| Summary |
Study Period: Approximately 35 months from the date of approval by the Institutional Review Board (IRB) (However, it can be extended depending on the subject enrollment period or the time to study closure)
Indication: Patients who were diagnosed with Parkinson's disease ≥ 5 years ago
Purpose: To find the maximum tolerable dose and evaluate the safety and exploratory efficacy of allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC) therapy in patients who were diagnosed with Parkinson's disease ≥ 5 years ago, as a treatment for delaying or stopping the progression of Parkinson's disease or inducing recovery of damaged brain.
Number of Subjects: It aims to recruit up to 12 subjects for the dose-escalation study with two phases.
[Low dose] Dose: 3.15X10^6 cells/body | Study group(A9-DPC): 6 subjects [High dose] Dose: 6.30X10^6 cells/body | Study group(A9-DPC): 6 subjects
Study Design: Single center, open, single dosing, dose-escalation, phase 1/2a study
Endpoints:
[Primary Safety Endpoints]
1. Occurrence of treatment-emergent adverse events (TEAEs) after administration of the IP
2. Failure or rejection of transplantation and occurrence of bleeding and infection at Week 12 (3 months), Week 24 (6 months), Week 48 (12 months) and Week 96 (24 months) after administration of the IP
3. Occurrence of adverse event of special interest (AESI)* after administration of the IP
AESI: a) death, b) generation of a neoplasm or malignant tumor in tissues or organs, c) onset of an immune reaction including worsening of a previous autoimmune disease or new occurrence, and d) other delayed adverse events related to this embryonic stem cell treatment.
[Exploratory Efficacy Endpoints]
1. Change in the following clinical endpoints at Week 4 (1 month), Week 12 (3 months), Week 24 (6 months), Week 36 (9 months), Week 48 (12 months), Week 72 (18 months) and Week 96 (24 months) after administration of the IP compared to screening
① MDS-UPDRS Total Score, part Ⅲ & part Ⅳ (defined on/off)
Defined-on condition: condition that the most positive functional effect, as agreed by the subject and the tester, after treatment with drugs for controlling the symptoms of Parkinson's disease
Defined-off condition: condition after 12 hours off drugs for controlling the symptoms of Parkinson's disease ② K-MMSE ③ Seoul Neuropsychological screening battery (SNSB, Screening & Week 96 (24 months))
2. Change in the following clinical endpoints at Week 4 (1 month), Week 12 (3 months), Week 24 (6 months), Week 36 (9 months), Week 48 (12 months), Week 72 (18 months) and Week 96 (24 months) after administration of the IP compared to baseline
K-MoCA
Parkinson's Questionnaire (PDQ-39)
Schwab and England ADL scale (SEADL)
Non-Motor Symptoms Scale for Parkinson's Disease (NMS)
3. Change in Graft size through MRI at Week 12 (3 months), Week 24 (6 months), Week 48 (12 months) and Week 96 (24 months) after administration of the IP compared to baseline
4. Change in Cerebral FDG uptake and Striatal FDG uptake at Week 48 (12 months) and Week 96 (24 months) after administration of the IP compared to baseline
5. Change in density of dopamine transporters as measured by FP-CIT PET at Week 48 (12 months) and Week 96 (24 months) after administration of the IP compared to screening
6. Percentage of subjects who used concomitant medication related to Parkinson-mobility or Parkinson-Non-mobility during the whole clinical trial period and change in dose of each concomitant medication (per component) at 12 week intervals compared to the dose of each concomitant medication (per component) from the date of administration of IP to Week 12.
[Other Safety Endpoints]
1. Vital signs
2. Laboratory tests
3. Physical examination |
