Phase 1 Clinical Trial to Evaluate the Safety, Efficacy, and Pharmacokinetics of IPS101A in Parkinson's Disease Patients

Официальное название

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

Обзор

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.

Вмешательства

• Препарат IPS101A
  The investigational product (IP) will be administered as a single dose. All subjects will receive stereotactic injections into the left and right substantia nigra of the midbrain, with one administration per side.

Первичные конечные точки

• Safety Evaluation: dose-limiting toxicity (DLT) [Срок оценки: Baseline to Week 8]
• Safety Evaluation: Severity and frequency of reported adverse events [Срок оценки: Baseline to Week 52]
• Safety Evaluation: clinically-relevant changes in laboratory testing assessed by medical personnel [Срок оценки: Baseline to Week 52]
• Safety Evaluation: clinically-relevant changes in physical exams assessed by medical personnel [Срок оценки: Baseline to Week 52]

Вторичные конечные точки (8)

• Change from Baseline in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores (defined on/off) [Срок оценки: Baseline to Weeks 4, 12, 24, 36, and 52.]
• Change from Baseline in Hoehn & Yahr stage (defined on/off) [Срок оценки: Weeks 1, 4, 12, 24, 36, and 52.]
• Change from Baseline in Non-Motor Symptoms Scale for Parkinson's Disease (NMSS) [Срок оценки: Weeks 4, 12, 24, 36, and 52.]
• Change from Baseline in Parkinson's Disease Questionnaire (PDQ-39) scores [Срок оценки: Weeks 4, 12, 24, 36, and 52]
• Distribution evaluation of IPS101A (AAV9 vector distribution evaluation)-CSF [Срок оценки: Baseline to Week 52]
• Distribution evaluation of IPS101A (AAV9 vector distribution evaluation)-blood [Срок оценки: Baseline to Week 52]
• Evaluation of humoral (anti-AAV9 antibodies) and cellular (IFN-γ activity) immune responses to AAV9 [Срок оценки: Baseline to Week 52]
• Assessment of AAV9 shedding in biological specimens-urine [Срок оценки: Baseline to Week 52]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

South Korea · 1 центр

• Severance Hospital — Seoul

Идентификаторы

NCT: NCT07371338 · IPS101A-10

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗