Cargando…

Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder: A Randomized Clinical Trial

IMPORTANCE: There are no approved medications for the core symptoms of autism spectrum disorder (ASD), socialization and communication difficulties. OBJECTIVE: To evaluate the efficacy and safety of balovaptan, an oral selective vasopressin 1a receptor antagonist, compared with placebo in children a...

Descripción completa

Detalles Bibliográficos
Autores principales: Hollander, Eric, Jacob, Suma, Jou, Roger, McNamara, Nora, Sikich, Linmarie, Tobe, Russell, Smith, Janice, Sanders, Kevin, Squassante, Lisa, Murtagh, Lorraine, Gleissl, Teresa, Wandel, Christoph, Veenstra-VanderWeele, Jeremy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260643/
https://www.ncbi.nlm.nih.gov/pubmed/35793101
http://dx.doi.org/10.1001/jamapsychiatry.2022.1717
_version_ 1784742084229464064
author Hollander, Eric
Jacob, Suma
Jou, Roger
McNamara, Nora
Sikich, Linmarie
Tobe, Russell
Smith, Janice
Sanders, Kevin
Squassante, Lisa
Murtagh, Lorraine
Gleissl, Teresa
Wandel, Christoph
Veenstra-VanderWeele, Jeremy
author_facet Hollander, Eric
Jacob, Suma
Jou, Roger
McNamara, Nora
Sikich, Linmarie
Tobe, Russell
Smith, Janice
Sanders, Kevin
Squassante, Lisa
Murtagh, Lorraine
Gleissl, Teresa
Wandel, Christoph
Veenstra-VanderWeele, Jeremy
author_sort Hollander, Eric
collection PubMed
description IMPORTANCE: There are no approved medications for the core symptoms of autism spectrum disorder (ASD), socialization and communication difficulties. OBJECTIVE: To evaluate the efficacy and safety of balovaptan, an oral selective vasopressin 1a receptor antagonist, compared with placebo in children and adolescents with ASD. DESIGN, SETTING, AND PARTICIPANTS: The aV1ation study was a randomized, double-blind, 24-week, parallel-group, placebo-controlled phase 2 trial. Between November 22, 2016, and September 3, 2019, individuals were screened and randomly assigned to treatment groups. The primary efficacy analysis population comprised participants taking age-adjusted balovaptan equivalent to a 10-mg adult dose and participants from the concurrently randomized placebo group. This multicenter trial took place across 41 sites in the US. Participants were aged 5 to 17 years with diagnosed ASD and an IQ of 70 or greater. Data were analyzed from April 8 to November 16, 2020. INTERVENTIONS: Participants were randomly assigned to daily 4-mg or 10-mg adult-equivalent balovaptan or placebo, until the 4-mg group was discontinued. MAIN OUTCOMES AND MEASURES: The primary end point was change from baseline on the Vineland-II two-domain composite (2DC; socialization and communication domains) score at week 24. RESULTS: Between November 2016 and September 2019, a total of 599 individuals were screened and 339 participants were randomly assigned to receive 4-mg balovaptan adult-equivalent dose (91 [26.8%]), 10-mg balovaptan adult-equivalent dose (126 [37.2%]), or placebo (122 [36.0%]). Primary analysis included 86 participants assigned to receive 10-mg balovaptan adult-equivalent dose and 81 assigned to receive placebo (mean [SD] age, 12.1 [3.4] years; 139 male participants [83.2%]). No statistically significant differences were observed between the balovaptan and placebo groups in change from baseline on the Vineland-II 2DC score at week 24 (difference in adjusted least-squares mean, −0.16; 90% CI, −2.56 to 2.23; P = .91). No improvements for balovaptan vs placebo were observed at week 24 for any secondary end points. Balovaptan was well tolerated with no emerging safety concerns. Similar proportions of participants reported adverse events (balovaptan, 66 of 86 [76.7%] vs placebo, 61 of 81 [75.3%]) and serious adverse events (balovaptan, 1 of 86 [1.2%] vs placebo, 4 of 81 [4.9%]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, balovaptan did not demonstrate efficacy in improvement of socialization and communication in this population with pediatric ASD. Balovaptan was well tolerated in children 5 years or older. Further development of robust, sensitive, and objective outcome measures may help to improve future studies in the assessment of therapies targeting communication and socialization in pediatric ASD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02901431
format Online
Article
Text
id pubmed-9260643
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Medical Association
record_format MEDLINE/PubMed
spelling pubmed-92606432022-07-25 Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder: A Randomized Clinical Trial Hollander, Eric Jacob, Suma Jou, Roger McNamara, Nora Sikich, Linmarie Tobe, Russell Smith, Janice Sanders, Kevin Squassante, Lisa Murtagh, Lorraine Gleissl, Teresa Wandel, Christoph Veenstra-VanderWeele, Jeremy JAMA Psychiatry Original Investigation IMPORTANCE: There are no approved medications for the core symptoms of autism spectrum disorder (ASD), socialization and communication difficulties. OBJECTIVE: To evaluate the efficacy and safety of balovaptan, an oral selective vasopressin 1a receptor antagonist, compared with placebo in children and adolescents with ASD. DESIGN, SETTING, AND PARTICIPANTS: The aV1ation study was a randomized, double-blind, 24-week, parallel-group, placebo-controlled phase 2 trial. Between November 22, 2016, and September 3, 2019, individuals were screened and randomly assigned to treatment groups. The primary efficacy analysis population comprised participants taking age-adjusted balovaptan equivalent to a 10-mg adult dose and participants from the concurrently randomized placebo group. This multicenter trial took place across 41 sites in the US. Participants were aged 5 to 17 years with diagnosed ASD and an IQ of 70 or greater. Data were analyzed from April 8 to November 16, 2020. INTERVENTIONS: Participants were randomly assigned to daily 4-mg or 10-mg adult-equivalent balovaptan or placebo, until the 4-mg group was discontinued. MAIN OUTCOMES AND MEASURES: The primary end point was change from baseline on the Vineland-II two-domain composite (2DC; socialization and communication domains) score at week 24. RESULTS: Between November 2016 and September 2019, a total of 599 individuals were screened and 339 participants were randomly assigned to receive 4-mg balovaptan adult-equivalent dose (91 [26.8%]), 10-mg balovaptan adult-equivalent dose (126 [37.2%]), or placebo (122 [36.0%]). Primary analysis included 86 participants assigned to receive 10-mg balovaptan adult-equivalent dose and 81 assigned to receive placebo (mean [SD] age, 12.1 [3.4] years; 139 male participants [83.2%]). No statistically significant differences were observed between the balovaptan and placebo groups in change from baseline on the Vineland-II 2DC score at week 24 (difference in adjusted least-squares mean, −0.16; 90% CI, −2.56 to 2.23; P = .91). No improvements for balovaptan vs placebo were observed at week 24 for any secondary end points. Balovaptan was well tolerated with no emerging safety concerns. Similar proportions of participants reported adverse events (balovaptan, 66 of 86 [76.7%] vs placebo, 61 of 81 [75.3%]) and serious adverse events (balovaptan, 1 of 86 [1.2%] vs placebo, 4 of 81 [4.9%]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, balovaptan did not demonstrate efficacy in improvement of socialization and communication in this population with pediatric ASD. Balovaptan was well tolerated in children 5 years or older. Further development of robust, sensitive, and objective outcome measures may help to improve future studies in the assessment of therapies targeting communication and socialization in pediatric ASD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02901431 American Medical Association 2022-07-06 2022-08 /pmc/articles/PMC9260643/ /pubmed/35793101 http://dx.doi.org/10.1001/jamapsychiatry.2022.1717 Text en Copyright 2022 Hollander E et al. JAMA Psychiatry. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the CC-BY-NC-ND License.
spellingShingle Original Investigation
Hollander, Eric
Jacob, Suma
Jou, Roger
McNamara, Nora
Sikich, Linmarie
Tobe, Russell
Smith, Janice
Sanders, Kevin
Squassante, Lisa
Murtagh, Lorraine
Gleissl, Teresa
Wandel, Christoph
Veenstra-VanderWeele, Jeremy
Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder: A Randomized Clinical Trial
title Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder: A Randomized Clinical Trial
title_full Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder: A Randomized Clinical Trial
title_fullStr Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder: A Randomized Clinical Trial
title_full_unstemmed Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder: A Randomized Clinical Trial
title_short Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder: A Randomized Clinical Trial
title_sort balovaptan vs placebo for social communication in childhood autism spectrum disorder: a randomized clinical trial
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260643/
https://www.ncbi.nlm.nih.gov/pubmed/35793101
http://dx.doi.org/10.1001/jamapsychiatry.2022.1717
work_keys_str_mv AT hollandereric balovaptanvsplaceboforsocialcommunicationinchildhoodautismspectrumdisorderarandomizedclinicaltrial
AT jacobsuma balovaptanvsplaceboforsocialcommunicationinchildhoodautismspectrumdisorderarandomizedclinicaltrial
AT jouroger balovaptanvsplaceboforsocialcommunicationinchildhoodautismspectrumdisorderarandomizedclinicaltrial
AT mcnamaranora balovaptanvsplaceboforsocialcommunicationinchildhoodautismspectrumdisorderarandomizedclinicaltrial
AT sikichlinmarie balovaptanvsplaceboforsocialcommunicationinchildhoodautismspectrumdisorderarandomizedclinicaltrial
AT toberussell balovaptanvsplaceboforsocialcommunicationinchildhoodautismspectrumdisorderarandomizedclinicaltrial
AT smithjanice balovaptanvsplaceboforsocialcommunicationinchildhoodautismspectrumdisorderarandomizedclinicaltrial
AT sanderskevin balovaptanvsplaceboforsocialcommunicationinchildhoodautismspectrumdisorderarandomizedclinicaltrial
AT squassantelisa balovaptanvsplaceboforsocialcommunicationinchildhoodautismspectrumdisorderarandomizedclinicaltrial
AT murtaghlorraine balovaptanvsplaceboforsocialcommunicationinchildhoodautismspectrumdisorderarandomizedclinicaltrial
AT gleisslteresa balovaptanvsplaceboforsocialcommunicationinchildhoodautismspectrumdisorderarandomizedclinicaltrial
AT wandelchristoph balovaptanvsplaceboforsocialcommunicationinchildhoodautismspectrumdisorderarandomizedclinicaltrial
AT veenstravanderweelejeremy balovaptanvsplaceboforsocialcommunicationinchildhoodautismspectrumdisorderarandomizedclinicaltrial