A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| 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 : October 27, 2021
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Autism Spectrum Disorder | Drug: Balovaptan Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 322 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | August 8, 2018 |
| Actual Primary Completion Date : | March 4, 2020 |
| Actual Study Completion Date : | July 1, 2020 |
| Arm | Intervention/treatment |
|---|---|
| Experimental: Balovaptan |
Drug: Balovaptan
Participants will receive 10 mg of oral administration balovaptan once a day (QD). |
| Placebo Comparator: Placebo |
Drug: Placebo
Participants will receive matching placebo. |
- 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.
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03504917
Show 51 study locations
| Study Director: | Clinical Trials | Hoffmann-La Roche |
Documents provided by Hoffmann-La Roche:
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT03504917 |
| Other Study ID Numbers: |
WN39434 |
| First Posted: | April 20, 2018 Key Record Dates |
| Results First Posted: | May 7, 2021 |
| Last Update Posted: | October 27, 2021 |
| Last Verified: | October 2021 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
|
Autistic Disorder Autism Spectrum Disorder Child Development Disorders, Pervasive Neurodevelopmental Disorders Mental Disorders |
Balovaptan Antidiuretic Hormone Receptor Antagonists Molecular Mechanisms of Pharmacological Action Natriuretic Agents Physiological Effects of Drugs |