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

Phase 3

Terminated

Conditions: Autism Spectrum Disorder

Interventions: Drug: Placebo
Drug: Balovaptan

Registration Number: NCT03504917

Lead Sponsor: Hoffmann-La Roche

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 322

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Balovaptan	Balovaptan	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline at Week 24 on the Vineland Adaptive Behavior Scales (Vineland-II) Two-domain Composite (2DC) Score.	Week 24	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Severity of Clinical Impressions as Measured by Clinical Global Impression-Severity (CGI-S)	Weeks 12 and 24	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.
Improvements in Clinical Impressions, as Measured by Clinical Global Impression-Improvement (CGI-I)	Weeks 12 and 24	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.
Change From Baseline at Weeks 12 and 24 in the Hamilton Anxiety Rating Scale (HAM-A) Total and Domain Scores	Weeks 12 and 24	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.
Change From Baseline at Week 12 on the Vineland-II 2DC Score	Week 12	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.
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	Weeks 12 and 24	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.
Change From Baseline at Weeks 12 and 24 in the Vineland-II Adaptive Behavior Composite Standard Score	Weeks 12 and 24	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.
Change From Baseline at Week 12 and 24 on the Vineland-II Socialization Domain Standard Score	Baseline, Weeks 12 and 24	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.
Change From Baseline at Weeks 12 and 24 on the Vineland-II Daily Living Skills Domain Standard Score	Weeks 12 and 24	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.
Change From Baseline at Weeks 12 and 24 on the Vineland-II Communication Domain Standard Score	Weeks 12 and 24	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.
Proportion of Subjects With a >=6-point Improvement in Vineland-II 2DC Score	Weeks 12 and 24	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
Percentage of Participants With Adverse Events	Week 24 and Up to Approximately 2 Years	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.

Trial Locations

Locations (51): Woodland Research Northwest, LLC
🇺🇸
Rogers, Arkansas, United States
MCB Clinical Research Centers
🇺🇸
Colorado Springs, Colorado, United States
Millennium Psychiatric Associates, LLC
🇺🇸
Saint Louis, Missouri, United States
Nathan S. Kline Institute for Psychiatric Research
🇺🇸
Orangeburg, New York, United States
ASL TO2; Centro Pilota Regione Piemonte - Dip. Salute Mentale
🇮🇹
Torino, Piemonte, Italy
IMIC Inc.
🇺🇸
Palmetto Bay, Florida, United States
Hopital Charles Perrens; Centre de Ressources Autisme Aquitaine
🇫🇷
Bordeaux, France
Center for Autism and the Developing Brain
🇺🇸
New York, New York, United States
Kings College Hospital; Kings Clinical Research Facility
🇬🇧
London, United Kingdom
Centre hospitalier du Rouvray; CRAHN Centre de Ressources Autisme Haute-Normandie
🇫🇷
Sotteville Les Rouen, France
AUSL di Piacenza; Psichiatria di Collegamento
🇮🇹
Piacenza, Lombardia, Italy
Northwest Clinical Research Center
🇺🇸
Bellevue, Washington, United States
Hapworth Research Inc.
🇺🇸
New York, New York, United States
ASST di Pavia; Dip. di Scienze del Sistema Nervoso e del Comportamento
🇮🇹
Pavia, Lombardia, Italy
McGill University Health Centre - Glen Site
🇨🇦
Montreal, Quebec, Canada
Hospital General Universitario Gregorio Marañon; Servicio de Psiquiatria del niño y del adolescente
🇪🇸
Madrid, Spain
Okanagan Clinical Trials
🇨🇦
Kelowna, British Columbia, Canada
A.O.U. Policlinico - V. Emanuele - P.O. Gaspare Rodolico; Dip. Terapia integrata disturbi resistenti
🇮🇹
Catania, Sicilia, Italy
Hospital Universitario Rio Hortega; Departamento de Psiquiatria
🇪🇸
Valladolid, Spain
Hospital Universitari Vall d'Hebron; Sevicio de Psiquiatría
🇪🇸
Barcelona, Spain
Western General Hospital; Wellcome Trust CRF
🇬🇧
Edinburgh, United Kingdom
Holland Bloorview Kids Rehabilitation Hospital; Autism Research Centre
🇨🇦
East York, Ontario, Canada
Queen Elizabeth University Hospital; Clinical Research Facility
🇬🇧
Glasgow, United Kingdom
Lake Charles Clinical Trials, LLC
🇺🇸
Lake Charles, Louisiana, United States
Hospices Civils de Lyon; Centre d'Investigation Clinique Pédiatrique
🇫🇷
LYON Cedex, France
Aspen Clinical Research
🇺🇸
Orem, Utah, United States
University of Western Ontario
🇨🇦
London, Ontario, Canada
Hospital Mutua de Terrassa; Departamento de Psiquiatria
🇪🇸
Terrassa, Barcelona, Spain
RE:Cognition Health; RE:Cognition Health
🇬🇧
London, United Kingdom
Harmonex Neuroscience Research
🇺🇸
Dothan, Alabama, United States
Southwest Autism Research & Resource Center
🇺🇸
Phoenix, Arizona, United States
University of California , Los Angeles (UCLA); Child, Adolescent Psychiatry
🇺🇸
Los Angeles, California, United States
PCSD Feighner Research
🇺🇸
San Diego, California, United States
University of California at San Francisco
🇺🇸
San Francisco, California, United States
Yale University / Yale-New Haven Hospital
🇺🇸
New Haven, Connecticut, United States
Sarkis Clinical Trials
🇺🇸
Gainesville, Florida, United States
University Hospitals
🇺🇸
Cleveland, Ohio, United States
Ohio State University
🇺🇸
Columbus, Ohio, United States
APG- Advanced Psychiatric Group
🇺🇸
Orlando, Florida, United States
Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Uni of Chicago; Centre For Advanced Medicine
🇺🇸
Chicago, Illinois, United States
Richmond Behavioral Associates
🇺🇸
Staten Island, New York, United States
The Johns Hopkins Hospital
🇺🇸
Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
University of Minnesota Medical Center-Fairview
🇺🇸
Minneapolis, Minnesota, United States
Cutting Edge Research Group
🇺🇸
Oklahoma City, Oklahoma, United States
UPMC Western Psychiatric Institute and Clinic
🇺🇸
Pittsburgh, Pennsylvania, United States
Vanderbilt University Medical Center; Department of Psychiatry
🇺🇸
Nashville, Tennessee, United States
BioBehavioral Research of Austin, PC
🇺🇸
Austin, Texas, United States
Red Oak Psychiatry Associates, PA
🇺🇸
Houston, Texas, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States