A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of ION464 Administered Intrathecally to Adults With Multiple System Atrophy
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 25
- 主要终点
- Number of Participants with Adverse Events (AEs)
研究概览
简要总结
The primary objectives are to evaluate the safety and tolerability of multiple doses of ION464 administered via intrathecal (IT) injection (Part 1) and to evaluate the long-term safety and tolerability of ION464 (Part 2) in participants with multiple system atrophy (MSA).
The secondary objectives are to evaluate the pharmacodynamic (PD) effect of ION464 on the level of a potential biomarker of target engagement (Parts 1 and 2) and to evaluate the pharmacokinetic (PK) profile of ION464 in serum (Part 1).
详细描述
This is a first-in-human, randomized, blinded, placebo-controlled, multiple-ascending-dose (MAD) study (Part 1) to evaluate the safety, tolerability, PK, and PD of ION464 in adult participants diagnosed with MSA with a long-term extension (LTE) (Part 2). The study will include up to approximately 40 participants. Part 1 of the study consists of a Screening Period of up to 6 weeks, a Treatment Period of 12 weeks, and a Follow-up Period of 24 weeks. The study duration for each participant in Part 2 will be approximately 96 weeks, which consists of a 72-week Treatment Period and a 24-week Follow-up Period.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Screening single-photon emission computed tomography (SPECT) with DaTscan™ (ioflupane I123 injection) results demonstrating loss (whether symmetric or asymmetric) of dopamine nerve terminals in the striatum consistent with neurodegenerative parkinsonism, as assessed with qualitative, visual read.
- •Diagnosed with probable or possible MSA, either parkinsonian-type (MSA-P) or cerebellar-type (MSA-C).
- •Must be able to walk unassisted for at least 10 meters (approximately 30 feet)
排除标准
- •Presence of cognitive dysfunction (defined as Montreal Cognitive Assessment (MoCA) score <25)
- •Family history of ataxia or parkinsonism and known genetic cause of ataxia or parkinsonism.
- •NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
研究组 & 干预措施
Part 2: ION464
ION464 will be administered at the same doses as Part 1 by IT injection, at regular intervals, for 72 weeks.
干预措施: ION464 (Drug)
Part 2: Placebo
ION464-matching placebo will be administered by IT injection, at regular intervals, for 72 weeks.
干预措施: Placebo (Drug)
Part 1: Placebo
ION464-matching placebo will be administered by IT injection at regular intervals over 12 weeks.
干预措施: Placebo (Drug)
Part 1: ION464
ION464 will be administered at multiple-ascending doses by IT injection at regular intervals over 12 weeks.
干预措施: ION464 (Drug)
结局指标
主要结局
Number of Participants with Adverse Events (AEs)
时间窗: Baseline up to approximately 36 weeks
Number of Participants with Serious Adverse Events (SAEs)
时间窗: Baseline up to approximately 36 weeks
次要结局
- Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of ION464(Baseline up to approximately 36 weeks)
- Change From Baseline in Cerebrospinal Fluid (CSF) Levels of Total alpha-synuclein (α-syn)(Baseline up to approximately 36 weeks)
- Serum Concentration of ION464(Baseline up to approximately 36 weeks)
- Maximum Observed Concentration (Cmax) of ION464(Baseline up to approximately 36 weeks)
- Time to Reach Maximum Observed Concentration (Tmax) of ION464(Baseline up to approximately 36 weeks)
研究者
Global Regulatory Affairs
Scientific
Ionis Pharmaceuticals Inc.