Phase 1-2, Open-Label, Single and Multiple Ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally-Administered ION337 in Patients With Dravet Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 32
- 试验地点
- 6
- 主要终点
- Parts 1 and 2: Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examination Findings
研究概览
简要总结
The primary purpose of this study is to evaluate the safety and tolerability of ION337 in participants with Dravet syndrome (DS).
详细描述
This is an open-label study of ION337 in people with DS between the ages of 2 and 12 years old (inclusive). The study consists of 2 parts: Part 1) 6-month single ascending dose (SAD) and Part 2) 24-month multiple ascending dose (MAD), followed by a 7-month safety follow up.
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
- 2 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant is aged ≥ 2 to ≤ 12 years old at the time of informed consent.
- •Participant has at least 1 parent or caregiver ≥ 18 years old who is willing and able to provide informed consent (signed and dated) and attend all scheduled study visits.
- •Has a documented diagnosis of DS according to the International League Against Epilepsy (ILAE) criteria and as agreed by the Epilepsy Study Consortium, Inc (ESCI).
- •Has confirmation of a pathogenic or likely pathogenic SCN1A variant.
- •Must be currently receiving ≥ 1 concomitant ASM at a stable dose/regimen for ≥ 4 weeks prior to informed consent.
- •Must have all other interventions for epilepsy (including ketogenic diet or VNS) as well as any other concomitant medications including medications for behavioral management, sleep, and supplements or nutritional support stable for ≥ 4 weeks prior to informed consent. Vagus nerve stimulator implantation must have occurred ≥ 6 months prior to informed consent.
- •Experiences the required number of major motor seizures during the Screening Period.
排除标准
- •Known brain or spinal disease that would interfere with the LP procedure or CSF circulation, or presence of other factors that would affect the safety of the LP procedure.
- •Pathogenic or likely pathogenic variant in another gene that causes epilepsy.
- •Has had prior treatment with or is currently enrolled in an interventional clinical trial for a gene therapy or for another antisense oligonucleotide (ASO) for the treatment of DS.
- •Has had treatment with or is currently enrolled in an interventional clinical trial of any other investigational drug, biological agent, or device within 30 days prior to Screening, or 5 half-lives of investigational agent, whichever is longer.
- •Current treatment with an anti-seizure medication (ASM) acting primarily as a sodium channel blocker, as maintenance treatment.
- •Prior brain surgeries including: corpus callosotomy, implantation of device for deep brain stimulation or any other palliative brain surgery intended to reduce seizure burden.
- •Note: Other protocol pre-specified inclusion/exclusion criteria may apply.
研究组 & 干预措施
Part 1: SAD: Dose Level 2
Participants aged 2 to ≤ 12 will receive a single dose of ION337.
干预措施: ION337 (Drug)
Part 1: SAD: Dose Level 4
Participants aged 2 to ≤ 12 will receive a single dose of ION337.
干预措施: ION337 (Drug)
Part 2: Multiple Ascending Dose (MAD): Dose Level 1-4
Only participants who complete Part 1 will be eligible to participate in Part 2. Participants will receive multiple doses of ION337. Participants will begin treatment at the same dose level assigned in Part 1.
干预措施: ION337 (Drug)
Part 1: Single Ascending Dose (SAD): Dose Level 1
Participants aged 2 to ≤ 12 years will receive a single intrathecal bolus (ITB) injection of ION337.
干预措施: ION337 (Drug)
Part 1: SAD: Dose Level 3
Participants aged 2 to ≤ 12 will receive a single dose of ION337.
干预措施: ION337 (Drug)
结局指标
主要结局
Parts 1 and 2: Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examination Findings
时间窗: Part 1: up to 6 months; Part 2: up to 31 months
Parts 1 and 2: Number of Participants with Change in Columbia Suicidality Severity Rating Scale (C-SSRS)
时间窗: Part 1: up to 6 months; Part 2: up to 31 months
Parts 1 and 2: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
时间窗: Part 1: up to 6 months; Part 2: up to 31 months
Parts 1 and 2: Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG)
时间窗: Part 1: up to 6 months; Part 2: up to 31 months
Parts 1 and 2: Number of Participants with Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
时间窗: Part 1: up to 6 months; Part 2: up to 31 months
Number of Participants With Clinically Significant Change From Baseline in Safety Laboratory Values
时间窗: Part 1: up to 6 months; Part 2: up to 31 months
次要结局
- Pharmacokinetic (PK) Parameters Measure Description: Analysis of plasma concentrations of ION337(Pre-Dose Day 1 (Dosing) until 6 months after dosing in Part 1 and up to 31 months in Part 2)
- Exposure of ION337 in Cerebrospinal Fluid (CSF) Measure Description: Measurement of ION337 concentrations(Pre-dose Day 1 (Dosing) until 6 months after dosing in Part 1 and up to 31 months in Part 2)
- Parts 1 and 2: Percent Change From Baseline in 28-day Normalized Major Motor Seizure (MMS) Frequency(Part 1: up to 6 months; Part 2: up to 31 months)