A Double-blind, Placebo-controlled, Dose-ranging Clinical Study to Evaluate the Safety, Tolerability, and Antiepileptic Activity of Ganaxolone in Treatment of Patients With Infantile Spasms
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 15
- 主要终点
- Change From Baseline in Frequency of Spasm Clusters at Day 10
研究概览
简要总结
The study consists of cohorts where participants are randomized, in a 2:1 ratio, to 1 of 2 sequences, A and B. In each cohort, Sequence A, comprised of participants, who will receive ascending doses of ganaxolone and ascending doses of placebo. Sequence B, comprised of participants, who will receive ascending doses of placebo and ascending doses of ganaxolone. The dosing level in each subsequent cohort will be based upon experience gained from previous cohorts.
详细描述
Male or female, 4 to 24 months of age (inclusive) with a diagnosis of IS with a 24 hour video EEG (vEEG) recording confirming the diagnosis and previously treated with 3 or fewer antiepileptic drugs (AEDs) are eligible for the study. The subject is able to continue treatment with concomitant AEDs (no more than 2; adrenocorticotropic hormone [ACTH], corticosteroids, felbamate, and vigabatrin are not allowed concomitantly). A ketogenic diet is permitted if it can be maintained for the duration of the study.
There will be a total of three weekly 24-hr video EEGs (baseline, end of weeks 1 and 2 of treatment). Dosing titration begins the day after each video EEG during the inpatient stay. All subjects will be receiving ganaxolone the day after the second video EEG.
A Data Monitoring Board (DMB) will determine whether successive cohorts of subjects can be dosed at an increased dose level; up to a maximum of 6 cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 4 Months 至 24 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be diagnosed with IS (regardless of etiology- except for a progressive neurologic illness). Diagnostic Criteria: Seizures consisting of single or repetitive short muscular contractions leading to flexion or extension. Spasms may be characterized as tonic or myoclonic contractions, may occur singly or in clusters, and typically occur bilaterally and symmetrically. The EEG pattern must be consistent with the diagnosis of IS (hypsarrhythmia, modified hypsarrhythmia, multifocal spike wave discharges, etc).
- •Have a vEEG recording confirming the diagnosis of IS.
- •Have had a magnetic resonance imaging (MRI) performed to determine any possible causes of IS.
- •Have been previously treated with 3 or fewer AEDs.
- •If being treated with concomitant AEDs
- •Current AEDs have been at a constant daily dose for at least 2 weeks; Note: Subjects with minor dose adjustments may be allowed to enter the study after shorter periods after detailed discussion with the medical monitor.
- •Have a stable clinical response/plateau for at least 2 weeks
- •Are able to continue treatment with no more than 2 concomitant AEDs (ACTH, corticosteroids, felbamate, and vigabatrin are not allowed concomitantly).
- •A ketogenic diet is permitted if it can be maintained for the duration of the study.
- •Be a male or female, 4 to 24 months of age (inclusive)
- •Have a Parent/Guardian who is properly informed of the nature and risks of the clinical study, who is willing and capable of complying with all clinical study procedures, and has given informed consent in writing prior to entering the clinical study
- •Be able to participate for the full term of the clinical study.
排除标准
- •Treatment with corticosteroids, ACTH, vigabatrin, felbamate, or any AED not approved by Regulatory Agencies, 2 weeks prior to randomization.
- •Treatment with more than two AEDs at baseline.
- •Have an active CNS infection, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive (with the exception of tuberous sclerosis) as evaluated by brain imaging (MRI).
- •Have any disease or condition (medical or surgical) at screening that might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, or hepatic systems; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the investigational product, or would place the subject at increased risk.
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin greater than four times the upper limit of normal (ULN) or clinical laboratory value deemed clinically significant by the Investigator.
- •History of recurrent status epilepticus.
- •Have been exposed to any other investigational drug within 30 days prior to randomization.
研究组 & 干预措施
ganaxolone
ganaxolone
干预措施: Ganaxolone (Drug)
non-active drug
placebo
干预措施: Placebo (Other)
结局指标
主要结局
Change From Baseline in Frequency of Spasm Clusters at Day 10
时间窗: Baseline (Day 0) and Day 10
Spasm clusters were determined by a 24-hour video-electroencephalography (vEEG) at Day 10. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the Day 0 assessment before study drug infusion.
次要结局
- Number of Participants With Seizure-free Days(From Day 8 to Day 10 and From Day 18 to Day 20)
- Number of Responders(Day 10 and Day 20)
- Change From Baseline in Frequency of Spasm Clusters at Day 20(Baseline (Day 0) and Day 20)
- Number of Participants With Change in Clinical Status on Caregiver's Global Assessment(Baseline (Day 0), Day10 and Day 20)
- Number of Participants With Absence of Hypsarrhythmia(Day 10 and Day 20)
- Number of Participants With Change in Clinical Status on the Investigator's Global Assessment(Baseline (Day 0), Day 10 and Day 20)
- Number of Participants With Spasm-free Durations(Day 10 and Day 20)
- Developmental Assessment Using Denver-II Developmental Test at Day 20(At Day 20)