A Study to Investigate the Efficacy and Safety of Balovaptan (RO5285119) in Participants With Autism Spectrum Disorder (ASD)
Condition: Autism Spectrum Disorder
MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Intervention: Placebo; RO5285119
Intervention description: Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.; Participants received age-adjusted total daily oral dose approximately equivalent to the adult doses of either 4 mg/d or 10 mg/d of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks (up to 52 additional weeks for those enrolled in the OLE).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 339.0
Sex: All
Minimum age: 5 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      For participants enrolled prior to Version 6 of the protocol: This was a Phase II
      multi-center, randomized, double-blind, 24-week, 3-arm, parallel group, placebo-controlled
      study to investigate the efficacy, safety, and pharmacokinetics of balovaptan in children and
      adolescents aged 5-17 years with ASD who are high functioning (intelligence quotient [IQ]
      greater than or equal to [>=] 70).

      For participants enrolled according to Version 6 of the protocol: This was a Phase II
      multi-center, randomized, double-blind, 24-week, parallel group, placebo-controlled, 2-arm
      study with participants assigned either to a 10 milligram (mg) or equivalent dose of
      balovaptan, or placebo. All other study parameters remained as stated above.

      There are three parts to this study: PK Part (Study part 1) included up to 8 weeks of
      treatment, Main Treatment Part (Study part 2) included 24 week of treatment, and the Open
      Label Extension Part (Study part 3) included Week 24 to Week 76 of treatment.

      All participants that completed the 24-week treatment period were eligible to participate in
      an optional 52-week open-label extension (OLE) during which they received balovaptan
      treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Fluent in English

          -  Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria
             for ASD or International Statistical Classification of Diseases and Related Health
             Problems, 10th revision (ICD10) criteria for Autism diagnosis confirmed by Autism
             Diagnostic Observational Schedule (ADOS-2) criteria

          -  Social Responsiveness Scale, second edition (SRS-2) (T-score) >= 66

          -  Clinical Global Impressions of Severity (CGI-S) >= 4 (moderately ill) at screening

          -  IQ >= 70 as assessed by Wechsler Abbreviated Scale of Intelligence Scale: Second
             Edition (WASI-II) or Wechsler Preschool and Primary Scale of Intelligence: Fourth
             Edition (WPPSI-IV) intelligence test

          -  Language, hearing, and vision compatible with the study measurements as judged by the
             investigator

        Inclusion Criteria for the OLE:

          -  Have completed the blinded treatment phase of the study OR were required to stop
             dosing at or before Week 8

          -  Have no adverse events that would prohibit starting the OLE

        Exclusion Criteria:

          -  Initiation of a major change in psychosocial intervention (including investigational)
             within 4 weeks prior to screening

          -  Unstable or uncontrolled clinically significant psychiatric and/or neurological
             disorder that may interfere with the safety or efficacy endpoints

          -  Known personal or family history of cerebral aneurysm

          -  Risk of suicidal behavior

          -  Seizure within the past 6 months

          -  Medical history of alcohol or substance abuse/dependence

          -  Concurrent cardio-vascular disease not considered well controlled by the Investigator

          -  Clinically significant abnormality on electrocardiogram at screening

          -  Concomitant disease or condition (pulmonary, gastro-intestinal, hepatic, renal,
             metabolic, immunological system, or obesity that could interfere with the conduct of
             the study

          -  Evidence for current gastro-intestinal bleeding, e.g., active stomach ulcer disease

          -  History of coagulopathies, bleeding disorders, or blood dyscrasias

          -  Positive serology for hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency
             virus (HIV) 1, or HIV 2

          -  Confirmed clinically significant abnormality in parameters of hematology, clinical
             chemistry, coagulation, or urinalysis

          -  Medical history of malignancy if not considered cured

          -  Participation in an investigational drug study within 90 days or 5 times the half-life
             of the investigational molecule (whichever is longer) prior to randomization

          -  Loss of blood over 250 milliliters within three months prior to screening

          -  Allowed medications have not been stable since 4 weeks before screening, and allowed
             medications for treatment of epilepsy have not been stable since 3 months before
             screening

          -  Use of prohibited medications within 2 weeks prior to screening visit or 5 times the
             half-life prior to randomization (whichever is longer)