A Phase 1/2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered ION717 in Patients With Prion Disease
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 85
- 试验地点
- 26
- 主要终点
- Incidence of treatment-emergent adverse events.
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of intrathecal (IT) delivery of ION717.
详细描述
This is a first-in-human, multi-center study in participants with prion disease. The study will consist of a screening period of up to 6 weeks, a 30-week treatment period, a 142-week open-label extension period and a 32-week post-treatment period. Multiple dose levels will be tested.
The trial consists of three Regimens. Regimens 1 and 2 are fully enrolled. Participants in Regimens 1 and 2 received multiple doses of study drug (ION717 and placebo) during the 30-week double-blind treatment period; the order of doses (i.e. whether a given dose was ION717 or placebo) was blinded. Regimen 3 is open label.
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
- Double (Participant, Investigator)
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
- •A confirmed diagnosis of probable or definite prion disease.
- •Early-stage prion disease at the time of Screening.
- •Willing to meet all study requirements, including travel to Study Center, procedures, measurements and visits.
- •Patients must have a caregiver who is ≥ 18 years old and who is able and willing to facilitate the patient's involvement, to the best of their ability, for the duration of the trial; caregivers must also be able and willing to provide information about themselves and the patient for the duration of the trial.
- •Aged ≥ 18 at the time of informed consent.
排除标准
- •Clinically significant abnormalities in medical history, laboratory tests or physical examination that would render a patient unsuitable for inclusion.
- •Any contraindication or unwillingness to undergo an MRI.
- •Obstructive hydrocephalus, presence of a functional ventriculoperitoneal shunt for the drainage of cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter.
- •Known brain or spinal disease that would interfere with the LP process, CSF circulation or safety assessment.
- •Have any other condition, which, in the opinion of the Investigator would make the patient unsuitable for inclusion or could interfere with the patient participating in or completing the study.
研究组 & 干预措施
ION717, Regimen 3
Participants will receive multiple doses of ION717 during the 30-week treatment period and the 142-week open-label extension period.
干预措施: ION717 (Drug)
ION717 + Placebo, Regimen 1
Participants will receive multiple doses of study drug (ION717 and placebo) during the 30-week treatment period; the order of doses is blinded. Participants will then receive multiple doses of ION717 during the 142-week open-label extension period.
干预措施: Placebo (Drug)
ION717 + Placebo, Regimen 2
Participants will receive multiple doses of study drug (ION717 and placebo) during the 30-week treatment period; the order of doses is blinded. Participants will then receive multiple doses of ION717 during the 142-week open-label extension period.
干预措施: Placebo (Drug)
ION717 + Placebo, Regimen 1
Participants will receive multiple doses of study drug (ION717 and placebo) during the 30-week treatment period; the order of doses is blinded. Participants will then receive multiple doses of ION717 during the 142-week open-label extension period.
干预措施: ION717 (Drug)
ION717 + Placebo, Regimen 2
Participants will receive multiple doses of study drug (ION717 and placebo) during the 30-week treatment period; the order of doses is blinded. Participants will then receive multiple doses of ION717 during the 142-week open-label extension period.
干预措施: ION717 (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events.
时间窗: Baseline up to Week 33
次要结局
- Maximum Observed Plasma Concentration (Cmax) of ION717(on Day 1 and Week 9)
- Area Under the Plasma Concentration-time Curve (AUC) of ION717(on Day 1 and Week 9)
- Half-life (t1/2λz) of ION717 in Plasma(on Day 1 and Week 9)
- Cerebrospinal fluid (CSF) Concentration of ION717(Pre-dose and at multiple points post-dose up to Week 33)
- Amount of ION717 Excreted in Urine(Post-dose on Day 1)
- Percent Change from Baseline in Prion Protein (PrP) Concentration in CSF(Pre-dose and at multiple points post-dose up to Week 33)