A Multicenter, Randomized, Double-blind, Placebo Controlled, Phase 1b/2a Study of WVE-003 Administered Intrathecally in Patients With Huntington's Disease (SELECT-HD)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 23
- 主要终点
- Safety: Proportion of Patients With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug
研究概览
简要总结
This is a Phase 1b/2a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of WVE-003 in adult patients with early-manifest HD who carry the targeted single nucleotide polymorphism (SNP) - SNP3.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 25 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Presence of the A variant of SNP3 on the same allele as the pathogenic CAG triplet expansion
- •Ambulatory, male or female patients aged ≥25 to ≤60 years
- •Clinical diagnostic motor features of HD, defined as Unified Huntington's Disease Rating Scale (UHDRS) Diagnostic Confidence Score = 4
- •UHDRS Total Functional Capacity Scores ≥9 and ≤13
排除标准
- •Malignancy or received treatment for malignancy, other than treated basal cell or squamous cell carcinoma of the skin, within the previous 5 years
- •Received any other study drug, including an investigational oligonucleotide, within the past 1 year or 5 half-lives of the drug, whichever is longer, with the exception of the following:
- •a. Received WVE-120101 or WVE-120102 within the last 3 months
- •Implantable CNS device that may interfere with ability to administer study drug via lumbar puncture or undergo MRI scan
- •Inability to undergo brain MRI (with or without sedation)
- •Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or unsuccessful lumbar puncture
- •Previously received tominersen
研究组 & 干预措施
SAD: Pooled Placebo
Placebo
干预措施: SAD: Pooled Placebo (Drug)
SAD: 30mg WVE-003
Single Ascending Dose - 30mg WVE-003
干预措施: SAD: 30mg WVE-003 (Drug)
SAD: 60mg WVE-003
Single Ascending Dose - 60mg WVE-003
干预措施: SAD: 60mg WVE-003 (Drug)
SAD: 90mg WVE-003
Single Ascending Dose - 90mg WVE-003
干预措施: SAD: 90mg WVE-003 (Drug)
MD: Placebo
Placebo
干预措施: MD: Placebo (Drug)
MD: 30mg WVE-003
Multiple Dose - 30mg WVE-003
干预措施: MD: 30mg WVE-003 (Drug)
结局指标
主要结局
Safety: Proportion of Patients With Treatment Emergent Adverse Events (TEAEs) Related to Study Drug
时间窗: Day 1 through Week 24 (single ascending dose Period 1); Day 1 through Week 28 (multi dose Period 2)
The primary outcome for this study was safety and is reported as the proportion of patients with TEAEs related to study drug.
次要结局
- Pharmacokinetics of WVE-003 in Plasma(Day 1 (single ascending dose Period 1); Day 1 and Day 113 (multi dose Period 2))
- Concentration of WVE-003 in Cerebrospinal Fluid (CSF)(28 days post-dose during Period 1 (P1:Day29); 28 days post last dose during Period 2 (P2: Day141))