A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension

Autism Spectrum Disorder Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03504917
• Other study ID #: WN39434
• Status: Terminated
• Phase: Phase 3
• Start date: August 8, 2018
• Est. completion date: July 1, 2020

Study information

• Verified date: October 2021
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 322
• Est. completion date: July 1, 2020
• Est. primary completion date: March 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive

Intervention

Drug:
• Balovaptan
Participants will receive 10 mg of oral administration balovaptan once a day (QD).
• Placebo
Participants will receive matching placebo.

Locations

Country	Name	City	State
Canada	Holland Bloorview Kids Rehabilitation Hospital; Autism Research Centre	East York	Ontario
Canada	Okanagan Clinical Trials	Kelowna	British Columbia
Canada	University of Western Ontario	London	Ontario
Canada	McGill University Health Centre - Glen Site	Montreal	Quebec
France	Hopital Charles Perrens; Centre de Ressources Autisme Aquitaine	Bordeaux
France	Hospices Civils de Lyon; Centre d'Investigation Clinique Pédiatrique	LYON Cedex
France	Centre hospitalier du Rouvray; CRAHN Centre de Ressources Autisme Haute-Normandie	Sotteville Les Rouen
Italy	A.O.U. Policlinico - V. Emanuele - P.O. Gaspare Rodolico; Dip. Terapia integrata disturbi resistenti	Catania	Sicilia
Italy	ASST di Pavia; Dip. di Scienze del Sistema Nervoso e del Comportamento	Pavia	Lombardia
Italy	AUSL di Piacenza; Psichiatria di Collegamento	Piacenza	Lombardia
Italy	ASL TO2; Centro Pilota Regione Piemonte - Dip. Salute Mentale	Torino	Piemonte
Spain	Hospital Universitari Vall d'Hebron; Sevicio de Psiquiatría	Barcelona
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Psiquiatria del niño y del adolescente	Madrid
Spain	Hospital Mutua de Terrassa; Departamento de Psiquiatria	Terrassa	Barcelona
Spain	Hospital Universitario Rio Hortega; Departamento de Psiquiatria	Valladolid
United Kingdom	Western General Hospital; Wellcome Trust CRF	Edinburgh
United Kingdom	Queen Elizabeth University Hospital; Clinical Research Facility	Glasgow
United Kingdom	Kings College Hospital; Kings Clinical Research Facility	London
United Kingdom	RE:Cognition Health; RE:Cognition Health	London
United States	BioBehavioral Research of Austin, PC	Austin	Texas
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Northwest Clinical Research Center	Bellevue	Washington
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	Uni of Chicago; Centre For Advanced Medicine	Chicago	Illinois
United States	University Hospitals	Cleveland	Ohio
United States	MCB Clinical Research Centers	Colorado Springs	Colorado
United States	Ohio State University	Columbus	Ohio
United States	Harmonex Neuroscience Research	Dothan	Alabama
United States	Sarkis Clinical Trials	Gainesville	Florida
United States	Red Oak Psychiatry Associates, PA	Houston	Texas
United States	Lake Charles Clinical Trials, LLC	Lake Charles	Louisiana
United States	University of California , Los Angeles (UCLA); Child, Adolescent Psychiatry	Los Angeles	California
United States	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center; Department of Psychiatry	Nashville	Tennessee
United States	Yale University / Yale-New Haven Hospital	New Haven	Connecticut
United States	Center for Autism and the Developing Brain	New York	New York
United States	Hapworth Research Inc.	New York	New York
United States	Cutting Edge Research Group	Oklahoma City	Oklahoma
United States	Nathan S. Kline Institute for Psychiatric Research	Orangeburg	New York
United States	Aspen Clinical Research	Orem	Utah
United States	APG- Advanced Psychiatric Group	Orlando	Florida
United States	IMIC Inc.	Palmetto Bay	Florida
United States	Southwest Autism Research & Resource Center	Phoenix	Arizona
United States	UPMC Western Psychiatric Institute and Clinic	Pittsburgh	Pennsylvania
United States	Woodland Research Northwest, LLC	Rogers	Arkansas
United States	Millennium Psychiatric Associates, LLC	Saint Louis	Missouri
United States	PCSD Feighner Research	San Diego	California
United States	University of California at San Francisco	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Richmond Behavioral Associates	Staten Island	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline at Week 24 on the Vineland Adaptive Behavior Scales (Vineland-II) Two-domain Composite (2DC) Score.	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 study partner in this study, during which the rater or clinician will ask to the study partner 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.	Week 24
Secondary	Change From Baseline at Week 12 on the Vineland-II 2DC Score	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 study partner in this study, during which the rater or clinician will ask to the study partner 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.	Week 12
Secondary	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	The Pediatric Quality of Life Inventory PedsQL™4.0 Generic Core Scale assessment consists of a 23 item questionnaire encompassing 4 core scale domains: Physical Functioning (8 items); Emotional Functioning (5 items); Social Functioning (5 items); and School Functioning (5 items). Items are scored on a 5 point Likert-type response scale (0=never a problem; 1=almost never a problem; 2=sometimes a problem; 3=often a problem; and 4=almost always a problem). Once scored, items will be reverse scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better health-related quality of life.	Weeks 12 and 24
Secondary	Change From Baseline at Weeks 12 and 24 in the Vineland-II Adaptive Behavior Composite Standard Score	The Vineland-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable study partner in this study, during which the rater or clinician will ask to the study partner open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills (up to 6 years only) and used to calculate the Vineland-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning. Only descriptive statistics presented instead of the planned estimated due to the early discontinuation of the study due to futility.	Weeks 12 and 24
Secondary	Change From Baseline at Week 12 and 24 on the Vineland-II Socialization Domain Standard Score	The Vineland-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable study partner in this study, during which the rater or clinician will ask to the study partner open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills (up to 6 years only) and used to calculate the Vineland-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning.; Only descriptive statistics presented instead of the planned estimand due to the early discontinuation of the study due to futility.	Baseline, Weeks 12 and 24
Secondary	Change From Baseline at Weeks 12 and 24 on the Vineland-II Communication Domain Standard Score	The Vineland-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable study partner in this study, during which the rater or clinician will ask to the study partner open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills (up to 6 years only) and used to calculate the Vineland-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning.	Weeks 12 and 24
Secondary	Change From Baseline at Weeks 12 and 24 on the Vineland-II Daily Living Skills Domain Standard Score	The Vineland-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable study partner in this study, during which the rater or clinician will ask to the study partner open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills (up to 6 years only) and used to calculate the Vineland-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning.; Only descriptive statistics presented instead of the planned estimated due to the early discontinuation of the study due to futility.	Weeks 12 and 24
Secondary	Change From Baseline in Severity of Clinical Impressions as Measured by Clinical Global Impression-Severity (CGI-S)	The CGI-S reflects the rater's impression of the subject's current autism severity on a 7-point scale ranging from no symptoms (1) to very severe symptoms (7). Changes in CGI-S score were calculated as increase or decrease in absolute CGI-S scores between Baseline and Weeks 12 and 24. Percentage of participants reported for each change in score from baseline.	Weeks 12 and 24
Secondary	Improvements in Clinical Impressions, as Measured by Clinical Global Impression-Improvement (CGI-I)	This is a 7-point Likert scale that assesses improvement of the patient's condition. Scores range from the worst score of 7 (Very much worse) to the best score of 1 (Very much improved). Lower scores are better on this scale, and indicate greater improvement. Percentage of participants reported for each score.	Weeks 12 and 24
Secondary	Change From Baseline at Weeks 12 and 24 in the Hamilton Anxiety Rating Scale (HAM-A) Total and Domain Scores	The HAM-A is a 14-item, rater administered interview, assessing the severity of anxiety symptoms during the past 7 days. Seven items assess psychic anxiety and seven assess somatic anxiety. Each item utilizes a 5-point symptom severity response scale, ranging from none (0) to very severe (4). A total score is calculated that ranges from 0 to 56; higher scores are indicative of more severe anxiety.	Weeks 12 and 24
Secondary	Proportion of Subjects With a >=6-point Improvement in Vineland-II 2DC Score	The Vineland-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable study partner in this study, during which the rater or clinician will ask to the study partner open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills (up to 6 years only) and used to calculate the Vineland-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning; All participants who have an improvement of at least 6 points are included in the >=6 score threshold	Weeks 12 and 24
Secondary	Percentage of Participants With Adverse Events	According to the ICH guideline for Good Clinical Practice, an adverse event is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution.; The Blinded Treatment Period continued for 24 weeks, Open Label Extension (OLE) Treatment Period continued up to 2 years. The study was pre-maturely terminated, therefore did not reach the planned end date.	Week 24 and Up to Approximately 2 Years