A Phase II Multi-Center, Randomized, Double-Blind, 24-Week, Parallel Group, Placebo-Controlled Study to Investigate the Efficacy and Safety of Balovaptan (RO5285119) in Children and Adolescents Age 5-17 With Autism Spectrum Disorder (ASD)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 339
- 试验地点
- 45
- 主要终点
- Change From Baseline in Vineland™-II Adaptive Behavior Scale Two Domain Composite (2DC) Score at Week 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
研究概览
简要总结
For participants enrolled prior to Version 6 of the protocol: This was a Phase II multi-center, randomized, double-blind, 24-week, 3-arm, parallel group, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of balovaptan in children and adolescents aged 5-17 years with ASD who are high functioning (intelligence quotient [IQ] greater than or equal to [>=] 70).
For participants enrolled according to Version 6 of the protocol: This was a Phase II multi-center, randomized, double-blind, 24-week, parallel group, placebo-controlled, 2-arm study with participants assigned either to a 10 milligram (mg) or equivalent dose of balovaptan, or placebo. All other study parameters remained as stated above.
There are three parts to this study: PK Part (Study part 1) included up to 8 weeks of treatment, Main Treatment Part (Study part 2) included 24 week of treatment, and the Open Label Extension Part (Study part 3) included Week 24 to Week 76 of treatment.
All participants that completed the 24-week treatment period were eligible to participate in an optional 52-week open-label extension (OLE) during which they received balovaptan treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fluent in English
- •Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for ASD or International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD10) criteria for Autism diagnosis confirmed by Autism Diagnostic Observational Schedule (ADOS-2) criteria
- •Social Responsiveness Scale, second edition (SRS-2) (T-score) >= 66
- •Clinical Global Impressions of Severity (CGI-S) >= 4 (moderately ill) at screening
- •IQ >= 70 as assessed by Wechsler Abbreviated Scale of Intelligence Scale: Second Edition (WASI-II) or Wechsler Preschool and Primary Scale of Intelligence: Fourth Edition (WPPSI-IV) intelligence test
- •Language, hearing, and vision compatible with the study measurements as judged by the investigator
- •Inclusion Criteria for the OLE:
- •Have completed the blinded treatment phase of the study OR were required to stop dosing at or before Week 8
- •Have no adverse events that would prohibit starting the OLE
排除标准
- •Initiation of a major change in psychosocial intervention (including investigational) within 4 weeks prior to screening
- •Unstable or uncontrolled clinically significant psychiatric and/or neurological disorder that may interfere with the safety or efficacy endpoints
- •Known personal or family history of cerebral aneurysm
- •Risk of suicidal behavior
- •Seizure within the past 6 months
- •Medical history of alcohol or substance abuse/dependence
- •Concurrent cardio-vascular disease not considered well controlled by the Investigator
- •Clinically significant abnormality on electrocardiogram at screening
- •Concomitant disease or condition (pulmonary, gastro-intestinal, hepatic, renal, metabolic, immunological system, or obesity that could interfere with the conduct of the study
- •Evidence for current gastro-intestinal bleeding, e.g., active stomach ulcer disease
- •History of coagulopathies, bleeding disorders, or blood dyscrasias
- •Positive serology for hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) 1, or HIV 2
- •Confirmed clinically significant abnormality in parameters of hematology, clinical chemistry, coagulation, or urinalysis
- •Medical history of malignancy if not considered cured
- •Participation in an investigational drug study within 90 days or 5 times the half-life of the investigational molecule (whichever is longer) prior to randomization
- •Loss of blood over 250 milliliters within three months prior to screening
- •Allowed medications have not been stable since 4 weeks before screening, and allowed medications for treatment of epilepsy have not been stable since 3 months before screening
- •Use of prohibited medications within 2 weeks prior to screening visit or 5 times the half-life prior to randomization (whichever is longer)
研究组 & 干预措施
Placebo
Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
干预措施: Placebo (Drug)
Balovaptan (RO5285119) 10 mg/d equivalent
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks (up to 52 additional weeks for those enrolled in the OLE).
干预措施: RO5285119 (Drug)
Balovaptan (RO5285119) 4 mg/d equivalent
Participants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 mg/d of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks. This arm is open only to those participants enrolled prior to Version 6 of the study protocol.
干预措施: RO5285119 (Drug)
结局指标
主要结局
Change From Baseline in Vineland™-II Adaptive Behavior Scale Two Domain Composite (2DC) Score at Week 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo
时间窗: Baseline, 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 caregiver in this study, during which the rater or clinician will ask to the caregiver 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. Mixed model with repeated measures (MMRM) was used for analysis with assessments at baseline, week 12 and week 24.
次要结局
- Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo(Baseline, Weeks 12 and 24)
- Change From Baseline in Vineland™-II Composite Standard Score After 12 Weeks and 24 Weeks of Treatment for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo(Baseline, Weeks 12 and 24)
- Change From Baseline in Vineland™-II Adaptive Behavior Scale Communication, Socialization, and Daily Living Skills Domain Standard Scores at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo(Baseline, Weeks 12 and 24)
- Percentage of Participants With Adverse Events for Treatment With Balovaptan(Baseline to Week 24 and up to Week 76)
- Proportion of Subjects With >=6 Points Improvement in the Vineland-II 2DC Score for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo(Baseline, Weeks 12 and 24)
- Change From Baseline in Ohio Autism Clinical Impressions Scale-Severity (OACIS-S) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo(Baseline, Weeks 12 and 24)
- Clinical Global Impressions- Improvement (CGI-I) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo(Weeks 12 and 24)
- Ohio Autism Clinical Impressions Scale- Improvement (OACIS-I) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo(Weeks 12 and 24)
- Change From Baseline in Patient-Reported Pediatric Quality of Life (PedsQL) v4.0 Generic Core Scale After 12 Weeks and 24 Weeks of Treatment for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo(Baseline, Weeks 12 and 24)
- Change From Baseline in Vineland-II Composite Standard Score in Adolescents and Children Independently at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo(Baseline, Weeks 12 and 24)
- Change From Baseline in Vineland-II Adaptive Behavior Scale 2DC Score at Week 12 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo(Baseline, Week 12)