An Open-label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered PrP-siRNA in Adult Patients Diagnosed With Symptomatic Prion Disease.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 5
- 主要终点
- Frequency of adverse events
研究概览
简要总结
The purpose of this trial is to evaluate safety, tolerability, pharmacokinetics and pharmacodynamic impact of PrP-siRNA in symptomatic prion disease patients.
详细描述
This is a first-in-human, open label, single ascending dose study in participants with prion disease. The study will consist of a screening period of up to 2 weeks, administration of a single intrathecal dose of PrP-siRNA, and a 24-week follow-up period. Multiple dose levels will be tested. This trial also includes an observational arm in which participants will not receive investigational drug, and will be followed for an 8-week period after baseline.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •clinically manifested symptoms of prion disease, in the opinion of the investigator;
- •a diagnosis of probable prion disease according to CDC criteria;
- •a positive CSF RT-QuIC or PRNP genetic test;
- •no more than moderate functional impairment as quantified by an MRC-PDRS score ≥15; and
- •availability of a study partner to assist with study procedures.
排除标准
- •contraindication to LP; or
- •recent participation in a different prion disease clinical trial.
- •Additional inclusion and exclusion criteria apply and will be evaluated at screening.
研究组 & 干预措施
Arm 1: Observational
In Arm 1, participants will undergo lumbar punctures and other study activities at baseline (Week 0) and at Week 4 and Week 8. Investigational drug will not be administered. We will prioritize enrollment in Arm 2; Arm 1 will be open to enrollment whenever Arm 2 is not open to enrollment.
Arm 2: Single ascending dose
In Arm 2, participants will be admitted to the clinical trial center and receive a single intrathecal dose of PrP-siRNA. Dose levels to be sequentially evaluated are 50, 100, and 200 mg. Patients will be discharged on Day 2 and then periodically return to the study center on an outpatient basis at Week 1, 2, 4, 8, 12 and 24 for safety monitoring and study activities through the 24 week follow up period.
干预措施: PrP-siRNA (Drug)
结局指标
主要结局
Frequency of adverse events
时间窗: Baseline to week 24
次要结局
- CSF PrP concentration(4 weeks post-dose)
- CSF PrP concentration(8 weeks post-dose)
- CSF PrP concentration(12 weeks post-dose)
- CSF PrP concentration(24 weeks post-dose)
- Plasma concentration of PrP-siRNA(4 hours post-dose)
- Plasma concentration of PrP-siRNA(24 hours post-dose)
- Plasma concentration of PrP-siRNA(4 weeks post-dose)
- CSF concentration of PrP-siRNA(4 weeks post-dose)
- Change in CSF PrP over time(Baseline to week 24)