A Randomized, Double-Blind, Placebo-Controlled Study of TEV-50717 (Deutetrabenazine) for the Treatment of Dyskinesia in Cerebral Palsy in Children and Adolescents
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 70
- 主要终点
- Change From Baseline in the Movement Disorder-Childhood Rating Scale (MD-CRS) Part II Total Score (Movement Disorder Severity, Centrally Read) at Week 15
研究概览
简要总结
CP (cerebral palsy) refers to a group of neurological disorders that appear in infancy or early childhood and permanently affect body movement and muscle coordination. CP is caused by damage to or abnormalities inside the developing brain that disrupt the brain's ability to control movement and maintain posture and balance. The signs of CP usually appear in the early months of life, although specific diagnosis may be delayed until the age of 2 years or older. TEV-50717 (deutetrabenazine, also known as SD-809) has already provided evidence for safe and effective use in 2 other hyperkinetic movement disorders, namely chorea in Huntington's disease (HD) and tardive dyskinesia (TD). Currently, there is no approved treatment available for Dyskinesia in cerebral palsy (DCP). The available treatment options address some of the manifestations of DCP. The study population will include pediatric and adolescent participants (6 through 18 years of age) with DCP with predominant choreiform movement disorder, who have had nonprogressive CP symptoms since infancy (≤2 years of age). Diagnosis of DCP is based on the Surveillance of Cerebral Palsy in Europe criteria.
This is a Phase 3 study that will evaluate the efficacy and safety of TEV-50717 administered as oral tablets at a starting dose of 6 mg once daily in participants (age 6 through 18 years, inclusive) with DCP with predominant choreiform movement disorder. The study will be conducted in multiple centers and will use 2 parallel treatment groups (ie, TEV-50717 and placebo) in which participants will be randomized in a 2:1 ratio.
"Predominant" in this instance indicates that the choreiform movement disorder is the main cause of impairment or distress.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant is 6 through 18 years of age (inclusive) at baseline.
- •Participant weighs at least 26 pounds (12 kg) at baseline.
- •Participant has had CP symptoms since infancy (≤2 years)
- •Choreiform is the prevalent movement disorder as assessed by the EAB at screening.
- •Participant has a diagnosis of DCP
- •Participant is able to swallow study medication whole.
- •Females who are postmenarchal or ≥12 years of age whose male partners are potentially fertile (ie, no vasectomy) must use highly effective birth control methods for the duration of the study
- •Additional criteria apply, please contact the investigator for more information
排除标准
- •Participant has a predominant movement disorder other than dyskinesia.
- •Participant's predominant motor symptoms are dystonic.
- •Participant's predominant motor symptoms are spastic.
- •Participant has choreiform movement disorder that has not been consistent throughout the life of the participant.
- •Participant has clinically significant depression at screening or baseline.
- •Note: Participants receiving antidepressant therapy may be enrolled if on a stable dose for at least 6 weeks before screening.
- •Participant has a history of suicidal intent or related behaviors within 2 years of screening:
- •Previous intent to act on suicidal ideation with a specific plan, irrespective of level of ambivalence, at the time of suicidal thought
- •Previous suicidal preparatory acts or behavior
- •Participant has a history of a previous actual, interrupted, or aborted suicide attempt.
- •Participant has a first-degree relative who has completed suicide.
- •Participant has received treatment with stem cells, deep brain stimulation, transmagnetic stimulation, or transcranial direct current stimulation for treatment of abnormal movements or CP within 6 months of the screening visit, or the participant is not in a stable clinical condition.
- •Participant has recent surgical procedure or is anticipated to have a surgical procedure during the study that, in the opinion of the investigator, makes the Participant unsuitable for the study.
- •Participant has a severe mental disability or an unstable or serious medical illness (eg, epilepsy) at screening or baseline that, in the opinion of the investigator, could jeopardize or would compromise the Participant's ability to participate in this study.
- •Participant has a known allergy to any of the components of the investigational medicinal product (IMP).
- •Participant is pregnant or breastfeeding.
- •Participant has a history of or acknowledges alcohol or substance abuse in the 12 months before screening
- •Participants with a history of torsade de pointes, congenital long QT syndrome, bradyarrhythmias, other cardiac arrhythmias, or uncompensated heart failure.
- •Additional criteria apply, please contact the investigator for more information
研究组 & 干预措施
TEV-50717
administered as oral tablets at a starting dose of 6 mg once daily
干预措施: TEV-50717 (Drug)
Placebo
Matching placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in the Movement Disorder-Childhood Rating Scale (MD-CRS) Part II Total Score (Movement Disorder Severity, Centrally Read) at Week 15
时间窗: Baseline, Week 15
MD-CRS part II evaluates the severity of movement disorder in a scale of 0 to 4 in 7 body regions, all areas in which dyskinesia can be seen. All items were scored by the rater in the clinic and were centrally read based on video recording. In rating the movement disorder of body part, 0 refers to absence of a movement disorder and 4 refers to a situation where movement disorder is present during all of the tasks for the region examined and/or involves 3 or more of the other regions, making completion impossible. The 7 body regions are (i) eye and periorbital region, (ii) face, (iii) tongue and perioral region, (iv) neck, (v) trunk, (vi) upper limb, and (vii) lower limb. Total score was obtained by summing the individual items scores and ranges from 0 (absent of a movement disorder) to 28 (marked/prolonged movement disorder), with higher scores indicating more movement disorder. Least square (LS) mean and standard error (SE) was calculated using a mixed-model repeated-measures (MMRM).
次要结局
- Change From Baseline in the MD-CRS Part I Total Score (General Assessment, Centrally Read) at Week 15(Baseline, Week 15)
- Change From Baseline in Unified Huntington's Disease Rating Scale-Total Maximal Dystonia (UHDRS-TMD) Score (Centrally Read) at Week 15(Baseline, Week 15)
- Change From Baseline in the MD-CRS Part I Total Score (General Assessment, Physician Rated) at Week 15(Baseline, Week 15)
- Change From Baseline in UHDRS-TMC Score (Physician Rated) at Week 15(Baseline, Week 15)
- Clinical Global Impression of Improvement (CGI-I) Scale Score (Global, Physician Rated) at Week 15(Week 15)
- Caregiver Global Impression of Improvement (CaGI-I) Scale Score (Global, Caregiver Rated) at Week 15(Week 15)
- Change From Baseline in Unified Huntington's Disease Rating Scale-Total Maximal Chorea (UHDRS-TMC) Score (Centrally Read) at Week 15(Baseline, Week 15)
- Change From Baseline in the MD-CRS Part II Total Score (General Assessment, Physician Rated) at Week 15(Baseline, Week 15)
- Change From Baseline in MD-CRS Global Index Score (Calculated From MD-CRS Parts I and II Total Scores, Centrally Read) at Week 15(Baseline, Week 15)
- Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) Subscale I Total Score at Week 15(Baseline, Week 15)
- Change From Baseline in Extrapyramidal Symptom Rating Scale (ESRS) Subscale II Total Score at Week 15(Baseline, Week 15)
- Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 15(Baseline, Week 15)
- Change From Baseline in MD-CRS Global Index Score (Calculated From MD-CRS Parts I and II Total Scores, Physician Rated) at Week 15(Baseline, Week 15)
- Change From Baseline in UHDRS-TMS Score (Physician Rated) at Week 15(Baseline, Week 15)
- Change From Baseline in UHDRS-TMD Score (Physician Rated) at Week 15(Baseline, Week 15)
- Change From Baseline in the CP Module of the Pediatric Quality of Life Inventory (PedsQL) Total Score (Quality of Life [QoL], Participant/Caregiver) at Week 15(Baseline, Week 15)
- Number of Participants With CGI-I Response(Week 15)
- Change From Baseline in Pediatric Evaluation Disability Inventory-Computer Adapted Test (PEDI-CAT) Score (Activities of Daily Living [ADL], Caregiver Completed, Content-Balanced Version) at Week 15(Baseline, Week 15)
- Patient Global Impression of Improvement (PGI-I) Scale Score (Global, Participant/Caregiver) at Week 15(Week 15)
- Number of Participants With CaGI-I Response(Week 15)
- Number of Participants With CGI-S Response(Week 15)
- Change From Baseline in Clinical Global Impression of Severity (CGI-S) Scale Score (Global, Physician Rated) at Week 15(Baseline, Week 15)
- Number of Participants With PGI-I Response(Week 15)
- Number of Participants With Adverse Events (AEs)(Baseline up to Week 17)
- Number of Participants With Shift From Baseline to Week 15 in Electrocardiogram (ECG) Findings(Baseline to Week 15)
- Change From Baseline in Child Behavior Checklist (CBCL) Competence Total Score at Week 15(Baseline, Week 15)
- Change From Baseline in Child Behavior Checklist (CBCL) Syndrome Total Score at Week 15(Baseline, Week 15)
- Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Outcomes (Suicidal Ideation and Suicidal Behavior) at Week 15(Week 15)