A Single Center, Open, Single Dosing, Dose-escalation, Phase 1/2a Study to Evaluate the Safety and Exploratory Efficacy of Embryonic Stem Cell-derived A9 Dopamine Progenitor Cell (A9-DPC) Therapy in Patients With Parkinson's Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Occurrence of treatment-emergent adverse events (TEAEs) after administration of the IP
研究概览
简要总结
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: Up to 12 subjects. [Low dose] 3.15X10^6 cells/body: 6 subjects. [High dose] 6.30X10^6 cells/body: 6 subjects.
Study Design: Single center, open, single dosing, dose-escalation, phase 1/2a study
Endpoints:
[Primary Safety Endpoints]
- Occurrence of treatment-emergent adverse events (TEAEs) after administration of the IP
- Failure or rejection of transplantation and occurrence of bleeding and infection at Week 12 (3months), Week 24 (6months), Week 48 (12months) and Week 96 (24months) after administration of the IP
- 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.
详细描述
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: Up to 12 subjects [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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with Parkinson's disease based on UK PD Society Brain Bank criteria at the time of the screening visit
- •Patient with Parkinson's disease at the age of 50 to 75 years old at the time of the screening visit
- •Patient who was diagnosed with Parkinson' disease ≥ 5 years ago at the time of the screening visit
- •Patient on a stable dose of medicine such as levodopa for ≥ 3 months before screening who has wearing off for ≥ 2 hours a day or freezing of gait responding to dopamine supplement or motor complications such as dyskinesia
- •At least moderate impairment in activity of daily living (MDS-UPDRS part II ≥13)
- •Patient on a stabile dose of standard treatment for Parkinson's disease (e.g., levodopa, dopamine agonists, MAO-B inhibitors, amantadine, anticholinergics, etc.) for ≥ 3 months before screening
- •≥ 40% in L-dopa responsiveness at the time of the screening visit
- •Hoehn & Yahr stage ≥ 3 during the off state and stage ≤ 3 during the on state at the time of the screening visit
- •Decreased dopamine transporters as measured by FP-CIT PET at the time of the screening visit
- •Able to undergo MRI
- •Signed consent after being sufficiently informed of the study
排除标准
- •Parkinson's disease dementia based on the Movement Disorders Society Task Force criteria
- •Parkinsonism plus syndrome confirmed by PET and MRI images at the screening visit
- •Patient that does not meet the criteria for Parkinson's disease dementia but has major visual hallucination
- •Freezing of gait with no or ambiguous response to L-dopa
- •Drug-induced parkinsonism
- •History of uncontrolled seizure disorders within 24 weeks before screening
- •Congenital developmental delay
- •Past or current coagulation factor related diseases at the time of the screening visit
- •Ongoing malignancies at the time of the screening visit or diagnosis of malignancies within the past 5 years
- •Active tuberculosis, autoimmune disease, or decreased immunity at the time of the screening visit (treatment with chemotherapy within the past 3 years or white blood cell [WBC] <3X10^3 cells/µL)
- •Patient diagnosed with diabetes mellitus
- •Participation in another clinical trial within 4 weeks before screening
- •History of treatment with cell therapy, except for blood transfusion, before study participation
- •Side effects to anesthetics, contrast agents, etc.
- •Past or current clinically significant diseases in the liver (including liver transplant), kidney, respiratory system, cardiovascular system, etc. or clinically significant laboratory test results at the time of the screening visit
- •Platelet count < 5.0X10^4/microL
- •Serum creatinine > 1.5 mg/dL
- •eGFR < 60 mL/min/1.73 m^2
- •AST or ALT ≥ 3 x ULN (Upper Limit of Normal)
- •Total bilirubin ≥ 1.5 x ULN (Upper Limit of Normal)
- •Hepatitis B or C
- •Human immunodeficiency virus (HIV) positive
- •History of brain surgery
- •Pregnant and lactating woman
- •Positive pregnancy test at the time of screening; or woman of childbearing potential and man who plan a pregnancy during the study or who do not agree to use clinically appropriate methods of contraception* described below Hormone contraceptives (subdermal contraceptive implants, injections, oral contraceptives, etc.), intrauterine device (IUD) (or intra uterine system [IUS]), subject's or partner's surgical sterilization (vasectomy, tubal ligation, etc.), double barrier method (combined use of barrier methods such as cervical cap or diaphragm in combination with male condom)
- •Ineligible for other reasons based on the judgment of the investigator
研究组 & 干预措施
Low Dose Group
- IP Name : Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC)
- Study group : 6 subjects
- Dosage: 3.15X10^6 cells/body (6 tracks in total, 52.5X10^4 cells per track)
干预措施: Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC) Low Dose (Biological)
High Dose Group
- IP Name : Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC)
- Study group : 6 subjects
- Dosage: 6.30X10^6 cells/body (6 tracks in total, 105X10^4 cells per track)
干预措施: Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC) High Dose (Biological)
结局指标
主要结局
Occurrence of treatment-emergent adverse events (TEAEs) after administration of the IP
时间窗: Up to 96 Weeks (24 months) after IP administration
Present frequency and percentage by each dose group about occurrence of treatment-emergent adverse events (TEAEs) after administration of the IP
Occurrence of infection
时间窗: Week 96 (24 months)
Present frequency and percentage by each dose group about occurrence of infection at Week 96 (24 months) after administration of the IP
Failure or rejection of transplantation
时间窗: Week 96 (24 months)
Present frequency and percentage by each dose group about failure or rejection of transplantation at Week 96 (24 months) after administration of the IP
Occurrence of adverse event of special interest (AESI)* after administration of the IP
时间窗: Up to 96 Weeks (24 months) after IP administration
Present frequency and percentage by each dose group about 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.
Occurrence of bleeding
时间窗: Week 96 (24 months)
Present frequency and percentage by each dose group about occurrence of bleeding at Week 96 (24 months) after administration of the IP
Failure or rejection of transplantation
时间窗: Week 12 (3 months)
Present frequency and percentage by each dose group about failure or rejection of transplantation at Week 12 (3 months) after administration of the IP
Failure or rejection of transplantation
时间窗: Week 24 (6 months)
Present frequency and percentage by each dose group about failure or rejection of transplantation at Week 24 (6 months) after administration of the IP
Failure or rejection of transplantation
时间窗: Week 48 (12 months)
Present frequency and percentage by each dose group about failure or rejection of transplantation at Week 48 (12 months) after administration of the IP
Occurrence of bleeding
时间窗: Week 12 (3 months)
Present frequency and percentage by each dose group about occurrence of bleeding at Week 12 (3 months) after administration of the IP
Occurrence of bleeding
时间窗: Week 24 (6 months)
Present frequency and percentage by each dose group about occurrence of bleeding at Week 24 (6 months) after administration of the IP
Occurrence of bleeding
时间窗: Week 48 (12 months)
Present frequency and percentage by each dose group about occurrence of bleeding at Week 48 (12 months) after administration of the IP
Occurrence of infection
时间窗: Week 12 (3 months)
Present frequency and percentage by each dose group about occurrence of infection at Week 12 (3 months) after administration of the IP
Occurrence of infection
时间窗: Week 24 (6 months)
Present frequency and percentage by each dose group about occurrence of infection at Week 24 (6 months) after administration of the IP
Occurrence of infection
时间窗: Week 48 (12 months)
Present frequency and percentage by each dose group about occurrence of infection at Week 48 (12 months) after administration of the IP
次要结局
- Change in the K-MMSE(-Day 14 to -Day 4, Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96)
- Change in the Parkinson's Questionnaire (PDQ-39)(-Day 2, Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96)
- Change in density of dopamine transporters as measured by FP-CIT PET(-Day 14 to -Day 4, Week 48, Week 96)
- 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)(Day 0 (Postoperative day #0), Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96)
- Change in the K-MoCA(-Day 2, Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96)
- Change in the Schwab and England ADL scale (SEADL)(-Day 2, Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96)
- Change in the Seoul Neuropsychological screening battery (SNSB, Screening & Week 96 (24 months))(-Day 14 to -Day 4, Week 96)
- Hoehn & Yahr scale(Day 14 to -Day 4, Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96)
- Change in the MDS-UPDRS Total Score, part Ⅲ (defined on/off) & part Ⅳ(-Day 14 to -Day 4, Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96)
- Change in Cerebral FDG uptake and Striatal FDG uptake(-Day 2, Week 48, Week 96)
- Parkinson's Disease diary(Day 0 (POD #0), Week 48, Week 72, Week 96)
- Change in the Non-Motor Symptoms Scale for Parkinson's Disease (NMS)(-Day 2, Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96)
- Change in Graft size through MRI(-Day 2, Week 12, Week 24, Week 48, Week 96)