Large multicenter randomized trials in autism: key insights gained from the balovaptan clinical development program

Suma Jacob*, Evdokia Anagnostou, Eric Hollander, Roger Jou, Nora McNamara, Linmarie Sikich, Russell Tobe, Declan Murphy, James McCracken, Elizabeth Ashford, Christopher Chatham, Susanne Clinch, Janice Smith, Kevin Sanders, Lorraine Murtagh, Jana Noeldeke, Jeremy Veenstra-VanderWeele

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Background: Autism spectrum disorder (ASD) is a common and heterogeneous neurodevelopmental condition that is characterized by the core symptoms of social communication difficulties and restricted and repetitive behaviors. At present, there is an unmet medical need for therapies to ameliorate these core symptoms in order to improve quality of life of autistic individuals. However, several challenges are currently faced by the ASD community relating to the development of pharmacotherapies, namely in the conduct of clinical trials. Balovaptan is a V1a receptor antagonist that has been investigated to improve social communication difficulties in individuals with ASD. In this viewpoint, we draw upon our recent first-hand experiences of the balovaptan clinical development program to describe current challenges of ASD trials. Discussion points: The balovaptan trials were conducted in a wide age range of individuals with ASD with the added complexities associated with international trials. When summarizing all three randomized trials of balovaptan, a placebo response was observed across several outcome measures. Placebo response was predicted by greater baseline symptom severity, online recruitment of participants, and less experienced or non-academic trial sites. We also highlight challenges relating to selection of outcome measures in ASD, the impact of baseline characteristics, and the role of expectation bias in influencing trial results. Conclusion: Taken together, the balovaptan clinical development program has advanced our understanding of the key challenges facing ASD treatment research. The insights gained can be used to inform and improve the design of future clinical trials with the collective aim of developing efficacious therapies to support individuals with ASD.

Original languageEnglish
Article number25
JournalMolecular Autism
Issue number1
Publication statusPublished - Dec 2022


  • Autism spectrum disorder
  • aV1ation
  • Balovaptan
  • Placebo response
  • V1aduct


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