TY - JOUR
T1 - Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder
T2 - A Randomized Clinical Trial
AU - Hollander, Eric
AU - Jacob, Suma
AU - Jou, Roger
AU - McNamara, Nora
AU - Sikich, Linmarie
AU - Tobe, Russell
AU - Smith, Janice
AU - Sanders, Kevin
AU - Squassante, Lisa
AU - Murtagh, Lorraine
AU - Gleissl, Teresa
AU - Wandel, Christoph
AU - Veenstra-Vanderweele, Jeremy
N1 - Publisher Copyright:
© 2022 American Medical Association. All rights reserved.
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
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U2 - 10.1001/jamapsychiatry.2022.1717
DO - 10.1001/jamapsychiatry.2022.1717
M3 - Article
C2 - 35793101
AN - SCOPUS:85134614308
SN - 2168-622X
VL - 79
SP - 760
EP - 769
JO - JAMA Psychiatry
JF - JAMA Psychiatry
IS - 8
ER -