Effects of Balovaptan on Health-Related Quality of Life of Adult Males with Autism Spectrum Disorder: Results from a Phase 2 Randomized Double-Blind Placebo-Controlled Study (VANILLA)

Background: Impaired social communication and social interaction are core symptoms of autism spectrum disorder (ASD), causing multiple challenges and affecting quality of life. Alleviating core symptoms may improve quality of life in individuals with ASD.

Objectives: The phase 2 VANILLA study investigated the efficacy and safety of balovaptan, a selective V1a receptor antagonist, in adult men with ASD and intelligence quotient ≥ 70 for the treatment of social and communication deficits. An exploratory objective was to evaluate the effect of 12-week treatment with balovaptan on health-related quality of life (HRQoL).

Methods: VANILLA (NCT01793441) was a 12-week, staggered parallel-group, randomized, double-blind, placebo-controlled study evaluating oral balovaptan 1.5, 4, or 10 mg per day. Participant HRQoL was assessed at baseline, week 6, and week 12 using the PedsQL™ Generic Core Scales v4.0, which has Young Adult (age, 18–25 years) and Adult (age, ≥ 26 years) versions. The scale assesses functioning in 4 domains: physical, emotional, social, and school/work, from which Total, Physical Health Summary (Physical Functioning), and Psychosocial Health Summary (Emotional, Social, and School Functioning) scores are derived. The PedsQL Family Impact Module and Cognitive Functioning Scale were used to assess impact of acute and chronic health conditions on parents and family, and cognitive functioning, respectively. Treatment comparisons of change from baseline at week 12 were estimated using a mixed model repeated measurements analysis of covariance. Since HRQoL was an exploratory endpoint, estimates for the differences between balovaptan doses and placebo with associated 90% confidence intervals (CIs) and P values are provided for descriptive purposes only.

Results: The study enrolled 223 participants, with 56 included in the analysis of balovaptan 10 mg (n = 30) compared with placebo (n = 26) at week 12. Clinically relevant differences were observed for 10 mg balovaptan compared with placebo on the PedsQL Generic Core Scale total score (estimate difference [ED], 7.15; 90% CI, 2.09–12.20; P = 0.021; effect size [ES], 0.63) and on the Psychosocial Health Summary score (ED, 8.53; 90% CI, 2.79–14.27; P = 0.016; ES, 0.67). No significant difference was observed on the Physical Health Summary score (ED, 4.14; 90% CI, −0.19–10.20; P = 0.257; ES, 0.31). Trends for improvement from baseline at week 12 were also observed in the balovaptan 10 mg group compared with placebo on the PedsQL Cognitive Functioning Scale (ED, 9.15; 90% CI, 1.81–16.49; P = 0.042; ES, 0.56). No differences were observed between any dose of balovaptan and placebo at week 12 on the PedsQL Family Impact Module.

Conclusions: The VANILLA trial showed positive trends of improvement in HRQoL with balovaptan 10 mg compared with placebo in adult men with ASD. Trends for improvement in the PedsQL Generic Core Scale and Cognitive Functioning Scale were observed with balovaptan 10 mg compared with placebo, suggesting meaningful improvements in HRQoL. To fully determine the effect of balovaptan on HRQoL, ongoing and future studies will be critical to replicate this signal and to extend these finding across the age and gender spectrum of individuals with ASD.