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

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ClinicalTrials.gov Identifier: NCT03504917
Recruitment Status : Terminated (A futility analysis assessed that the study is highly unlikely to meet the pre-defined primary objective of the study. No new safety concerns were identified.)
First Posted : April 20, 2018
Results First Posted : May 7, 2021
Last Update Posted : June 22, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE April 12, 2018
First Posted Date  ICMJE April 20, 2018
Results First Submitted Date  ICMJE March 2, 2021
Results First Posted Date  ICMJE May 7, 2021
Last Update Posted Date June 22, 2021
Actual Study Start Date  ICMJE August 8, 2018
Actual Primary Completion Date March 4, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2021)
Change From Baseline at Week 24 on the Vineland Adaptive Behavior Scales (Vineland-II) Two-domain Composite (2DC) Score. [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 12, 2018)
Change from baseline at Week 24 on the Vineland Adaptive Behavior Scales (Vineland-II) two-domain composite (2DC) score [ Time Frame: Baseline, Week 24 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2021)
  • Change From Baseline at Week 12 on the Vineland-II 2DC Score [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 Communication Domain Standard Score [ Time Frame: 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.
  • Change From Baseline at Weeks 12 and 24 on the Vineland-II Daily Living Skills Domain Standard Score [ Time Frame: 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 in Severity of Clinical Impressions as Measured by Clinical Global Impression-Severity (CGI-S) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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.
  • Proportion of Subjects With a >=6-point Improvement in Vineland-II 2DC Score [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2018)
  • Change From Baseline at Week 12 on the Vineland-II 2DC Score [ Time Frame: Baseline, Weeks 12 ]
  • 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 [ Time Frame: Baseline, Weeks 12 and 24 ]
  • Change from baseline at Weeks 12 and 24 in the Vineland-II A composite standard score [ Time Frame: Baseline, Weeks 12 and 24 ]
  • Change From Baseline at Week 12 and 24 on the Vineland-II Socialization Domain Standard Score [ Time Frame: Baseline, Weeks 12 and 24 ]
  • Change From Baseline at Weeks 12 and 24 on the Vineland-II Communication Domain Standard Score [ Time Frame: Baseline, Weeks 12 and 24 ]
  • Change From Baseline at Weeks 12 and 24 on the Vineland-II Daily Living Skills Domain Standard Score [ Time Frame: Baseline, Weeks 12 and 24 ]
  • Change From Baseline in Severity of Clinical Impressions as Measured by Clinical Global Impression-Severity (CGI-S) [ Time Frame: Baseline, After 12 weeks and 24 weeks ]
  • Improvements in Clinical Impressions, as Measured by Clinical Global Impression-Improvement (CGI-I) [ Time Frame: After 12 weeks and 24 weeks of treatment ]
  • Change From Baseline at Weeks 12 and 24 in the Hamilton Anxiety Rating Scale (HAM-A) Total and Domain Scores [ Time Frame: Baseline, Weeks 12 and 24 ]
  • Proportion of Subjects With a >=6-point Improvement in Vineland-II 2DC Score [ Time Frame: Weeks 12 and 24 ]
  • Area Under the Concentration-time Curve of RO5285119 in Plasma at Steady State Over 24 Hours (AUC0-24,ss) [ Time Frame: Weeks 2, 8, 12, 20, 24 or early termination ]
  • Maximum plasma concentration [ Time Frame: Weeks 2, 8, 12, 20, 24 or early termination ]
  • Apparent Clearance (CL) of RO5285119 [ Time Frame: Weeks 2, 8, 12, 20, 24 or early termination ]
  • Volume of Distribution (VD) of RO5285119 [ Time Frame: Weeks 2, 8, 12, 20, 24 or early termination ]
  • Plasma concentration of M2 metabolites (as applicable) [ Time Frame: Weeks 2, 8, 12, 20, 24 or early termination ]
  • Plasma concentrations of M3 metabolites [ Time Frame: Weeks 2, 8, 12, 20, 24 or early termination ]
  • Ratios of metabolite to parent drug concentration at trough [ Time Frame: Weeks 2, 8, 12, 20, 24 or early termination ]
  • Percentage of Participants With Adverse Events [ Time Frame: Week 24 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Autism Spectrum Disorder
Intervention  ICMJE
  • Drug: Balovaptan
    Participants will receive 10 mg of oral administration balovaptan once a day (QD).
  • Drug: Placebo
    Participants will receive matching placebo.
Study Arms  ICMJE
  • Experimental: Balovaptan
    Intervention: Drug: Balovaptan
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 11, 2020)
322
Original Estimated Enrollment  ICMJE
 (submitted: April 12, 2018)
350
Actual Study Completion Date  ICMJE July 1, 2020
Actual Primary Completion Date March 4, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   France,   Italy,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03504917
Other Study ID Numbers  ICMJE WN39434
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP