Balovaptan, an oral selective vasopressin 1a receptor antagonist, did not show efficacy for improving socialization and communication among children with autism spectrum disorder (ASD), according to results of a randomized clinical trial, published in JAMA Psychiatry.
Pediatric patients (N=167) with ASD were recruited at 41 sites in the United States for the aV1ation study between 2016 and 2019. Participants were stratified by age and gender and randomized in a 1:1 ratio to receive age-adjusted equivalent of the adult 10-mg dose of Balovaptan (n=86) or placebo (n=81) for 24 weeks. The primary outcome was change in the Vineland-II 2-domain composite (2DC) score.
The Balovaptan and placebo cohorts were aged median 11.5 (range, 5-17) and 12.0 (range, 5-17) years, 83.7% and 82.7% were boys, 79.1% and 80.2% were White, and 77.9% and 87.7% had a psychiatric comorbidity, respectively.
At week 24, Balovaptan was not favored for improving Vineland-II 2DC (adjusted least-squares mean [aLSM] difference, -0.16; 95% CI, -2.56 to 2.23), Vineland-II Adaptive Behavior Composite (aLSM difference, -0.23; 95% CI, -2.67 to 2.22), Vineland-II Communication (aLSM difference, 0.71; 95% CI, -1.60 to 3.02), Vineland-II Socialization (aLSM difference, -0.61; 95% CI, -3.74 to 2.51), or Vineland-II Daily living skills (aLSM difference, 0.18; 95% CI, -2.87 to 3.22) scores.
At week 12, Balovaptan was favored for improving the Pediatric Quality of Life Inventory (PedsQL) Generic score (aLSM difference, 3.74; 95% CI, 0.78-6.70; P =.04), however, the effect was no longer observed at week 24 (aLSM difference, 2.28; 95% CI, -0.73 to 5.29; P =.21).
A similar proportion of active and control groups reported adverse events (76.7% vs 75.3%). The most common events were nasopharyngitis (24.4% vs 12.3%), headache (16.3% vs 16.0%), diarrhea (12.8% vs 4.9%), and oropharyngeal pain (10.5% vs 7.4%), respectively. One serious event of suicidal ideation was observed in the Balovaptan group, and 4 events of intentional self-injury, aggression, depression, and viral gastroenteritis were observed in the placebo group. A total of 3 Balovaptan recipients withdrew due to anxiety or irritability and 4 placebo recipients withdrew due to irritability, troponin T increase, weight increase, or headache.
The major limitation of this study was that the study population did not reflect the diversity of the United States, instead it was biased toward White, non-Hispanic individuals.
The study authors concluded, “The phase 2 aV1ation randomized controlled trial did not meet its primary efficacy endpoint of improvement in change from baseline in Vineland-II 2DC score with Balovaptan treatment compared with placebo in children and adolescents with ASD and intellectual quotient of 70 [and] Greater at 24 weeks. […] Results suggest that V1a receptor antagonism does not improve social and communication function in pediatric ASD.”
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Hollander E, Jacob S, Jou R, et al. Balovaptan vs placebo for social communication in childhood autism spectrum disorder: A randomized clinical trial. JAMA Psychiatry. Published online July 6, 2022. doi:10.1001/jamapsychiatry.2022.1717