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) aged 5 to 17 with ASD were recruited at 41 sites in the United States for the aV1ation study (ClinicalTrials.gov Identifier: NCT02901431) between 2016 and 2019. Participants were stratified by age and gender and randomly assigned in a 1:1 ratio to receive age-adjusted balovaptan equivalent of the adult 10-mg dose (n=86) or placebo (n=81) for 24 weeks. The primary outcome was change in the Vineland-II 2-domain composite (2DC) score from baseline to week 24.
At baseline, patients in the balovaptan and placebo cohorts were similar in age (median, 11.5 years vs 12.0 years), predominantly White (83.7% vs 82.7%, respectively), and had a high likelihood of a psychiatric comorbidity (77.9% vs 87.7%, respectively).
At week 24, balovaptan was not favored for improving Vineland-II 2DC (adjusted least-squares mean [aLSM] difference, -0.16; 90% CI, -2.56 to 2.23; P =.91), Vineland-II Adaptive Behavior Composite (aLSM difference, -0.23; 90% CI, -2.67 to 2.22; P =.88), Vineland-II Communication (aLSM difference, 0.71; 90% CI, -1.60 to 3.02; P =.61), Vineland-II Socialization (aLSM difference, -0.61; 90% CI, -3.74 to 2.51; P =.75), or Vineland-II Daily Living Skills (aLSM difference, 0.18; 90% CI, -2.87 to 3.22; P =.92) scores.
At week 12, balovaptan was favored for improving the Pediatric Quality of Life Inventory (PedsQL) generic score (aLSM difference, 3.74; 90% CI, 0.78-6.70; P =.04), however, the effect was no longer observed at week 24 (aLSM difference, 2.28; 90% CI, -0.73 to 5.29; P =.21).
A similar proportion of participants in the balovaptan and control groups reported adverse events (76.7% vs 75.3%, respectively). 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 patients who received balovaptan withdrew from the study due to anxiety or irritability, and 4 patients who received placebo 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: This study was supported by F. Hoffmann-La Roche Ltd. Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Editor’s Note: The original version of this article included an error in the confidence interval numerals in the fourth paragraph. The correct number for all confidence intervals in this article is 90%. The article was corrected on September 27, 2022, to reflect this.
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