An Open-Label Extension Study for Patients With Dravet Syndrome Who Previously Participated in Studies of STK-001
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 60
- 试验地点
- 20
- 主要终点
- Safety of multiple doses of zorevunersen
研究概览
简要总结
Stoke Therapeutics is evaluating the long-term safety & tolerability of repeated doses of zorevunersen (STK-001) in patients with Dravet syndrome who previously participated in studies of zorevunersen. Change in seizure frequency and overall clinical status, and quality of life will be measured as secondary endpoints in this open-label study.
详细描述
This study is a multi-center, open-label, multiple-dose, safety extension study for patients who have completed another study of zorevunersen and meet study eligibility criteria. zorevunersen is an investigational new medicine for the treatment of Dravet syndrome. Zorevunersen is an antisense oligonucleotide (ASO) that is intended to increase the level of productive SCN1A messenger RNA (mRNA) and consequently increase the expression of the sodium channel Nav1.1 protein. This RNA-based approach is not gene therapy, but rather RNA modulation, as it does not manipulate nor insert genetic deoxyribonucleic acid (DNA).
Zorevunersen is designed to upregulate Nav1.1 protein expression from the nonmutant (wild-type) copy of the SCN1A gene to restore physiological Nav1.1 levels. Nav1.1 levels are reduced in people with Dravet syndrome. Stoke has generated preclinical data demonstrating proof-of-mechanism for zorevunersen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Completed dosing with zorevunersen and the End of Study Visit in Study STK-001-DS-101 or Study STK-001-DS-102, with an acceptable safety profile per Investigator judgment.
- •Had satisfactory compliance with study visits and procedures in Study STK-001-DS-101 or Study STK-001-DS-102 per Investigator and Sponsor judgment.
- •Completed Study STK-001-DS-101 or STK-001-DS-102 within 4 weeks of the start of their participation in Study STK-001-DS-501 unless approved by sponsor.
排除标准
- •Met any withdrawal criteria from Study STK-001-DS-101 or STK-001-DS-
- •Currently treated with an antiepileptic drug (AED) acting primarily as a sodium channel blocker, as maintenance therapy, including phenytoin, carbamazepine, oxcarbazepine, lamotrigine, lacosamide or rufinamide (with the exception of cenobamate, which is permitted).
- •Clinically significant unstable medical conditions other than epilepsy.
- •Clinically relevant symptoms or a clinically significant illness (in the judgment of the Investigator) at Screening or prior to dosing on Day 1, other than epilepsy.
- •Spinal deformity or other condition that may alter the free flow of CSF or has an implanted CSF drainage shunt.
- •Treated (or is being treated) with an investigational product (other than zorevunersen) since participating in Study STK-001-DS-101 or STK-001-DS-
- •Participating in an observational study, they are excluded unless approved by the Sponsor.
研究组 & 干预措施
zorevunersen (STK-001) multiple dose levels
Enrollment of patients after completion of Study STK-001-DS-101 or Study STK-001-DS-102 if eligible. Patients will receive IT administration of study drug zorevunersen at the dose level they received while participating in Study STK-001-DS-101 or STK-001-DS-102, or at a dose level recommended by the Safety Monitoring Committee (SMC).The highest dose administered in this study may not exceed that which has already been evaluated in an zorevunersen Phase 1/2 study, and doses above 45 mg/dose in this study require approval from the Food and Drug Administration (FDA). Patients will initially receive 3 doses, one every approximately 4 months (16 weeks). Patients who are tolerating treatment may continue treatment with doses approximately every 4 months, with an End of Study/Follow-up Visit 24 weeks after the last dose of study drug. Patients who do not continue treatment after the third dose will have a Follow-up Visit (V5) at Week 48 and an End of Study Visit at Week 56.
干预措施: zorevunersen (STK-001) (Drug)
结局指标
主要结局
Safety of multiple doses of zorevunersen
时间窗: Screening (Day -1) until 6 months after multiple drug dosing
Safety variables for analysis include the incidence, type, severity, and seriousness of AEs, and changes in vital signs, ECG, laboratory, immunogenicity, physical examination, and outcomes on the cerebellar function clinical screening battery.
次要结局
- Measurement of Seizure Frequency(Screening (Day -1) until 6 months after multiple drug dosing)
- Change in Quality of Life(Screening (Day -1) until 6 months after multiple drug dosing)
- Change in overall clinical status(Screening (Day -1) until 6 months after multiple drug dosing)
- Pharmacokinetic (PK) Parameters(Dosing (Day 1) until 6 months after multiple drug dosing)
- Exposure of zorevunersen in Cerebrospinal Fluid (CSF)(Dosing (Day 1) and every 4 months until last study drug dosing day)