A Double-blind, Randomized, Placebo-controlled Trial of Adjunctive Ganaxolone Treatment in Children and Young Adults With Cyclin-dependent Kinase-like 5 (CDKL5) Deficiency Disorder (CDD) Followed by Long-term Open-label Treatment
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 101
- 试验地点
- 2
- 主要终点
- Summary of 28-day Seizure Frequency for Major Motor Seizure Types
研究概览
简要总结
A clinical study to evaluate the efficacy, safety, and tolerability of adjunctive ganaxolone therapy compared to placebo for the treatment of seizures in children and young adults with genetically confirmed CDKL5 gene mutation.
详细描述
The Marigold Study is a global, double-blind, placebo-controlled, Phase 3 clinical trial that will enroll approximately 70 patients between the ages of 2 and 21 with a confirmed disease-related CDKL5 gene variant. Patients will undergo a baseline period before being randomized to receive, in addition to their existing anti-seizure treatment, either ganaxolone or placebo for 17 weeks. Following the treatment period, all patients that meet certain eligibility requirements will have the opportunity to receive ganaxolone in the open label phase of the study. The study's primary efficacy endpoint is percent reduction in seizures. Secondary outcome measures will include non-seizure-related endpoints to capture certain behavioral and sleep disturbances that have been seen in previous clinical studies with ganaxolone.
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
- 2 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Genetically confirmed CDKL5 gene mutation, seizure onset by 1 year of age and lack of independent ambulation by 2 years of age
- •Failure to control seizures despite 2 or more anti-seizure medications
- •At least 16 seizures per 28 days of primary seizure types
- •On a stable regimen of 0-4 anti-seizure medications (Vagus nerve stimulator, ketogenic diet, and modified Atkins diet do not count towards this limit)
- •Additional Inclusion Criteria apply and can be discussed with study team
排除标准
- •Previous exposure to ganaxolone
- •West Syndrome with hypsarrhythmia pattern on EEG or seizures predominantly of Infantile Spasms type
- •Use of adrenocorticotropic hormone (ACTH), prednisone or other glucocorticoid or use of moderate or strong inducers or inhibitors of CYP3A4/5/7 are prohibited
- •Use of tetrahydrocannabinol (THC) or cannabidiol (CBD) is prohibited during the double-blind phase, unless patient has a prescription of Epidiolex®
- •Exposure to any other investigational drug within 30 days or fewer than 5 half-lives prior to screening
- •Plasma allopregnanolone-sulfate (Allo-S) levels greater than or equal to 6.0 ng/ml at screening visit
- •Additional Exclusion Criteria apply and can be discussed with study team
研究组 & 干预措施
Ganaxolone
ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks
干预措施: ganaxolone (Drug)
Placebo
placebo suspension 3x's /day for 17 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Summary of 28-day Seizure Frequency for Major Motor Seizure Types
时间窗: End of the double-blind 17 week treatment period
Summary of 28-day seizure frequency for Major Motor Seizure Types during the double-blind treatment period relative to the 6-week prospective baseline period Note: Summaries are based on the sum of the individual seizures, the countable seizures, and the clusters with uncountable seizures (each cluster with uncountable seizures counts as 1 seizure). Within the baseline and post baseline intervals, 28-day seizure frequency was calculated as the total number of seizures in the interval divided by the number of days with available seizure data in the interval, multiplied by 28.
次要结局
- Caregiver Global Impression of Change in Attention(End of the double-blind 17 week treatment period)
- Caregiver Global Impression of Change in Target Behavior(End of the double-blind 17 week treatment period)
- Clinical Global Impression of Improvement - Clinician([Time Frame: End of the double-blind 17 week treatment period])
- Clinical Global Impression of Improvement - Parent/Caregiver(End of the double-blind 17 week treatment period)
- Percentage of Seizure-free Days for Major Motor Seizure Types(End of the double-blind 17 week treatment period)
- Arithmetic Change in Longest Seizure Free Interval, Based on Primary Seizure Types(End of the double-blind 17 week treatment period)
- Caregiver Global Impression of Change in Seizure Intensity and Duration(End of the double-blind 17 week treatment period)