A Phase 2,Double-Blind,Randomized Clinical Trial to Explore the Safety,Tolerability,Efficacy, and Pharmacokinetics of PRAX-562 in Pediatric Participants With Developmental and Epileptic Encephalopathies Followed by Open-Label Extension(OLE)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 77
- 试验地点
- 8
- 主要终点
- PART A (Cohorts 1 and 2) RDB: To evaluate the safety and tolerability of PRAX 562 in pediatric participants with SCN2A- and SCN8A- DEEs
研究概览
简要总结
A Clinical Trial of PRAX-562 in Subjects With Developmental and Epileptic Encephalopathies (DEE)
详细描述
A Phase 2, double-blind, randomized clinical trial to evaluate the safety and tolerability of PRAX 562 in pediatric participants with SCN2A- and SCN8A- DEEs.
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)
盲法说明
Double-blind
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a documented variant in SCN2A with onset of seizures occurring in the first 3 months of life or has a diagnosis of SCN8A-DEE supported by both clinical and genetic findings.
- •Has a seizure frequency as follows:
- •At least 8 countable motor seizures in the 4 weeks immediately prior to Screening as reported by the parent/legal guardian or in the opinion of the investigator as documented in medical notes.
- •AND o At least 8 countable motor seizures during the 28 day Baseline Observation Period (during which seizure frequency is recorded in a daily seizure diary).
- •Additional inclusion criteria apply and will be assessed by the study team.
排除标准
- •Has any clinically significant or known pathogenic or likely pathogenic genetic variant other than in SCN2A and SCN8A or a genetic variant that may explain or contribute to the participant's epilepsy and/or developmental disorder.
- •Has a documented, functionally characterized loss-of-function (LoF) missense variant or a presumed LoF variant (nonsense or frameshift variant) based on genetic testing and/or clinical evidence that prior exposure to a sodium channel blocker (SCB) medication worsened seizures.
- •Has 2 or more episodes of convulsive status epilepticus requiring hospitalization and intubation in the 6 months prior to Screening.
- •Additional exclusion criteria apply and will be assessed by the study team.
研究组 & 干预措施
Part A: Randomized, Double-Blind 0.5mg/kg/day PRAX-562 or PRAX-562/Placebo
Eligible participants from each cohort will be randomized in a 1:1 ratio to either 0.5 milligrams/kilograms/day (mg/kg/day) PRAX-562 for 16 weeks (PRAX-562 arm) or 0.5 mg/kg/day PRAX-562 for 12 weeks and matching placebo for 4 weeks (PRAX-562/placebo arm) administered orally or via gastrostomy tube (G-tube).
干预措施: PRAX-562 (Drug)
Part B: Open-Label Extension Treatment 0.5mg/kg/day PRAX-562
Eligible participants will receive 0.5mg/kg/day administered orally or via G-tube for up to 144 weeks.
干预措施: PRAX-562 (Drug)
Part A: Randomized, Double-Blind 1.0 mg/kg/day PRAX-562 or PRAX-562/Placebo
Eligible participants from each cohort will be randomized in a 1:1 ratio to either 1.0 milligrams/kilograms/day (mg/kg/day) PRAX-562 for 16 weeks (PRAX-562 arm) or 1.0 mg/kg/day PRAX-562 for 12 weeks and matching placebo for 4 weeks (PRAX-562/placebo arm) administered orally or via gastrostomy tube (G-tube).
干预措施: PRAX-562 (Drug)
Open-Label Extension Treatment 1.0 mg/kg/day PRAX-562
Eligible participants will receive 1.0 mg/kg/day administered orally or via G-tube for up to 144 weeks.
干预措施: PRAX-562 (Drug)
结局指标
主要结局
PART A (Cohorts 1 and 2) RDB: To evaluate the safety and tolerability of PRAX 562 in pediatric participants with SCN2A- and SCN8A- DEEs
时间窗: 16 weeks
Changes from baseline in monthly (28-day) motor seizure frequency
PART B (Cohorts 1 and 2) OLE: To evaluate the long-term safety and tolerability of PRAX-562 in pediatric participants with DEEs
时间窗: 48 weeks
Incidence and severity of TEAEs
次要结局
- Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability])(16 weeks)
- Plasma concentrations of PRAX-562(16 weeks)
- Seizure Frequency (OLE Extension)(48 weeks)
- PART A (Cohorts 1 and 2) RDB: To assess the effect of PRAX-562 on the frequency of countable motor seizures in pediatric participants with DEEs(16 weeks)
- To assess the effect of PRAX-562 on the frequency of countable motor seizures in pediatric participants with DEEs(16 weeks)