Clinical trial NCT02901431: A Study to Investigate the Efficacy and Safety of Balovaptan (RO5285119) in Participants With Autism Spectrum Disorder (ASD)
Official title: A Phase II Multi-Center, Randomized, Double-Blind, 24-Week, Parallel Group, Placebo-Controlled Study to Investigate the Efficacy and Safety of Balovaptan (RO5285119) in Children and Adolescents Age 5-17 With Autism Spectrum Disorder (ASD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Autism Spectrum Disorder
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-09-15
Enrollment: 339
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: 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
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: 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
timeFrame: Baseline, Weeks 12 and 24
measure: 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
timeFrame: Baseline, Weeks 12 and 24
measure: Proportion of Subjects With >=6 Points Improvement in the Vineland-II 2DC Score for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
timeFrame: Baseline, Weeks 12 and 24
measure: 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
timeFrame: Baseline, Weeks 12 and 24
measure: 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
timeFrame: Baseline, Weeks 12 and 24
measure: Clinical Global Impressions- Improvement (CGI-I) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
timeFrame: Weeks 12 and 24
measure: Ohio Autism Clinical Impressions Scale- Improvement (OACIS-I) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
timeFrame: Weeks 12 and 24
measure: Change From Baseline in Patient-Reported Pediatric Quality of Life (PedsQL) v4.0 Generic Core Scale After 12 Weeks and 24 Weeks of Treatment for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in Vineland-II Composite Standard Score in Adolescents and Children Independently at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline in Vineland-II Adaptive Behavior Scale 2DC Score at Week 12 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
timeFrame: Baseline, Week 12
measure: Percentage of Participants With Adverse Events for Treatment With Balovaptan
timeFrame: Baseline to Week 24 and up to Week 76
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Harmonex Neuroscience Research
state: Alabama
city: Phoenix
country: United States
facility: Southwest Autism Research & Resource Center
state: Arizona
city: Orange
country: United States
facility: NRC Research Institute
state: California
city: San Diego
country: United States
facility: PCSD Feighner Research
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Centennial
country: United States
facility: DBA IMMUNOe Int'l Res Center
state: Colorado
city: New Haven
country: United States
facility: Yale University / Yale-New Haven Hospital
state: Connecticut
city: Gainesville
country: United States
facility: Sarkis Clinical Trials
state: Florida
city: North Miami
country: United States
facility: Segal trials
state: Florida
city: Orange City
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Orlando
country: United States
facility: APG- Advanced Psychiatric Group
state: Florida
city: Saint Petersburg
country: United States
facility: USF Rothman Center
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Libertyville
country: United States
facility: Capstone Clinical Research
state: Illinois
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Childrens Hospital
state: Massachusetts
city: Lexington
country: United States
facility: Massachusetts General Hospital; Lurie Center for Autism
state: Massachusetts
city: Worcester
country: United States
facility: UMASS Medical School
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota; Clin. Neuro Research Unit
state: Minnesota
city: Saint Charles
country: United States
facility: St. Charles Psychiatric Associates
state: Missouri
city: Lincoln
country: United States
facility: Midwest Childrens Health Research Institute
state: Nebraska
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
city: New York
country: United States
facility: Center for Autism and the Developing Brain
state: New York
city: Orangeburg
country: United States
facility: Nathan S. Kline Institute for Psychiatric Research
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Durham
country: United States
facility: DUKE SCHOOL OF MEDICINE;Duke Center for Autism and Brain Development
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Cutting Edge Research Group
state: Oklahoma
city: Media
country: United States
facility: Suburban Research Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia;Allergy/Immunology Department
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Western Psychiatric Institute and Clinic
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: BioBehavioral Research of Austin, PC
state: Texas
city: Dallas
country: United States
facility: Relaro Medical Trials
state: Texas
city: Houston
country: United States
facility: Red Oak Psychiatry Associates, PA
state: Texas
city: San Antonio
country: United States
facility: Road Runner Research
state: Texas
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Bothell
country: United States
facility: Pacific Institute of Medical Sciences
state: Washington
city: Everett
country: United States
facility: Core Clinical Research
state: Washington
city: Seattle
country: United States
facility: Seattle Children's Research Institute; Psychiatry and Behavioral Medicine
state: Washington
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.