Clinical trial NCT03504917: A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Efficacy, and Safety Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Autism Spectrum Disorder
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-04-20
Enrollment: 322
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy, safety, and pharmacokinetics of 10 mg of oral administration balovaptan once a day (QD) compared with matching placebo in adults (18 years and older) with autism spectrum disorder (ASD).


Eligibility criteria: Inclusion Criteria:

* Subject meets the DSM-5 criteria for ASD for an autism diagnosis and is confirmed using ADOS-2 criteria
* SRS-2, proxy version, total t-score \>=66 at screening
* A full scale IQ score \>=70 on the WASI®-II
* Subject has an appropriate study partner, in the opinion of the investigator
* For women of childbearing potential: agreement to remain abstinent or use a contraceptive method with a failure rate of \<1% per year during the treatment period and for at least 28 days after the last dose of study drug
* Treatment with permitted medications (at a stable dose for 12 weeks before screening) and behavioral therapy regimens (regimens stable for 6 weeks before screening), with the intent that such treatments remain stable throughout the study and with no expected changes before the Week 24 visit

Exclusion Criteria:

* Pregnancy or breastfeeding, or intention to become pregnant during the study
* Previous initiation of new or major change in psychosocial intervention within 6 weeks prior to screening
* Unstable or uncontrolled clinically significant affective or psychotic disorders and/or neurologic disorder that may interfere with the assessment of safety or efficacy endpoints
* Substance use disorders during the last 12 months
* Significant risk for suicidal behavior, in the opinion of the investigator
* Epilepsy or seizure disorder considered not well controlled within the past 6 months or changes in anticonvulsive therapy within the last 6 months
* Clinical diagnosis of peripheral neuropathy
* Within the last 2 years, unstable or clinically significant cardiovascular disease
* Uncontrolled hypertension
* Unexplained syncopal episode within the last 12 months
* Confirmed elevation above upper limit of normal of CK-MB, high sensitivity cardiac troponin T, cardiac troponin I, and/or N-terminal pro B-type natriuretic peptide
* Positive serology results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) 1 or 2
* History of coagulopathies, bleeding disorders, blood dyscrasias, hematological malignancies, myelosuppression (including iatrogenic), or current major bleeding event
* Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or what would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
* Confirmed clinically significant abnormality in parameters of hematology
* Confirmed clinically significant abnormality in parameters of clinical chemistry, coagulation, or urinalysis
* Medical history of malignancy, if not considered cured

Primary outcomes:
measure: Change From Baseline at Week 24 on the Vineland Adaptive Behavior Scales (Vineland-II) Two-domain Composite (2DC) Score.
timeFrame: Week 24
Secondary outcomes:
measure: Change From Baseline at Week 12 on the Vineland-II 2DC Score
timeFrame: Week 12
measure: Change From Baseline at Weeks 12 and 24 in the Pediatric Quality of Life (PedsQL) Inventory Generic Core Scales, Version 4.0, on Summary and Total Scores
timeFrame: Weeks 12 and 24
measure: Change From Baseline at Weeks 12 and 24 in the Vineland-II Adaptive Behavior Composite Standard Score
timeFrame: Weeks 12 and 24
measure: Change From Baseline at Week 12 and 24 on the Vineland-II Socialization Domain Standard Score
timeFrame: Baseline, Weeks 12 and 24
measure: Change From Baseline at Weeks 12 and 24 on the Vineland-II Communication Domain Standard Score
timeFrame: Weeks 12 and 24
measure: Change From Baseline at Weeks 12 and 24 on the Vineland-II Daily Living Skills Domain Standard Score
timeFrame: Weeks 12 and 24
measure: Change From Baseline in Severity of Clinical Impressions as Measured by Clinical Global Impression-Severity (CGI-S)
timeFrame: Weeks 12 and 24
measure: Improvements in Clinical Impressions, as Measured by Clinical Global Impression-Improvement (CGI-I)
timeFrame: Weeks 12 and 24
measure: Change From Baseline at Weeks 12 and 24 in the Hamilton Anxiety Rating Scale (HAM-A) Total and Domain Scores
timeFrame: Weeks 12 and 24
measure: Proportion of Subjects With a >=6-point Improvement in Vineland-II 2DC Score
timeFrame: Weeks 12 and 24
measure: Percentage of Participants With Adverse Events
timeFrame: Week 24 and Up to Approximately 2 Years
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: Rogers
country: United States
facility: Woodland Research Northwest, LLC
state: Arkansas
city: Los Angeles
country: United States
facility: University of California , Los Angeles (UCLA); Child, Adolescent Psychiatry
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: Colorado Springs
country: United States
facility: MCB Clinical Research Centers
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: Orlando
country: United States
facility: APG- Advanced Psychiatric Group
state: Florida
city: Palmetto Bay
country: United States
facility: IMIC Inc.
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: Uni of Chicago; Centre For Advanced Medicine
state: Illinois
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials, LLC
state: Louisiana
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center-Fairview
state: Minnesota
city: Saint Louis
country: United States
facility: Millennium Psychiatric Associates, LLC
state: Missouri
city: New York
country: United States
facility: Hapworth Research Inc.
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: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
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: Pittsburgh
country: United States
facility: UPMC Western Psychiatric Institute and Clinic
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center; Department of Psychiatry
state: Tennessee
city: Austin
country: United States
facility: BioBehavioral Research of Austin, PC
state: Texas
city: Houston
country: United States
facility: Red Oak Psychiatry Associates, PA
state: Texas
city: Orem
country: United States
facility: Aspen Clinical Research
state: Utah
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Kelowna
country: Canada
facility: Okanagan Clinical Trials
state: British Columbia
city: East York
country: Canada
facility: Holland Bloorview Kids Rehabilitation Hospital; Autism Research Centre
state: Ontario
city: London
country: Canada
facility: University of Western Ontario
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre - Glen Site
state: Quebec
city: Bordeaux
country: France
facility: Hopital Charles Perrens; Centre de Ressources Autisme Aquitaine
city: LYON Cedex
country: France
facility: Hospices Civils de Lyon; Centre d'Investigation Clinique Pédiatrique
city: Sotteville Les Rouen
country: France
facility: Centre hospitalier du Rouvray; CRAHN Centre de Ressources Autisme Haute-Normandie
city: Pavia
country: Italy
facility: ASST di Pavia; Dip. di Scienze del Sistema Nervoso e del Comportamento
state: Lombardia
city: Piacenza
country: Italy
facility: AUSL di Piacenza; Psichiatria di Collegamento
state: Lombardia
city: Torino
country: Italy
facility: ASL TO2; Centro Pilota Regione Piemonte - Dip. Salute Mentale
state: Piemonte
city: Catania
country: Italy
facility: A.O.U. Policlinico - V. Emanuele - P.O. Gaspare Rodolico; Dip. Terapia integrata disturbi resistenti
state: Sicilia
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa; Departamento de Psiquiatria
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron; Sevicio de Psiquiatría
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon; Servicio de Psiquiatria del niño y del adolescente
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega; Departamento de Psiquiatria
city: Edinburgh
country: United Kingdom
facility: Western General Hospital; Wellcome Trust CRF
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital; Clinical Research Facility
city: London
country: United Kingdom
facility: Kings College Hospital; Kings Clinical Research Facility
city: London
country: United Kingdom
facility: RE:Cognition Health; RE:Cognition Health
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Jacob S, Veenstra-VanderWeele J, Murphy D, McCracken J, Smith J, Sanders K, Meyenberg C, Wiese T, Deol-Bhullar G, Wandel C, Ashford E, Anagnostou E. Efficacy and safety of balovaptan for socialisation and communication difficulties in autistic adults in North America and Europe: a phase 3, randomised, placebo-controlled trial. Lancet Psychiatry. 2022 Mar;9(3):199-210. doi: 10.1016/S2215-0366(21)00429-6. Epub 2022 Feb 10.