A Randomized, Double-blind, Placebo-controlled Study, to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally Administered Single Ascending Doses of ALN-HTT02 in Adult Patients With Huntington's Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 66
- 试验地点
- 20
- 主要终点
- Frequency of Adverse Events (AEs) in the Double-blind Part of the Study
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of single or repeat doses of ALN-HTT02.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 25 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has stage 2 or early Stage 3 Huntington's disease (HD), per the Huntington's Disease Integrated Staging System (HD-ISS)
排除标准
- •Has significant structural or degenerative neurologic disease other than Huntington's Disease (HD) at screening
- •Has primary or secondary immune compromise at screening due to infections, medical conditions, or chronic therapies
- •Has alanine aminotransferase or aspartate aminotransferase >2× upper limit of normal (ULN)
- •Has an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m^2 at screening
- •Has received an investigational agent within the last 1 year or 5 half-lives (if known)
- •Note: other protocol defined inclusion / exclusion criteria apply
研究组 & 干预措施
Placebo + ALN-HTT02
Participants will be administered a single dose of placebo during the Double-blind Part of the study. Participants will have the option to receive a single dose of ALN-HTT02 during the Open-label Part of the study. Participants have the option to receive repeat doses of ALN-HTT02 in the OLE Part of the study.
干预措施: ALN-HTT02 (Drug)
Placebo + ALN-HTT02
Participants will be administered a single dose of placebo during the Double-blind Part of the study. Participants will have the option to receive a single dose of ALN-HTT02 during the Open-label Part of the study. Participants have the option to receive repeat doses of ALN-HTT02 in the OLE Part of the study.
干预措施: Placebo (Drug)
ALN-HTT02
Participants will be administered a single dose of ALN-HTT02 during the Double-blind Part of the study. Participants who received ALN-HTT02 in the Double-blind part of the study will not receive an additional dose during the Open-label Part of the study. Participants have the option to receive repeat doses of ALN-HTT02 in the Open-label Extension (OLE) Part of the study.
干预措施: ALN-HTT02 (Drug)
结局指标
主要结局
Frequency of Adverse Events (AEs) in the Double-blind Part of the Study
时间窗: Up to 12 months
Frequency of AEs in the Open-label Part of the Study
时间窗: Up to 12 months
Frequency of AEs in the OLE Part of the Study
时间窗: Up to 36 months
次要结局
- Change from Baseline in Levels of Mutant Huntingtin (mHTT) in Cerebrospinal Fluid (CSF)(Baseline up to Month 12 in the Double-blind Part of the study; Baseline up to Month 12 in the Open-label Part of the study)
- Concentrations of ALN-HTT02 in Plasma(Up to Month 12 in the Double-blind Part of the study; Up to Month 12 in the Open-label Part of the study)
- Concentrations of ALN-HTT02 in Cerebrospinal Fluid (CSF)(Up to Month 12 in the Double-blind Part of the study; Up to Month 12 in the Open-label Part of the study)
- Concentrations of ALN-HTT02 in Urine(Up to Month 12 in the Double-blind Part of the study; Up to Month 12 in the Open-label Part of the study)
- Change from Baseline in Levels of Mutant Huntingtin (mHTT) in Cerebrospinal Fluid (CSF)(Baseline up to Month 12 in the Double-blind Part of the study; Baseline up to Month 12 in the Open-label Part of the study ; Baseline up to Month 36 in the OLE Part of the study)
- Concentrations of ALN-HTT02 in Plasma(Up to Month 12 in the Double-blind Part of the study; Up to Month 12 in the Open-label Part of the study; Up to Month 36 in the OLE Part of the study)
- Concentrations of ALN-HTT02 in Urine(Up to Month 12 in the Double-blind Part of the study; Up to Month 12 in the Open-label Part of the study; Up to Month 36 in the OLE Part of the study)
- Concentrations of ALN-HTT02 in Cerebrospinal Fluid (CSF)(Up to Month 12 in the Double-blind Part of the study; Up to Month 12 in the Open-label Part of the study ; Up to Month 36 in the OLE Part of the study)