ENDEAVOR: A Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Infants and Children With SCN1A-Positive Dravet Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 47
- 试验地点
- 15
- 主要终点
- Percent change in monthly countable seizure frequency (MCSF) between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period.
研究概览
简要总结
ENDEAVOR is a Phase 1/2, 2-part, multicenter study to evaluate the safety and efficacy of ETX101 in participants with SCN1A-positive Dravet syndrome aged ≥6 to <36 months (Part 1A), aged ≥48 months to <18 years (Part 1B), and aged ≥6 to <48 months (Part 2). Part 1A follows an open-label, dose-escalation design, Part 1B follows an open-label design, and Part 2 is a randomized, double-blind, sham delayed-treatment control study.
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
Part 1A and Part 1B are open-label with no blinding.
Part 2 will be conducted in a double-blinded manner whereby all Primary Site Staff (including clinicians, research coordinators, neuropsychologists, pharmacists, and physical therapists), study participants and caregivers, Sponsor and Sponsor-designees will be blinded through the end of Week 52 following Day 1 for each participant. The Surgical Site Staff will be unblinded to treatment assignment.
入排标准
- 年龄范围
- 6 Months 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be aged between ≥6 months and <36 months in Part 1A, ≥48 months and <18 years in Part 1B, ≥6 months and <48 months in Part
- •Participant must have a predicted loss of function pathogenic or likely pathogenic SCN1A variant.
- •Participant must have experienced their first seizure between the ages of 3 and 15 months.
- •Participant must have a clinical diagnosis of Dravet syndrome or the treating clinician must have a high clinical suspicion of a diagnosis of Dravet syndrome.
- •Participant is receiving at least one prophylactic antiseizure medication.
排除标准
- •Participant has another genetic mutation or clinical comorbidity which could potentially confound the typical Dravet phenotype.
- •Participant has a known central nervous system structural and/or vascular abnormality (indicated by an MRI or CT scan of the brain).
- •Participant has an abnormality that may interfere with CSF distribution and/or has an existing ventriculoperitoneal shunt.
- •Participant has received sodium channel blockers during the Pre-Dosing Seizure Period.
- •Participant has experienced seizure freedom for a period of 4 consecutive weeks within the 90-day period prior to informed consent.
- •Participant has previously received gene or cell therapy.
- •Participant is currently enrolled in a clinical trial or receiving an investigational therapy.
- •Participant has clinically significant underlying liver disease.
研究组 & 干预措施
Part 2
Part 2 will follow a double-blind (up through Week 52), randomized, sham delayed-treatment control design.
There will be 2 cohorts in Part 2. A single dose level of ETX101 will be evaluated in Part 2 and participants will be randomized 2:1 to study treatment or sham procedure with delayed treatment.
干预措施: ETX101 (Drug)
Part 1 (US Only)
Part 1A will follow an open-label, rule-based, dose-escalation design and will evaluate up to 4 dose levels of ETX101. Part 1B will follow an open-label design and will evaluate 1 dose level of ETX101.
干预措施: ETX101 (Drug)
结局指标
主要结局
Percent change in monthly countable seizure frequency (MCSF) between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period.
时间窗: Between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period (defined as Week 5 to Week 52).
次要结局
- Change from Baseline in Bayley-4 cognitive subdomain raw score at Week 52 (Key Secondary Endpoint for Part 2).(From Baseline to Week 52.)
- Change from Baseline in Vineland-3 subdomain GSVs at Week 52.(From Baseline to Week 52.)
- Change from Baseline in Bayley-4 subdomain GSVs at Week 52.(From Baseline to Week 52.)
- Proportion of participants achieving ≥ 75% reduction in MCSF between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period.(Between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period (defined as Week 5 to Week 52).)
- Proportion of participants achieving ≥ 50% reduction in MCSF between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period.(Between the Pre-Dosing Seizure Period and the Post-Dosing Assessment Period (defined as Week 5 to Week 52).)
- Change from Baseline in the Vineland-3 Adaptive Behavior Composite standard score at Week 52.(From Baseline to Week 52.)
- Change from Baseline in Vineland-3 subdomain raw scores at Week 52.(From Baseline to Week 52.)
- Change from Baseline in Bayley-4 subdomain raw scores (excluding cognitive subdomain) at Week 52.(From Baseline to Week 52.)
- Proportion of CGI-I responders, defined as participants with a CGI-I score of 1 (Very much improved) or 2 (Much improved), at Week 52.(From Baseline to Week 52.)
- Proportion of CGI-S responders, defined as participants who either have a CGI-S score of 1 (Normal, not at all ill) or demonstrate a ≥2 point improvement from Baseline, at Week 52.(From Baseline to Week 52.)