A Phase 1b Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION356 in Patients With Pelizaeus Merzbacher Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of Participants With Clinically Significant Change From Baseline in Electrocardiography (ECG)
研究概览
简要总结
The primary purpose of this study is to evaluate the safety and tolerability of ION356.
详细描述
This is a Phase 1b, open-label multiple-ascending dose (MAD) study of ION356 in approximately 24 pediatric participants with Pelizaeus-Merzbacher Disease and genetic confirmation of proteolipid protein 1 (PLP1) gene duplication. The study will have 2 parts: a 48-week multiple-ascending dose (MAD) part followed by a long-term extension (LTE) part of 109 weeks. Eligible participants will receive doses of ION356 during the MAD portion of the study and upon completion will seamlessly transition to the open-label LTE to receive doses of ION356.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 17 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort A: ION356 Dose A
Participants will receive ION356 intrathecally at Dose A in the MAD Period, followed by ION356 Dose A in the LTE Period.
干预措施: ION356 (Drug)
Cohort B: ION356 Dose B
Participants will receive ION356 intrathecally at Dose B in the MAD Period, followed by ION356 Dose B in the LTE Period.
干预措施: ION356 (Drug)
结局指标
主要结局
Number of Participants With Clinically Significant Change From Baseline in Electrocardiography (ECG)
时间窗: Baseline up to Week 145
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
时间窗: Up to Week 145
Number of Participants With Change From Baseline in Concomitant Medication Use
时间窗: Baseline up to Week 145
Number of Participants With Clinically Significant Change from Baseline in Laboratory Assessments
时间窗: Baseline up to Week 145
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
时间窗: Baseline up to Week 145
Number of Participants With Clinically Significant Change From Baseline in Neurological Examination Findings
时间窗: Baseline up to Week 145
次要结局
- Maximum Plasma Concentration (Cmax) of ION356(Pre-dose and at multiple points post-dose up to Week 145)
- Cerebrospinal Fluid (CSF) Concentration of ION356(Pre-dose and at multiple points post-dose up to Week 105)
- Plasma Concentration of ION356(Pre-dose and at multiple points post-dose up to Week 145)
- Area Under the Concentration-time Curve (AUC) of ION356(Pre-dose and at multiple points post-dose up to Week 145)
- Plasma Terminal Elimination Half-life (t½) of ION356(Pre-dose and at multiple points post-dose up to Week 145)
- Concentration of ION356 Excreted in Urine(Pre-dose and at multiple points post-dose on Week 1 and Week 49)
- Percent of ION356 Dose Excreted in Urine(Pre-dose and at multiple points post-dose on Week 1 and Week 49)
- Renal Clearance of ION356(Pre-dose and at multiple points post-dose on Week 1 and Week 49)