E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
ASD is a neurodevelopmental disorder that impairs the ability to communicate and interact |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063844 |
E.1.2 | Term | Autism spectrum disorder |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003805 |
E.1.2 | Term | Autism |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034739 |
E.1.2 | Term | Pervasive developmental disorder NOS |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of 10 mg of balovaptan compared with placebo based on the Vineland TM-II two-domain composite (2DC) score |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of 10 mg of balovaptan compared with placebo based on the Vineland-II 2DC score, Pediatric Quality of Life Inventory TM Generic Core Scales(PedsQLTM), Version 4.0, summary and total scores, Vineland-II composite standard score, Vineland-II Socialization, Communication, Daily Living Skills domain standard scores, Clinical Global Impressions(CGI) –Severity(S) and Improvement(I), Hamilton Anxiety Rating Scale (HAM-A) total and domain scores |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Males or females, age 18 years or older
- Subject meets the Diagnostic and Statistical Manual of Mental Disorders, Version 5 (DSM-5) criteria for ASD for an autism diagnosis and is confirmed using Autism Diagnostic Observation Schedule (ADOS)-2 criteria
- Social Responsiveness Scale (SRS)-2, proxy version, total t score >=66 at screening
- A full scale IQ score >=70 on the Wechsler Abbreviated Scale of Intelligence®-II
- Ability and willingness to fully comply with study visit schedule and regular assessments and fluency in the language of the site
- Subject’s participation in the study or discontinuation of prohibited medication will not pose undue risks to the subject, in the investigator’s opinion
- 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 30 days after the last dose of study drug
- Treatment with permitted medications and behavioral therapy regimens, with the intent that such treatments remain stable throughout the study and with no expected changes before the Week 24 visit |
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E.4 | Principal exclusion criteria |
General Exclusion Criteria
- Pregnancy or breastfeeding, or intention to become pregnant during the study
Neurologic and Psychiatric Exclusion Criteria
- 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 (including Alcohol or substance abuse or dependence disorder) during the last 12 months, as defined by the DSM-5 criteria
- 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
Exclusions Related to Cardiovascular Disorders
- 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 (ULN) of CK MB (electrophoretic measurement), high sensitivity cardiac troponin T (hs cTnT), cardiac troponin I (cTnI), and/or N-terminal pro B-type natriuretic peptide (NT proBNP)
Exclusions Related to Other Organ Systems
- 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, 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, clinical chemistry, coagulation, or urinalysis
- Medical history of malignancy, if not considered cured
Additional Exclusion Criteria
- Allowed medications have not been stable for 12 weeks prior to screening
- Previous treatment with prohibited medications or herbal remedies within 2 weeks prior to randomization or 5 half-lives
- Blood donation or loss of blood > 500 mL within 3 months prior to randomization
- Previous participation in an investigational drug or device study within 60 days prior to randomization or previous enrollment in investigational trials of balovaptan |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change from baseline at Week 24 on the Vineland TM -II 2DC score |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Baseline (Day 1) and Week 24 |
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E.5.2 | Secondary end point(s) |
1. Change from baseline at Week 12 on the Vineland-II 2DC score
2. Change from baseline at Weeks 12 and 24 in the PedsQLTM Core module, Version 4.0, on summary and total scores
3. Change from baseline at Weeks 12 and 24 in the Vineland-II a composite standard score
4. Change from baseline at Weeks 12 and 24 in Vineland-II Socialization domain standard score
5. Change from baseline at Weeks 12 and 24 in Vineland-II Communication domain standard score
6. Change from baseline at Weeks 12 and 24 in Vineland-II Daily Living Skills domain standard score
7. Change from baseline in severity of clinical impressions as measured by CGI-S after 12 weeks and 24 weeks of treatment
8. Improvements in clinical impressions, as measured by CGI-I after 12 weeks and 24 weeks of treatment
9. Change from baseline in the HAM-A total and domain scores at Weeks 12 and 24
10. Proportion of subjects with a >=6-point improvement in Vineland-II 2DC score at Weeks 12 and 24 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Baseline and Week 12
2-6. Baseline, Week 12 and Week 24
7-8. Week 12 and Week 24
9-10. Baseline, Week 12 and Week 24 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
2 year open label extension |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Germany |
Italy |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The date when the last subject, last visit occurs in the open-label extension period or the follow-up period.
It is anticipated that it may take from 18 to 28 months to recruit all subjects for the study. Hence, the total length of the study is estimated to be approximately 4-5 years. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |