A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous TAK-341 in Subjects With Multiple System Atrophy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 158
- 试验地点
- 81
- 主要终点
- Change from Baseline in a Modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I at Week 52
研究概览
简要总结
The main aim is to see how TAK-341 works after 52 weeks in participants with multiple system atrophy as measured by the Unified Multiple System Atrophy Rating Scale Part I (UMSARS).
The study will enroll approximately 138 patients. Participants will receive a total of 13 intravenous infusions every 4 weeks approximately, these may be either of TAK-341 or placebo, after each infusion some blood samplings will be taken and other assessments completed.
This trial will be conducted in North America, Europe and Asia.
详细描述
The drug being tested in this study is called TAK-341. The study will evaluate the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of intravenous (IV) TAK-341 in participants with multiple system atrophy (MSA).
The study will enroll approximately 158 participants. The study comprises a screening period of up to 42 days (6 weeks), a 52-week double-blind treatment period, and a follow-up safety visit. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant, care provider and investigator during the study:
- TAK-341
- Placebo
The change from baseline in UMSARS will be measured at Week 52 post-dose.
This multi-center trial will be conducted worldwide. The duration of treatment in this study will be 52 weeks. Participants will make a follow-up visit to the site after approximately 90 days after the last dose of study treatment.
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
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnostic:
- •The participant has a diagnosis of possible or probable MSA using the modified Gilman et al, 2008 diagnostic criteria.
- •The participant's onset of first MSA symptoms occurred ≤4 years before screening, as assessed by the investigator.
- •Evidence of MSA specific symptoms and deficits as measured by the UMSARS scale.
排除标准
- •Medical History:
- •1. The participant has any contraindication to study procedures.
- •Diagnostic Assessments:
- •Presence of confounding diagnosis and/or conditions that could affect participant's safety during the study per investigator judgement.
- •The participant's participation in a previous study of a disease-modifying therapy (with proven receipt of active treatment) will compromise the interpretability of the data from the present study, per consultation with medical monitor or designee.
- •1. The participant has participated in another study investigating active or passive immunization against α-synuclein (αSYN) for progressive disease (PD) or MSA, or has had immunoglobulin G therapy, within 6 months before screening.
结局指标
主要结局
Change from Baseline in a Modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I at Week 52
时间窗: Up to 52 weeks
UMSARS Part I (historical review) is a 11-item scale that was adapted from the Unified Parkinson's Disease Rating Scale (UPDRS) and is used to assess activities related to motor disability and related to autonomic dysfunction. Each item is scored from 0 (normal) to 3 (severe). The total score is a sum of scores from all domains and can range from 0 to 33. Higher scores mean poorer health.
次要结局
- Clinical Global Impression-Severity (CGI-S) Score(Up to 52 weeks)
- Overall Survival (OS)(Up to 52 weeks)
- Change From Baseline in UMSARS Total Score (UMSARS Part I + Part II) at Week 52(Up to 52 weeks)
- Change From Baseline in 11-item UMSARS at Week 52(Up to 52 weeks)
- Change from Baseline on Levels of Cerebrospinal Fluid (CSF) Free Alpha-synuclein (αSYN)(Up to 52 weeks)
- Change From Baseline in UMSARS Part I at Week 52(Up to 52 weeks)
- Change From Baseline in Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT) Total Score(Up to 52 weeks)
- Change From Baseline in UMSARS Part II at Week 52(Up to 52 weeks)
- Cmax: Maximum Observed Serum Concentration for TAK-341(Pre-dose on Days 1, 29, 57, 85, 169, 253, 337; at multiple timepoints (up to 24 hours) post-dose on Days 1, 57, 85, 169, 337; anytime once on Days 365, 427 or at early termination (Day 57 applicable to only early PK cohorts))
- AUCτ: Area Under the Concentration-time Curve During a Dosing Interval in Serum for TAK-341(Pre-dose on Days 1, 29, 57, 85, 169, 253, 337; at multiple timepoints (up to 24 hours) post-dose on Days 1, 57, 85, 169, 337; anytime once on Days 365, 427 or at early termination (Day 57 applicable to only early PK cohorts))
- CSF Concentration of TAK-341(Pre-dose on Days 1, 85 (applicable to only early PK cohorts), and 365)
- Number of Participants With at Least one Adverse Event (AE)(Up to 52 weeks)
- Number of Participants With Antidrug Antibody(Up to 52 weeks)
- Tmax: Time of First Occurrence of Cmax in Serum for TAK-341(Pre-dose on Days 1, 29, 57, 85, 169, 253, 337; at multiple timepoints (up to 24 hours) post-dose on Days 1, 57, 85, 169, 337; anytime once on Days 365, 427 or at early termination (Day 57 applicable to only early PK cohorts))