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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
6
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.
Severance Hospital
Seoul, South Korea
Safety Evaluation: dose-limiting toxicity (DLT)
Frequency and proportion of subjects who developed dose-limiting toxicity (DLT)
Time frame: Baseline to Week 8
Safety Evaluation: Severity and frequency of reported adverse events
Assess severity and frequency of reported adverse events
Time frame: Baseline to Week 52
Safety Evaluation: clinically-relevant changes in laboratory testing assessed by medical personnel
The clinical significance of laboratory test results after administration of a clinical trial drug is confirmed by comparing them with those before administration.
Time frame: Baseline to Week 52
Safety Evaluation: clinically-relevant changes in physical exams assessed by medical personnel
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.
Time frame: Baseline to Week 52
Change from Baseline in Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores (defined on/off)
Each symptom is rated on a scale of 0 to 4, with higher scores indicating more severe Parkinson's disease.
Time frame: Baseline to Weeks 4, 12, 24, 36, and 52.
Change from Baseline in Hoehn & Yahr stage (defined on/off)
This scale is classified from 0 to 5, with a higher score indicating a more severe degree of Parkinson's disease.
Time frame: Weeks 1, 4, 12, 24, 36, and 52.
Change from Baseline in Non-Motor Symptoms Scale for Parkinson's Disease (NMSS)
This scale is rated on a scale of severity (0-3 points) and frequency (1-4 points). A higher score indicates more severe Parkinson's disease.
Time frame: Weeks 4, 12, 24, 36, and 52.
Change from Baseline in Parkinson's Disease Questionnaire (PDQ-39) scores
The scale consists of 800 points, and a higher score indicates a lower quality of life.
Time frame: Weeks 4, 12, 24, 36, and 52
Distribution evaluation of IPS101A (AAV9 vector distribution evaluation)-CSF
After IP administration, the detection of AAV genome was measured using q-PCR.
Time frame: Baseline to Week 52
Distribution evaluation of IPS101A (AAV9 vector distribution evaluation)-blood
After IP administration, the detection of AAV genome was measured using q-PCR.
Time frame: Baseline to Week 52
Evaluation of humoral (anti-AAV9 antibodies) and cellular (IFN-γ activity) immune responses to AAV9
After IP administration, the detection of AAV genome was measured using ELISA
Time frame: Baseline to Week 52
Assessment of AAV9 shedding in biological specimens-urine
After IP administration, the detection of AAV genome was measured using q-PCR.
Time frame: Baseline to Week 52
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