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
- 41
- 主要终点
- Change From Baseline in Modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I Total Score 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.
研究组 & 干预措施
Placebo
Participants received TAK-341 matching placebo intravenous (IV) infusions, once every 4 weeks (Q4W) for 52 weeks.
干预措施: Placebo (Drug)
TAK-341
Participants received TAK-341, IV Q4W for 52 weeks. An early set of participants initially received 2400 milligrams (mg) to determine pharmacokinetic (PK) parameters. Following the early participants, a dose of 2000 mg was given until the data from the PK participants became available. All participants then received 2400 mg until the end of treatment at 52 weeks.
干预措施: TAK-341 (Drug)
结局指标
主要结局
Change From Baseline in Modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I Total Score at Week 52
时间窗: Baseline, Week 52
UMSARS Part I (historical review) is a 12-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 autonomic dysfunction. In this study, the UMSARS was modified to exclude the sexual function item. Thus, total 11 items were assessed. Each item was initially scored on a scale from 0 (normal) to 4 (severe); ratings of normal (0) and mild (1) were then combined and recorded as 0, making minimum score 0 and maximum score 3. The investigator rated the average functional situation for the past 2 weeks according to findings from the participant and caregiver interview and indicated the score that best fit with the participant's status. The total score is a sum of scores from all domains and range from 0 to 33. Higher scores indicate worse impairment.
次要结局
- Change From Baseline in 11-item UMSARS at Week 52(Baseline, Week 52)
- Change From Baseline in the UMSARS Total Score (UMSARS Part I + Part II) at Week 52(Baseline, Week 52)
- Change From Baseline in UMSARS Part I 11-Item Score at Week 52(Baseline, Week 52)
- Maximum Observed Steady State Serum Concentration (Cmax) for TAK-341(On Day 57- immediately before end of infusion (EOI) (60 minutes), 6 hours and 24 hours.)
- Time to Maximum Steady State Concentration (Tmax) for TAK-341(On Day 57- immediately before EOI (60 minutes), 6 hours and 24 hours.)
- Change From Baseline in UMSARS Part II at Week 52(Baseline, Week 52)
- Change From Baseline on Clinical Global Impression-Severity (CGI-S) Score(Baseline, Week 24 and Week 52)
- Change From Baseline in Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT) Total Score(Baseline, Week 24 and Week 52)
- Overall Survival (OS) at Week 52(At Week 52)
- Change From Baseline in Cerebrospinal Fluid (CSF) Free Alpha-Synuclein (αSYN)(Baseline, Week 52)
- Area Under the Serum Concentration Time Curve (AUCτ) at Steady State for TAK-341(On Day 57- immediately before EOI (60 minutes), 6 hours and 24 hours.)
- CSF Concentration of TAK-341(On Day 1, Day 85 and Day 365)
- Number of Participants With at Least One Adverse Event (AE)(Up to Week 61)
- Number of Participants With Anti-Drug Antibodies(Up to Week 61)