A 20-Week Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of EPX-100 (Clemizole Hydrochloride) as Adjunctive Therapy in Children and Adult Participants With Dravet Syndrome (ARGUS Trial)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 113
- 主要终点
- Percent Change in Countable Motor Seizures Per 28 Days (CMS-28) in the Titration Plus Maintenance Periods Relative to Baseline
研究概览
简要总结
This is a multicenter, Phase 3, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of clemizole hydrochloride (EPX-100) as adjunctive therapy in children and adult participants with Dravet syndrome (DS).
详细描述
This is a global, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of clemizole hydrochloride as adjunctive therapy in children and adult participants with DS. The study consists of a 4-week Observational Period, a 16-week Double-Blind (DB) Period and an Open-Label Extension (OLE) Period.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female participants 2 years and older at time of consent.
- •Participant or parent/legally authorized representative (LAR) willing and able to provide written informed consent and assent (if applicable) prior to initiation of any study related procedures.
- •Clinical diagnosis of DS. Participants must have seizures which are not completely controlled by AEDs with the following criteria:
- •Onset of seizures prior to 18 months of age,
- •Normal development at onset,
- •History of at least one type of countable motor seizure (CMS),
- •Brain MRI without cortical malformation (not including mild atrophy associated with the natural progression of DS),
- •Genetic mutation of the SCN1A gene must be documented.
排除标准
- •Known sensitivity, allergy, or previous exposure to clemizole HCl.
- •Exposure to any investigational drug or device <90 days prior to screening or plans to participate in another drug or device trial at any time during the study.
- •Seizures secondary to illicit drug (this includes concomitant use of tetrahydrocannabinol [THC] and nonprescription cannabidiol preparations) or alcohol use, infection, neoplasm, demyelinating disease, degenerative neurological disease, or central nervous system disease deemed progressive, metabolic illness, or progressive degenerative disease.
- •Concurrent use of lorcaserin. Note: Prior use of lorcaserin is permitted if at least 30 days have passed since the last dose.
- •Concurrent use of fenfluramine.
- •Epilepsy surgery planned during the study or epilepsy surgery within 6 months prior to Screening.
研究组 & 干预措施
Double-blind clemizole HCl
Participants will receive their first dose of study drug following randomization.
干预措施: Clemizole HCl (Drug)
Open-label clemizole HCl
Eligible participants who complete the DB Period will have the option to continue in the OLE Period, during which they will receive clemizole HCL for up to 3 years.
干预措施: Clemizole HCl (Drug)
Placebo
Participants will receive their first dose of study drug following randomization.
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Change in Countable Motor Seizures Per 28 Days (CMS-28) in the Titration Plus Maintenance Periods Relative to Baseline
时间窗: From Baseline Period (Day 1) up to 16 weeks
Percent change in CMS-28 from the Baseline Period through the end of the DB period.
European Union: Percent Change in Countable Motor Seizures Per 28 Days in the Maintenance Period Relative to Baseline
时间窗: From maintenance period Baseline (Day 29) up to Day 85
Percent change in CMS-28 from the Baseline Period through the end of the maintenance period.
次要结局
- Incidence of Treatment-Emergent Adverse Events (TEAEs)(From the first dose administration of study drug up to end of the study, approximately up to 172 weeks)
- Proportion of Participants with >=50% reduction in Countable Motor Seizures Per 28 Days in the Titration Plus Maintenance Periods Relative to Baseline(From Baseline Period (Day 1) up to 16 weeks)
- European Union: Proportion of Participants with >=50% reduction in Countable Motor Seizures Per 28 Days in the Maintenance Period Relative to Baseline(From maintenance period Baseline (Day 29) up to Day 85)
- Number of Countable Motor Seizure-free Days in the Titration Plus Maintenance Periods Relative to Baseline(From Baseline Period (Day 1) up to 16 weeks)
- European Union: Number of Countable Motor Seizure-free Days in the Maintenance Period Relative to Baseline(From maintenance period Baseline (Day 29) up to Day 85)
- Clinical Global Impression of Improvement - Clinician (CGII-C) Score(Day 85)
- Clinical Global Impression of Improvement - Participant/Caregiver (CGII-P) Score(Day 85)
- Percent Change in All Seizures in the Titration Plus Maintenance Periods Relative to Baseline(From Baseline Period (Day 1) up to 16 weeks)
- Percent Change in All Seizures in the Maintenance Period Relative to Baseline(From maintenance period Baseline (Day 29) up to Day 85)
- Incidence of Rescue Anti-epileptic Drug (AED) Use in the Titration Plus Maintenance Periods Relative to Baseline(From Baseline Period (Day 1) up to 16 weeks)
- Incidence of Rescue Anti-epileptic Drug Use in the Maintenance Period Relative to Baseline(From maintenance period Baseline (Day 29) up to Day 85)
- United States FDA: Proportion of Participants with >=50% Reduction in the Countable Motor Seizures Per 28 Days in the Maintenance Period Relative to Baseline(From maintenance period Baseline (Day 29) up to Day 85)
- Incidence of Treatment-Emergent Adverse Events (TEAEs)(From the first dose administration of study drug up to end of the study, approximately up to 172 weeks)