A Phase I Open-Label Dose-Escalation Study to Evaluate the Safety, Tolerability, and Efficacy of Autologous MitoCell (Adipose-Derived Mesenchymal Stem Cells) Transplantation in Subjects With Idiopathic Parkinson's Disease
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 9
- 主要终点
- Routine physical examinations
研究概览
简要总结
Primary Objective: To assess the safety profile of autologous MitoCell administered to subjects with idiopathic Parkinson's disease (PD)
Secondary Objective: To explore the efficacy and safety of MitoCell given as the recommended dose by stereotactic intrastriatal implantation
详细描述
MitoCell is an autologous stem cell product that cultures with the company's unique patented medium. The mechanism of action of MitoCell is to improve the brain microenvironment in neurodegenerative disease. MitoCell which like mesenchymal stem cells modulate the immune response, and secrete more BDNF and SDF-1 neurotrophic factors than regular stem cell products.Therefore, MitoCell can protect and repair damaged dopamine neurons (DA) and stimulate DA regeneration.This project is a phase I open-label dose-escalation study to evaluate the safety, tolerability, and efficacy of autologous MitoCell intracranial transplantation in subjects with idiopathic Parkinson's disease which rating from stage 3 ~ 4 of modified Hoehn & Yahr staging.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of signed and dated informed consent form
- •Aged 45 to 70 years old (inclusive) at Screening
- •Idiopathic Parkinson's disease patients who meet the diagnostic criteria of the "Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease"
- •With at least 5 years since the diagnosis of Parkinson's disease
- •With responsiveness to levodopa or dopa agonist. This is defined as improvement between ''Off'' and ''On'' MDS-UPDRS by at least 33% of the Motor MDS-UPDRS
- •Idiopathic Parkinson's disease of Stage 3 ~ 4 of modified Hoehn & Yahr staging during ''ON'' time
- •Stable Parkinsonian medications for at least 2 months prior to the Screening Visit
- •MRI not showing gross atrophy or any brain pathology other than PD
- •Mini-Mental State Examination (MMSE) ≧ 24
- •With score of the Beck Depression Inventory (BDI-II) < 29 and Hamilton Rating Scale for Depression (HAM-D-17) < 25
排除标准
- •Atypical or secondary Parkinsonism
- •With neurodegenerative disorders other than PD
- •Unable to receive MRI or PET scanning
- •With any concomitant disorder that would contraindicate coagulation, general anesthesia, or stereotactic neurosurgery
- •Received any other investigational agent within 4 weeks prior to Screening
- •History of intracranial surgeries or implantation of a device for Parkinson's disease 2 years prior to Screening
- •Major surgery within the previous 6 months at Screening
- •Significant cardiovascular disease, including:
- •New York Heart Association (NYHA) class III or IV congestive heart failure
- •Uncontrolled hypertension: Blood pressure >140/90 mmHg
- •History of serious ventricular arrhythmia
- •Malignancy within 2 years prior to Screening
- •Any diagnosis of autoimmune disease or immune compromised state and requiring systemic steroid or immunosuppressive treatment
- •Any other severe systemic disorder, including history of schizophrenia or other psychotic disorders, stroke, seizure, traumatic brain injury, or central nervous system infection, which judged by the investigator that entering the trial may be detrimental to the subject
- •Psychiatric, addictive or any other disorder that compromises ability to give a truly informed consent and perform all study assessments
- •Positive in any of the following regulatory authority-licensed screening tests:
- •HIV antigen/antibody combo test
- •Anti-HCV test
- •Hepatitis B surface antigen (HBsAg) test
- •Rapid plasma reagin (RPR) test
- •HIV-1 nucleic acid test (NAT)
- •Any of the following hematologic abnormalities:
- •Hemoglobin < 9.0 g/dL,
- •ANC < 1,500/μL
- •Platelets < 100,000/μL
- •Any of the following serum biochemistry abnormalities:
- •Total bilirubin > 1.5 × ULN
- •AST or ALT > 2.5 × ULN
- •r-GT > 2.5 × ULN
- •ALP > 2.5 × ULN
- •serum albumin < 3.0 g/dL
- •creatinine > 1.5 × ULN
- •Female subject who is lactating or has positive serum or urine pregnancy test at Screening Visit
- •Female subject with childbearing potential or male subject with female spouse/partner with childbearing potential who refuses to adopt at least two forms of birth control (at least one of which must be a barrier method) from Screening until Final/Early Termination Visit. Acceptable forms include:
- •Established use of oral, injected or implanted hormonal methods of contraception
- •Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- •Barrier methods of contraception: condom, or occlusive cap (diaphragm or cervical/vault caps)
- •With any condition judged by the investigator that entering the trial may be detrimental to the subject
研究组 & 干预措施
Single Arm Study
Autologous MitoCell Transplantation in Subjects with Idiopathic Parkinson's Disease
干预措施: Aadipose-Derived Mesenchymal Stem Cells (Biological)
结局指标
主要结局
Routine physical examinations
时间窗: within 48 weeks after MitoCell transplantation
Safety of Mitocell will be assessed by routine physical examinations. Physical examination conducted in this study will include general appearance, skin, eyes, ears, nose,throat, head and neck, heart, chest and lungs, abdomen, extremities, lymph nodes, musculoskeletal,neurological, etc.
Changes in vital signs: blood pressure [Safety of Mitocell]
时间窗: within 48 weeks after MitoCell transplantation
Changes in blood pressure during the study , measured as systolic and diastolic blood pressure (in mmHg)
Changes in physical examinations: clinical standard neurological examination [Safety of Mitocell]
时间窗: within 48 weeks after MitoCell transplantation
Clinical standard neurological examination by study investigator. Changes in motor function, sensory function, cranial nerve function (visual fields), cortical functions and reflexes are followed in the examination, scored as normal - abnormal without clinical relevance - abnormal with clinical relevance
Grading of Adverse Events
时间窗: within 48 weeks after MitoCell transplantation
Grading will be assessed using NCI CTCAE, version 5.0.
Changes in vital signs: body temperature [Safety of Mitocell]
时间窗: within 48 weeks after MitoCell transplantation
Changes in body temperature during the study (in degrees celsius)
Changes in clinical laboratory safety screen: International Normalized Ratio (INR) [Safety of Mitocell]
时间窗: within 48 weeks after MitoCell transplantation
Changes in laboratory variables for haematology: INR (standardized prothrombin time) to determine the effects of oral anticoagulants on the clotting system. Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance"
Electrocardiogram (ECG)
时间窗: within 48 weeks after MitoCell transplantation
Safety of Mitocell will be assessed by any clinically significant abnormalities on ECG results as compared to Baseline. A standard 12-lead ECG was measured by using ECG machine that automatically measured PR, QRS, QT, and QTcF intervals.
Magnetic Resonance Imaging (MRI)
时间窗: within 48 weeks after MitoCell transplantation
Safety of Mitocell will be assessed by any clinically significant abnormalities on MRI scans as compared to Baseline.
Changes in vital signs: pulse rate [Safety of Mitocell]
时间窗: within 48 weeks after MitoCell transplantation
Changes in pulse rate during the study (in beats per minute)
Changes in clinical laboratory safety screen: haematology - hemoglobin [Safety of Mitocell]
时间窗: within 48 weeks after MitoCell transplantation
Changes in laboratory variables for haematology: hemoglobin (g/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance"
Changes in clinical laboratory safety screen: white blood cell (WBC) counts [Safety of Mitocell]
时间窗: within 48 weeks after MitoCell transplantation
Changes in laboratory variables for haematology: Cell counts (10E9/L) for total WBC, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance"
Changes in clinical laboratory safety screen: Platelet count [Safety of Mitocell]
时间窗: within 48 weeks after MitoCell transplantation
Changes in laboratory variables for haematology: Platelet count (10E9/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance"
Changes in clinical laboratory safety screen: activated partial thromboplastin time (aPTT) [Safety of Mitocell]
时间窗: within 48 weeks after MitoCell transplantation
Changes in laboratory variables for haematology: aPTT (sec) . Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance"
次要结局
- PDQ-39 (Parkinson's Disease Questionnaire)(at 12, 24, 48 weeks)
- Hamilton Depression Rating Scale (HAM-D-17) scores(at 48 weeks)
- Modified Hoehn & Yahr staging(at 12, 24, 48 weeks)
- Mini Mental State Examination (MMSE) Scores(at 48 weeks)
- MDS-UPDRS (Movement Disorder Society unified Parkinson's disease rating scale)(at 12, 24, 48 weeks)
- 18F-DOPA PET(at 48 weeks)
- levodopa equivalent daily dose (LEDD)(at 12, 24, 48 weeks)
- Beck Depression Inventory (BDI-II) scores(at 48 weeks)