A Seamless, Clinical Trial to Investigate the Safety and Efficacy of Multiple Doses of PRAX-222 in Pediatric Participants With Early Onset SCN2A Developmental and Epileptic Encephalopathy
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 60
- 试验地点
- 6
- 主要终点
- Seizure frequency (Confirmatory Phase)
研究概览
简要总结
The goal of this trial is to learn about the effect of PRAX-222 in pediatric participants with early onset SCN2A developmental and epileptic encephalopathy (DEE), aged 2 to 18 years.
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)
盲法说明
No masking in the 2 open-label parts, masking as indicated in the 2 double-blind, randomized parts.
入排标准
- 年龄范围
- 2 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has onset of seizures prior to 3 months of age.
- •Has a minimum weight of at least 10 kg at screening.
- •Has a documented SCN2A variant through genetic testing obtained via a laboratory accredited per Clinical Laboratory Improvement Amendments (CLIA) or College of American Pathologists (CAP) or equivalent.
- •Additional inclusion criteria apply and will be assessed by the study team
排除标准
- •Has any clinically significant or known pathogenic genetic variant other than in the SCN2A gene, or a genetic variant that may explain or contribute to the participant's epilepsy and/or developmental disorder.
- •Is taking more than 2 sodium channel blocking anti-seizure medications
- •Additional exclusion criteria apply and will be assessed by the study team
研究组 & 干预措施
Optional Dose Escalation - PRAX-222
Optional dose escalation consisting of double-blind ascending doses of PRAX-222
干预措施: PRAX-222 - Optional Ascending Doses (Drug)
Confirmatory Dosing - PRAX-222
Double-blind fixed-dose PRAX-222
干预措施: PRAX-222 - Fixed Doses (Drug)
Confirmatory Dosing - Placebo
Double-blind placebo procedure
干预措施: Placebo (Procedure)
Open-label PRAX-222
Open-label PRAX-222
干预措施: PRAX-222 - Fixed Doses (Drug)
Optional Dose Escalation - Placebo
Double-blind placebo procedure
干预措施: Placebo (Procedure)
Dose Escalation - PRAX-222
Initial dose escalation consisting of double-blind ascending doses of PRAX-222
干预措施: PRAX-222 - Initial Ascending Doses (Drug)
Preliminary Safety
Open-label PRAX-222
干预措施: PRAX-222 - Initial Dose (Drug)
Dose Escalation - Placebo
Double-blind placebo procedure
干预措施: Placebo (Procedure)
结局指标
主要结局
Seizure frequency (Confirmatory Phase)
时间窗: 36 to 40 weeks
Seizure frequency will be captured by a seizure diary and outcomes will be measured by summing the seizure frequency over a 28-day time period following the 6th dose administration in the confirmatory phase.
Number of participants with treatment-emergent adverse events (Preliminary Safety, Dose Escalation)
时间窗: Screening (-8 weeks) through up to 92 weeks
The number of participants with treatment-emergent adverse events will be reported by severity and preferred term.
次要结局
- Seizure frequency (Preliminary Safety)(0 to 4 weeks, 4 to 8 weeks, 8 to 12 weeks)
- Percent change in seizure frequency (Preliminary Safety)(0 to 4 weeks, 4 to 8 weeks, 8 to 12 weeks)
- Seizure frequency (Dose Escalation Phase)(0 to 4 weeks, 4 to 8 weeks, 8 to 12 weeks, 12 to 16 weeks, 18 to 22 weeks, 30 to 34 weeks (Group 1, optional), 36 to 40 weeks (Group 1, optional), 42 to 46 weeks (Group 1, optional), 48 to 52 weeks (Group 1, optional), 54 to 58 weeks (Group 1, optional))
- Seizure frequency (Confirmatory Phase)(0 to 4 weeks, 6 to 10 weeks, 12 to 16 weeks, 18 to 22 weeks, 24 to 28 weeks)
- Percent change in seizure frequency (Dose Escalation Phase)(0 to 4 weeks, 4 to 8 weeks, 8 to 12 weeks, 12 to 16 weeks, 18 to 22 weeks, 30 to 34 weeks (optional), 36 to 40 weeks (optional), 42 to 46 weeks (optional), 48 to 52 weeks (optional), 54 to 58 weeks (optional))
- Percent change in seizure frequency (Confirmatory Phase)(0 to 4 weeks, 6 to 10 weeks, 12 to 16 weeks, 18 to 22 weeks, 24 to 28 weeks)
- Number of participants with a treatment response (Confirmatory Phase)(0 to 4 weeks, 6 to 10 weeks, 12 to 16 weeks, 18 to 22 weeks, 24 to 28 weeks)
- Change from baseline in Clinical Global Impression-Severity (CGI-S) score (Confirmatory Phase)(6 weeks, 12 weeks, 18 weeks, 24 weeks, 36 weeks, 60 weeks)
- Number of participants with a treatment response (Preliminary Safety)(0 to 4 weeks, 4 to 8 weeks, 8 to 12 weeks)
- Number of participants with a treatment response (Dose Escalation Phase)(0 to 4 weeks, 4 to 8 weeks, 8 to 12 weeks, 12 to 16 weeks, 18 to 22 weeks, 30 to 34 weeks (optional), 36 to 40 weeks (optional), 42 to 46 weeks (optional), 48 to 52 weeks (optional), 54 to 58 weeks (optional))
- Change from baseline in Caregiver Global Impression-Severity (CgGI-S) score (Confirmatory Phase)(6 weeks, 12 weeks, 18 weeks, 24 weeks, 36 weeks, 60 weeks)
- Clinical Global Impression-Improvement (CGI-I) score (Confirmatory Phase)(6 weeks, 12 weeks, 18 weeks, 24 weeks, 36 weeks, 60 weeks)
- Changes in EEG-based outcome measures (Confirmatory Phase)(Week 2, Week 42)
- Caregiver Global Impression-Improvement (CgGI-I) score (Confirmatory Phase)(6 weeks, 12 weeks, 18 weeks, 24 weeks, 36 weeks, 60 weeks)
- Quality of life as assessed by Quality of Life Inventory-Disability (Confirmatory Phase)(36 weeks)
- Behavior as assessed by Vineland Adaptive Behavior Scale-3rd edition (Vineland-3; Confirmatory Phase)(36 weeks)
- Developmental milestones (Confirmatory Phase)(36 weeks)
- Behavior as assessed by Aberrant Behaviors Checklist-2nd edition (ABC-2; Confirmatory Phase)(36 weeks)
- Sleep as assessed by Sleep Disturbance Scale for Children (Confirmatory Phase)(36 weeks)
- Seizure frequency (Preliminary Safety)(12 to 16 weeks)
- Seizure frequency (Dose Escalation Phase)(24 to 28 weeks (Group 1), 30 to 34 weeks (Group 2, optional))