A Prospective Exploratory Study of the Safety and Preliminary Efficacy of the α-Syn H21 Monoclonal Antibody in Patients With Multiple System Atrophy
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Incidence of treatment-emergent adverse events
研究概览
简要总结
Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by autonomic dysfunction, parkinsonism, and cerebellar ataxia. Abnormal aggregation of alpha-synuclein is believed to play an important role in disease progression. The α-Syn H21 monoclonal antibody is designed to selectively bind pathological alpha-synuclein aggregates and may reduce their spread and related neuroinflammation.
This single-center, prospective, exploratory study will evaluate the safety, tolerability, and preliminary efficacy of the α-Syn H21 monoclonal antibody in patients with MSA. Participants will receive intravenous infusions of H21 every 4 weeks for 3 doses and will be followed for 12 weeks. Clinical symptoms, laboratory tests, imaging findings, and adverse events will be assessed to determine whether H21 may provide clinical benefit and support future larger studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 45 to 75 years, male or female
- •Diagnosis of Multiple System Atrophy meeting current clinical diagnostic criteria for probable or possible MSA
- •Disease duration of 2 years or less from onset of motor or autonomic symptoms
- •Clinically stable disease without significant fluctuation or acute worsening within 4 weeks before enrollment
- •Able to comply with study procedures and follow-up assessments
- •Mini-Mental State Examination (MMSE) score not consistent with significant dementia
- •Willing and able to provide written informed consent
排除标准
- •History or presence of other neurological disorders that may interfere with study assessments, including Parkinson's disease, progressive supranuclear palsy, corticobasal degeneration, or stroke
- •Severe cognitive impairment or psychiatric disorder, including clinically significant depression or anxiety
- •Severe cardiac, hepatic, renal, or other major systemic disease
- •History of severe hypersensitivity to monoclonal antibody therapies Pregnant or breastfeeding women
- •Women or men unwilling to use effective contraception during the study
- •Participation in another clinical trial or receipt of investigational treatment within 3 months before enrollment
- •Any other condition that, in the investigator's judgment, would make participation inappropriate
结局指标
主要结局
Incidence of treatment-emergent adverse events
时间窗: From first dose through Week 12
Incidence, severity, and relationship of adverse events (AEs) and serious adverse events (SAEs) to study treatment.
Change from Baseline in Unified Multiple System Atrophy Rating Scale (UMSARS) Total Score (Parts I-IV)
时间窗: Baseline, Week 4, Week 8, and Week 12
Change from baseline in the total score and subscale scores of the Unified Multiple System Atrophy Rating Scale (UMSARS Parts I-IV). The UMSARS is a clinician-administered scale used to assess disease severity in patients with multiple system atrophy. Total scores are derived from Parts I-IV, with higher scores indicating greater disease severity and worse clinical status. The total score ranges from 0 to 249, with higher scores indicating more severe impairment.
Change from baseline in DAT-PET/MRI measures of striatal dopamine transporter uptake and brain structural changes
时间窗: Baseline and Week 12
Change from baseline in DAT-PET/MRI imaging parameters, including brain metabolic and structural changes.
次要结局
- Change from Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score(Baseline, Week 4, Week 8, and Week 12)
- Change in Patient Global Impression of Improvement (PGI-I) Score(Baseline, Week 4, Week 8, and Week 12)
- Change from Baseline in Mini-Mental State Examination (MMSE) Score(Baseline, Week 4, Week 8, and Week 12)
- Change from Baseline in Hamilton Depression Rating Scale (HAMD) Score(Baseline, Week 4, Week 8, and Week 12)
- Change from Baseline in Hamilton Anxiety Rating Scale (HAMA) Score(Baseline, Week 4, Week 8, and Week 12)
- Change from Baseline in Parkinson's Disease Sleep Scale-2 (PDSS-2) Score(Baseline, Week 4, Week 8, and Week 12)
- Change from Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Score(Baseline, Week 4, Week 8, and Week 12)
- Number of Participants With Clinically Significant Abnormal Laboratory Values(Baseline, Week 4, Week 8, and Week 12)
- Maximum Observed Serum Concentration (Cmax) of H21(During treatment through Week 12)
- Change from baseline in electrocardiogram parameters including heart rhythm, PR interval, QRS duration, and QTc interval(Baseline, Week 4, Week 8, and Week 12)
- Change in Blood Pressure After Infusion(Pre-dose and 10 minutes and 30 minutes after each infusion through Week 12)
- Change in Heart Rate After Infusion(Pre-dose and 10 minutes and 30 minutes after each infusion through Week 12)
- Change in Respiratory Rate After Infusion(Pre-dose and 10 minutes and 30 minutes after each infusion through Week 12)
- Serum Concentration of H21(During treatment through Week 12)
- Time to Maximum Observed Serum Concentration (Tmax) of H21(During treatment through Week 12)
- Area Under the Serum Concentration-Time Curve (AUC) of H21(During treatment through Week 12)
- Terminal Elimination Half-life (t1/2) of H21(During treatment through Week 12)