A Study to Investigate the Efficacy and Safety of Balovaptan (RO5285119) in Participants With Autism Spectrum Disorder (ASD)

Roche

Status and phase: Terminated; Phase 2

Conditions: Autism Spectrum Disorder

Treatments: Drug: Placebo; Drug: RO5285119

Study type: Interventional

Funder types: Industry

Identifiers

NCT02901431

BP30153

Details and patient eligibility

About

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.

Enrollment: 339 patients

Sex: All

Ages: 5 to 17 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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339 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.

Treatment:

Drug: Placebo

Balovaptan (RO5285119) 10 mg/d equivalent

Experimental group

Description:

Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks (up to 52 additional weeks for those enrolled in the OLE).

Treatment:

Drug: RO5285119

Balovaptan (RO5285119) 4 mg/d equivalent

Experimental group

Description:

Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 mg/d of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks. This arm is open only to those participants enrolled prior to Version 6 of the study protocol.

Treatment:

Drug: RO5285119