103760
Data Access Statement: We adopt a curated data-sharing approach, meaning that direct access to the data is limited to the study investigators. Other researchers interested in using this data must apply for access by submitting a brief research scope and a motivation letter, detailing the intended purpose of the data, via email to the corresponding author. Data will be made available upon reasonable request. Note that sharing of pseudonymized personal data will require a data-sharing agreement, according to EU law.
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