A Phase II Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, and Tolerability of Arbaclofen Administered for the Treatment of Social Function in Children and Adolescents With Autism Spectrum Disorders: Study Protocol for AIMS-2-TRIALS-CT1

Mara Parellada, Antonia San José Cáceres, Melanie Palmer, Richard Delorme, Emily J H Jones, Jeremy R Parr, Evdokia Anagnostou, Declan G M Murphy, Eva Loth, Paul P Wang, Tony Charman, Andre Strydom, Celso Arango, Mara Parellada, Antonia San José Cáceres, Melanie Palmer, Richard Delorme, Emily J H Jones, Jeremy R Parr, Evdokia Anagnostou, Declan G M Murphy, Eva Loth, Paul P Wang, Tony Charman, Andre Strydom, Celso Arango

Abstract

Background: Autism Spectrum Disorder (ASD or autism) is characterized by difficulties in social communication and interaction, which negatively impact on individuals and their families' quality of life. Currently no pharmacological interventions have been shown to be effective for improving social communication in autism. Previous trials have indicated the potential of arbaclofen for improving social function among autistic children and adolescents with fluent speech. The AIMS2TRIALS-Clinical Trial 1 (AIMS-CT1) will examine whether arbaclofen is superior to placebo in improving social function and other secondary outcomes over 16 weeks, along with safety and tolerability profiles. Methods: AIMS-CT1 is an international, multi-site, double-blind, parallel group Phase II randomized clinical trial. It will include 130 males and females aged 5:0-17:11 years, with a diagnosis of ASD and fluent speech. Eligible participants will be randomized on a ratio of 1:1 for a 16-week treatment period. Medication will be titrated over 5 weeks. The primary outcome is the effect on social function from weeks 0 to 16 measured on the Socialization domain of the Vineland Adaptive Behavior Scales, 3rd editionTM. Secondary outcome measures include the CGI-S (Clinical Global Impression-Severity), CGI-I (Clinical Global Impression-Improvement), other areas of adaptive function, social communication and other autism symptoms, co-occurring behavior problems and health-related quality of life. Genetic and electrophysiological markers will be examined as potential stratifiers for treatment response. Exploratory novel digital technologies will also be used to measure change, examining simultaneously the validity of digital biomarkers in natural environments. The safety and tolerability of the drug will also be examined. Our protocol is very closely aligned with a parallel Canadian trial of 90 participants (ARBA Study, US NCT number: NCT03887676) to allow for secondary combined analyses. Outcomes will be compared using both an Intent-to-reat and Per Protocol approach. Discussion: The outcomes of this trial, combined with the parallel Canadian trial, will contribute to the evidence base for medications used to help social difficulties among young autistic individuals; demonstrate the capabilities of the AIMS-2-TRIALS network of academic centers to deliver clinical trials; and support future drug development. Clinical Trial Registration: EudraCT number: 2018-000942-21 and ClinicalTrials.gov registry number: NCT03682978. Currently under protocol v.7.2, dated 20.11.2020.

Keywords: adolescent; arbaclofen; autism; children; randomized controlled trial; social function.

Conflict of interest statement

MPar is consultant or has received honoraria or grants from for Exeltis and Servier. ASJ has served in an advisory or consultancy role for F. HoffmannLa Roche Ltd. and she is involved in clinical trials conducted by Servier. CC is a full-time employee of F. HoffmannLa Roche. PW was previously employed by Seaside Therapeutics and has served as an unpaid consultant for Roche. TC has received consultancy fees from F. Hoffmann-La Roche Ltd and Servier, and royalties from Sage Publications and Guilford Publications. DM has served on advisory boards for Roche and Servier. He has also received research funding from J+J. AS has consulted for AC Immune and Aelis Farma, and he is an advisory board member of ProMIS Neurosciences. CA has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion, and Takeda. EA has received consultation fees from Roche and Quadrant, research funding from Roche, in-kind supports from AMO pharma, editorial Honoria from Wiley and book royalties from APPI and Springer, she holds a patent for the device, “Tully” (formerly Anxiety Meter) and she has received royalties from APPI and Springer. DN is an employee of F. Hoffmann-LaRoche Ltd. ML is a consultant for F Hoffmann–La Roche Ltd. (Basel Switzerland) on behalf of Inovigate (Basel Switzerland). KB was previously employed by Seaside Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Parellada, San José Cáceres, Palmer, Delorme, Jones, Parr, Anagnostou, Murphy, Loth, Wang, Charman, Strydom and Arango.

Figures

Figure 1
Figure 1
CONSORT diagram showing trial and participant flow through the trial (based on CONSORT guidelines).

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