Efficacy, safety, and tolerability of arbaclofen in Autistic children and adolescents, the AIMS-2-TRIALS-CT1: a randomized, double-blind, placebo-controlled phase II trial

M Parellada; A San José Cáceres; R Delorme; A Moscoso; C Moreno; R Calvo; R Canal-Bedia; M A Franco Martín; T Charman; A Strydom; J R Parr; E Urbiola Merino; M Burdeus-Olavarrieta; P Hernández Jusdado; A Solis; M Lucas; L Sipos; P González Navarro; A Blázquez; L Lázaro; A Tomás; E Humeau; S Antoun; J Cooke; M Megalogeni; H Liang; V B de-Vena-Díez; H Leonard; N White; P Wang; K Walton-Bowen; I Winter-van Rossum; D Murphy; C Arango

doi:10.1016/j.eclinm.2026.103760

Efficacy, safety, and tolerability of arbaclofen in Autistic children and adolescents, the AIMS-2-TRIALS-CT1: a randomized, double-blind, placebo-controlled phase II trial

M Parellada^*
, A San José Cáceres
, R Delorme
, A Moscoso
, C Moreno
, R Calvo
, R Canal-Bedia
, M A Franco Martín
, T Charman
, A Strydom
, J R Parr
, E Urbiola Merino
, M Burdeus-Olavarrieta
, P Hernández Jusdado
, A Solis
, M Lucas
, L Sipos
, P González Navarro
, A Blázquez
, L Lázaro

A Tomás, E Humeau, S Antoun, J Cooke, M Megalogeni, H Liang, V B de-Vena-Díez, H Leonard, N White, P Wang, K Walton-Bowen, I Winter-van Rossum, D Murphy, C Arango

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Previous 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.

METHODS: AIMS-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.

FINDINGS: 122 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).

INTERPRETATION: Although 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.

FUNDING: Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394.

Original language	English
Article number	103760
Journal	EClinicalMedicine
Volume	92
DOIs	https://doi.org/10.1016/j.eclinm.2026.103760
Publication status	Published - Feb 2026

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Efficacy, safety, and tolerability of arbaclofen in Autistic children and adolescents, the AIMS-2-TRIALS-CT1: a randomized, double-blind, placebo-controlled phase II trialFinal published version, 1.47 MBLicence: CC BY-NC

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Parellada, M., San José Cáceres, A., Delorme, R., Moscoso, A., Moreno, C., Calvo, R., Canal-Bedia, R., Franco Martín, M. A., Charman, T., Strydom, A., Parr, J. R., Urbiola Merino, E., Burdeus-Olavarrieta, M., Hernández Jusdado, P., Solis, A., Lucas, M., Sipos, L., González Navarro, P., Blázquez, A., ... Arango, C. (2026). Efficacy, safety, and tolerability of arbaclofen in Autistic children and adolescents, the AIMS-2-TRIALS-CT1: a randomized, double-blind, placebo-controlled phase II trial. EClinicalMedicine, 92, Article 103760. https://doi.org/10.1016/j.eclinm.2026.103760

@article{ab09a74201294a87b04a8b3c0fcf64fd,

title = "Efficacy, safety, and tolerability of arbaclofen in Autistic children and adolescents, the AIMS-2-TRIALS-CT1: a randomized, double-blind, placebo-controlled phase II trial",

abstract = "BACKGROUND: Previous 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.METHODS: AIMS-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.FINDINGS: 122 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).INTERPRETATION: Although 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.FUNDING: Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394.",

author = "M Parellada and \{San Jos{\'e} C{\'a}ceres\}, A and R Delorme and A Moscoso and C Moreno and R Calvo and R Canal-Bedia and \{Franco Mart{\'i}n\}, \{M A\} and T Charman and A Strydom and Parr, \{J R\} and \{Urbiola Merino\}, E and M Burdeus-Olavarrieta and \{Hern{\'a}ndez Jusdado\}, P and A Solis and M Lucas and L Sipos and \{Gonz{\'a}lez Navarro\}, P and A Bl{\'a}zquez and L L{\'a}zaro and A Tom{\'a}s and E Humeau and S Antoun and J Cooke and M Megalogeni and H Liang and de-Vena-D{\'i}ez, \{V B\} and H Leonard and N White and P Wang and K Walton-Bowen and \{Winter-van Rossum\}, I and D Murphy and C Arango",

note = "{\textcopyright} 2026 The Authors. Published by Elsevier Ltd.",

year = "2026",

month = feb,

doi = "10.1016/j.eclinm.2026.103760",

language = "English",

volume = "92",

journal = "EClinicalMedicine",

issn = "2589-5370",

publisher = "Elsevier Limited",

}

Parellada, M, San José Cáceres, A, Delorme, R, Moscoso, A, Moreno, C, Calvo, R, Canal-Bedia, R, Franco Martín, MA, Charman, T, Strydom, A, Parr, JR, Urbiola Merino, E, Burdeus-Olavarrieta, M, Hernández Jusdado, P, Solis, A, Lucas, M, Sipos, L, González Navarro, P, Blázquez, A, Lázaro, L, Tomás, A, Humeau, E, Antoun, S, Cooke, J, Megalogeni, M, Liang, H, de-Vena-Díez, VB, Leonard, H, White, N, Wang, P, Walton-Bowen, K, Winter-van Rossum, I, Murphy, D & Arango, C 2026, 'Efficacy, safety, and tolerability of arbaclofen in Autistic children and adolescents, the AIMS-2-TRIALS-CT1: a randomized, double-blind, placebo-controlled phase II trial', EClinicalMedicine, vol. 92, 103760. https://doi.org/10.1016/j.eclinm.2026.103760

TY - JOUR

T1 - Efficacy, safety, and tolerability of arbaclofen in Autistic children and adolescents, the AIMS-2-TRIALS-CT1

T2 - a randomized, double-blind, placebo-controlled phase II trial

AU - Parellada, M

AU - San José Cáceres, A

AU - Delorme, R

AU - Moscoso, A

AU - Moreno, C

AU - Calvo, R

AU - Canal-Bedia, R

AU - Franco Martín, M A

AU - Charman, T

AU - Strydom, A

AU - Parr, J R

AU - Urbiola Merino, E

AU - Burdeus-Olavarrieta, M

AU - Hernández Jusdado, P

AU - Solis, A

AU - Lucas, M

AU - Sipos, L

AU - González Navarro, P

AU - Blázquez, A

AU - Lázaro, L

AU - Tomás, A

AU - Humeau, E

AU - Antoun, S

AU - Cooke, J

AU - Megalogeni, M

AU - Liang, H

AU - de-Vena-Díez, V B

AU - Leonard, H

AU - White, N

AU - Wang, P

AU - Walton-Bowen, K

AU - Winter-van Rossum, I

AU - Murphy, D

AU - Arango, C

PY - 2026/2

Y1 - 2026/2

N2 - BACKGROUND: Previous 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.METHODS: AIMS-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.FINDINGS: 122 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).INTERPRETATION: Although 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.FUNDING: Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394.

AB - BACKGROUND: Previous 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.METHODS: AIMS-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.FINDINGS: 122 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).INTERPRETATION: Although 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.FUNDING: Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394.

U2 - 10.1016/j.eclinm.2026.103760

DO - 10.1016/j.eclinm.2026.103760

M3 - Article

C2 - 41631164

SN - 2589-5370

VL - 92

JO - EClinicalMedicine

JF - EClinicalMedicine

M1 - 103760

ER -

Efficacy, safety, and tolerability of arbaclofen in Autistic children and adolescents, the AIMS-2-TRIALS-CT1: a randomized, double-blind, placebo-controlled phase II trial

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