Parkinson Disease, Parkinson's Disease
Conditions
Keywords
PD, AAV, Adeno-associated Virus, Gene therapy
Brief summary
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.
Interventions
DRUGIPS101A
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.
Sponsors
Innopeutics Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. 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. 2. 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. 3. 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. 4. 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. 5. Subjects with a Hoehn \& Yahr stage of 4 or 5 in the off state at the Screening Visit.
Exclusion criteria
1. 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. 2. Subjects with a Korean Mini-Mental State Examination (K-MMSE) score ≤ 24 at the Screening assessment. 3. 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. 4. Subjects who do not meet the diagnostic criteria for Parkinson's disease dementia but present with major visual hallucinations, as judged by the Investigator. 5. Subjects with drug-induced parkinsonism, confirmed by clinical history and/or medical records, and determined by the Investigator. 6. Subjects who are judged by the investigator to be unsuitable for participation in this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Evaluation: dose-limiting toxicity (DLT) | Baseline to Week 8 | Frequency and proportion of subjects who developed dose-limiting toxicity (DLT) |
| Safety Evaluation: Severity and frequency of reported adverse events | Baseline to Week 52 | Assess severity and frequency of reported adverse events |
| Safety Evaluation: clinically-relevant changes in laboratory testing assessed by medical personnel | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Each symptom is rated on a scale of 0 to 4, with higher scores indicating more severe Parkinson's disease. |
| Change from Baseline in Hoehn & Yahr stage (defined on/off) | Weeks 1, 4, 12, 24, 36, and 52. | This scale is classified from 0 to 5, with a higher score indicating a more severe degree of Parkinson's disease. |
| Change from Baseline in Non-Motor Symptoms Scale for Parkinson's Disease (NMSS) | Weeks 4, 12, 24, 36, and 52. | 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. |
| Change from Baseline in Parkinson's Disease Questionnaire (PDQ-39) scores | Weeks 4, 12, 24, 36, and 52 | The scale consists of 800 points, and a higher score indicates a lower quality of life. |
| Distribution evaluation of IPS101A (AAV9 vector distribution evaluation)-CSF | Baseline to Week 52 | After IP administration, the detection of AAV genome was measured using q-PCR. |
| Distribution evaluation of IPS101A (AAV9 vector distribution evaluation)-blood | Baseline to Week 52 | After IP administration, the detection of AAV genome was measured using q-PCR. |
| Evaluation of humoral (anti-AAV9 antibodies) and cellular (IFN-γ activity) immune responses to AAV9 | Baseline to Week 52 | After IP administration, the detection of AAV genome was measured using ELISA |
| Assessment of AAV9 shedding in biological specimens-urine | Baseline to Week 52 | After IP administration, the detection of AAV genome was measured using q-PCR. |
Countries
South Korea
Contacts
CONTACTChoLong Park
CONTACTTae-gyun Kim
Outcome results
None listed