EXPEDITION: A Clinical Study to Evaluate the Safety and Efficacy of ETX101, an AAV9-Delivered Gene Therapy in Children With SCN1A-positive Dravet Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 5
- 试验地点
- 6
- 主要终点
- Proportions of participants experiencing any treatment-emergent adverse events (AEs), serious adverse events (SAEs), related AEs, AEs with severity Grade ≥ 3, AEs resulting in study discontinuation, and AEs with fatal outcome.
研究概览
简要总结
EXPEDITION is a Phase 1/2 study in the UK to evaluate the safety and efficacy of ETX101 in participants with SCN1A-positive Dravet Syndrome aged 6 to < 48 months. The study follows and open-label, dose-escalation design.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 47 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant has a predicted loss of function pathogenic or likely pathogenic SCN1A variant
- •Participant must have experienced their first seizure between the age of 3 and 15 months
- •Participant must have a clinical diagnosis of Dravet syndrome or the treating clinician must have 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 is currently taking or has taken antiseizure medications (ASMs) at a therapeutic dose that are contraindicated in Dravet syndrome, including sodium channel blockers.
- •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
Cohort A
Cohort A will evaluate ETX101 dose level 1.
干预措施: ETX101 (Drug)
Cohort B
Cohort B will evaluate ETX101 dose level 2.
干预措施: ETX101 (Drug)
Cohort C
Cohort C will evaluate ETX101 dose level 3.
干预措施: ETX101 (Drug)
Cohort D
Cohort D will evaluate ETX101 dose level 4.
干预措施: ETX101 (Drug)
结局指标
主要结局
Proportions of participants experiencing any treatment-emergent adverse events (AEs), serious adverse events (SAEs), related AEs, AEs with severity Grade ≥ 3, AEs resulting in study discontinuation, and AEs with fatal outcome.
时间窗: Day 1 through Study Completion, an average of 5 years
Change from baseline in the standard score of the Vineland Adaptive Behavior Scales - Third Edition Adaptive Behavior Composite at Week 52.
时间窗: Baseline to Week 52. Standard scores are normalized to a mean and SD of 100 and 15, respectively, and are not bounded by a range. Higher scores correspond to better outcomes.
次要结局
- Percent change in monthly countable seizure frequency (MCSF) to Week 52, with countable seizures defined as generalized tonic-clonic/clonic, focal motor with clearly observable clinical signs, tonic bilateral, and atonic seizures.(Between the 8-week baseline period and the 48-week post-dosing assessment period (defined as Week 5 to Week 52 following administration of ETX101))
- Change from baseline in the raw score of the Bayley Scales of Infant and Toddler Development® 4th Edition receptive language sub-domain at Week 52.(Baseline to Week 52. Raw scores range from 0 to 49 and higher scores correspond to better outcomes.)