Dose-Escalation, Single-Center, Open-label Phase 1 Clinical Trial to Evaluate the Safety, Efficacy, and Pharmacokinetics of Adeno-associated Virus(AAV) Gene Therapy Product IPS101A in Parkinson's Disease Patients With Hoehn-Yahr Stage 4-5, Diagnosed in More Than 10 Years and Uncontrolled by All Available Monotherapy or Combination Therapy
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Safety Evaluation: dose-limiting toxicity (DLT)
研究概览
简要总结
The purpose of this study is to evaluate the dose-related safety and tolerability of IPS101A, an adeno-associated virus (AAV) gene therapy, in patients with Parkinson's disease who exhibit severe functional impairment corresponding to Hoehn & Yahr stages 4-5 and whose symptoms are not adequately controlled despite all available monotherapy and combination therapy options. In addition, the study aims to assess the maximum tolerated dose (MTD) of IPS101A, as well as its preliminary efficacy and pharmacokinetic (PK) characteristics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who have a diagnosis of Parkinson's disease that meets the UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria at the time of the Screening Visit.
- •Male or female subjects aged 50 to 80 years (inclusive) at the time of providing written informed consent, with a documented diagnosis of Parkinson's disease.
- •Subjects with a duration of Parkinson's disease of at least 10 years prior to the Screening Visit, based on medical history and/or medical records.
- •Subjects with Parkinson's disease that is inadequately controlled despite all available standard-of-care treatments, including monotherapy or combination therapy, as determined by the Investigator.
- •Subjects with a Hoehn & Yahr stage of 4 or 5 in the off state at the Screening Visit.
排除标准
- •Subjects with Parkinson's disease dementia (PDD) who meet the diagnostic criteria established by the Movement Disorder Society (MDS) Task Force, as determined by the Investigator at Screening.
- •Subjects with a Korean Mini-Mental State Examination (K-MMSE) score ≤ 24 at the Screening assessment.
- •Subjects in whom imaging findings suggestive of Parkinsonism-plus syndrome are observed on PET and MRI performed at the Screening Visit, as assessed by the Investigator and/or a qualified imaging specialist.
- •Subjects who do not meet the diagnostic criteria for Parkinson's disease dementia but present with major visual hallucinations, as judged by the Investigator.
- •Subjects with drug-induced parkinsonism, confirmed by clinical history and/or medical records, and determined by the Investigator.
- •Subjects who are judged by the investigator to be unsuitable for participation in this clinical trial.
研究组 & 干预措施
High dose(2.0 x 10^10 vg/patient)
IPS101A
干预措施: IPS101A (Drug)
Low dose (1.0 x 10^10 vg/patient)
IPS101A
干预措施: IPS101A (Drug)
结局指标
主要结局
Safety Evaluation: dose-limiting toxicity (DLT)
时间窗: Baseline to Week 8
Frequency and proportion of subjects who developed dose-limiting toxicity (DLT)
Safety Evaluation: Severity and frequency of reported adverse events
时间窗: Baseline to Week 52
Assess severity and frequency of reported adverse events
Safety Evaluation: clinically-relevant changes in laboratory testing assessed by medical personnel
时间窗: Baseline to Week 52
The clinical significance of laboratory test results after administration of a clinical trial drug is confirmed by comparing them with those before administration.
Safety Evaluation: clinically-relevant changes in physical exams assessed by medical personnel
时间窗: Baseline to Week 52
The results of the physical examination after administration of the clinical trial drug are compared with those before administration to determine whether clinically significant symptoms occur.
次要结局
- Change from Baseline in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores (defined on/off)(Baseline to Weeks 4, 12, 24, 36, and 52.)
- Change from Baseline in Hoehn & Yahr stage (defined on/off)(Weeks 1, 4, 12, 24, 36, and 52.)
- Change from Baseline in Non-Motor Symptoms Scale for Parkinson's Disease (NMSS)(Weeks 4, 12, 24, 36, and 52.)
- Change from Baseline in Parkinson's Disease Questionnaire (PDQ-39) scores(Weeks 4, 12, 24, 36, and 52)
- Distribution evaluation of IPS101A (AAV9 vector distribution evaluation)-CSF(Baseline to Week 52)
- Distribution evaluation of IPS101A (AAV9 vector distribution evaluation)-blood(Baseline to Week 52)
- Evaluation of humoral (anti-AAV9 antibodies) and cellular (IFN-γ activity) immune responses to AAV9(Baseline to Week 52)
- Assessment of AAV9 shedding in biological specimens-urine(Baseline to Week 52)