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

NCT02901431 | Terminated Phase 2 Results

• 1 other identifier: BP30153
• Study Type: interventional
• Target: 339
• Locations: 1 country
• Sites: 45

Brief 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.

Conditions

Autism Spectrum Disorder

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Vineland™-II Adaptive Behavior Scale Two Domain Composite (2DC) Score at Week 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

  Vineland™-II Adaptive Behavior Scales 2-Domain Composite (2DC) Score is defined as mean of the Communication domain standard score \& Socialization domain standard score. If any of the 2 individual domain standard scores is missing 2DC score is not computed. Vineland™-II is an instrument that measures communication, daily living skills, socialization, motor skills and maladaptive behavior of individuals with developmental disabilities. Survey Interview Form will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning. Mixed model with repeated measures (MMRM) was used for analysis with assessments at baseline, week 12 and week 24.

  Baseline, Week 24

Secondary Outcomes (11)

• Change From Baseline in Vineland™-II Composite Standard Score After 12 Weeks and 24 Weeks of Treatment for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

  Baseline, Weeks 12 and 24

• Change From Baseline in Vineland™-II Adaptive Behavior Scale Communication, Socialization, and Daily Living Skills Domain Standard Scores at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

  Baseline, Weeks 12 and 24

• Proportion of Subjects With >=6 Points Improvement in the Vineland-II 2DC Score for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

  Baseline, Weeks 12 and 24

• Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

  Baseline, Weeks 12 and 24

• Change From Baseline in Ohio Autism Clinical Impressions Scale-Severity (OACIS-S) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

  Baseline, Weeks 12 and 24

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Balovaptan (RO5285119) 10 mg/d equivalent

EXPERIMENTAL

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).

Drug: RO5285119

Balovaptan (RO5285119) 4 mg/d equivalent

EXPERIMENTAL

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.

Drug: RO5285119

Interventions

Placebo DRUG

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

Placebo

RO5285119 DRUG

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).

Balovaptan (RO5285119) 10 mg/d equivalent; Balovaptan (RO5285119) 4 mg/d equivalent

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (45)

Harmonex Neuroscience Research

Dothan, Alabama, 36303, United States

Location

Southwest Autism Research & Resource Center

Phoenix, Arizona, 85006, United States

Location

NRC Research Institute

Orange, California, 92868, United States

Location

PCSD Feighner Research

San Diego, California, 92108, United States

Location

University of California at San Francisco

San Francisco, California, 94115, United States

Location

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

DBA IMMUNOe Int'l Res Center

Centennial, Colorado, 80112, United States

Location

Yale University / Yale-New Haven Hospital

New Haven, Connecticut, 06519-1124, United States

Location

Sarkis Clinical Trials

Gainesville, Florida, 32607, United States

Location

Segal trials

North Miami, Florida, 33161, United States

Location

Medical Research Group of Central Florida

Orange City, Florida, 32763, United States

Location

APG- Advanced Psychiatric Group

Orlando, Florida, 32803, United States

Location

USF Rothman Center

St. Petersburg, Florida, 33701, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Capstone Clinical Research

Libertyville, Illinois, 60048, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Childrens Hospital

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital; Lurie Center for Autism

Lexington, Massachusetts, 02421, United States

Location

UMASS Medical School

Worcester, Massachusetts, 01655, United States

Location

University of Minnesota; Clin. Neuro Research Unit

Minneapolis, Minnesota, 55414, United States

Location

St. Charles Psychiatric Associates

Saint Charles, Missouri, 63304, United States

Location

Midwest Childrens Health Research Institute

Lincoln, Nebraska, 68516, United States

Location

Center for Autism and the Developing Brain

New York, New York, 10032, United States

Location

Nathan S. Kline Institute for Psychiatric Research

Orangeburg, New York, 10962, United States

Location

University of Rochester

Rochester, New York, 14627 0001, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

DUKE SCHOOL OF MEDICINE;Duke Center for Autism and Brain Development

Durham, North Carolina, 27705, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University Hospitals

Cleveland, Ohio, 44106, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Cutting Edge Research Group

Oklahoma City, Oklahoma, 73116, United States

Location

Suburban Research Associates

Media, Pennsylvania, 19063, United States

Location

Children's Hospital of Philadelphia;Allergy/Immunology Department

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Western Psychiatric Institute and Clinic

Pittsburgh, Pennsylvania, 15203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

BioBehavioral Research of Austin, PC

Austin, Texas, 78759, United States

Location

Relaro Medical Trials

Dallas, Texas, 75243, United States

Location

Red Oak Psychiatry Associates, PA

Houston, Texas, 77090, United States

Location

Road Runner Research

San Antonio, Texas, 78249, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98007, United States

Location

Pacific Institute of Medical Sciences

Bothell, Washington, 98011, United States

Location

Core Clinical Research

Everett, Washington, 98201, United States

Location

Seattle Children's Research Institute; Psychiatry and Behavioral Medicine

Seattle, Washington, 98121, United States

Location

Related Publications (1)

• Hollander E, Jacob S, Jou R, McNamara N, Sikich L, Tobe R, Smith J, Sanders K, Squassante L, Murtagh L, Gleissl T, Wandel C, Veenstra-VanderWeele J. Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Aug 1;79(8):760-769. doi: 10.1001/jamapsychiatry.2022.1717.

  PMID: 35793101 DERIVED

MeSH Terms

Conditions

Autism Spectrum Disorder

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Limitations and Caveats

Study was terminated early, therefore, there was limited data collected in Open Label Extension part of the study.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2016
• First Posted: September 15, 2016
• Study Start: November 21, 2016
• Primary Completion: April 15, 2020
• Study Completion: June 30, 2020
• Last Updated: February 8, 2021
• Results First Posted: February 8, 2021

Record last verified: 2021-01

Locations

US (45)