Evaluating Safety, Tolerability, and Efficacy of Autologous MitoCell Transplantation in Subjects With Idiopathic Parkinson's Disease

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Биопрепарат Aadipose-Derived Mesenchymal Stem Cells
  Stereotactic intrastriatal implantation of 3×10\^7 per hemisphere (total 6×10\^7 cells) or 1×10\^8 per hemisphere (total 2×10\^8 cells) autologous TM01-treated adipose-derived mesenchymal stem cells (MitoCell).

Первичные конечные точки

• Grading of Adverse Events [Срок оценки: within 48 weeks after MitoCell transplantation]
• Routine physical examinations [Срок оценки: within 48 weeks after MitoCell transplantation]
• Changes in physical examinations: clinical standard neurological examination [Safety of Mitocell] [Срок оценки: within 48 weeks after MitoCell transplantation]
• Changes in vital signs: blood pressure [Safety of Mitocell] [Срок оценки: within 48 weeks after MitoCell transplantation]
• Changes in vital signs: pulse rate [Safety of Mitocell] [Срок оценки: within 48 weeks after MitoCell transplantation]
• Changes in vital signs: body temperature [Safety of Mitocell] [Срок оценки: within 48 weeks after MitoCell transplantation]
• Changes in clinical laboratory safety screen: haematology - hemoglobin [Safety of Mitocell] [Срок оценки: within 48 weeks after MitoCell transplantation]
• Changes in clinical laboratory safety screen: Platelet count [Safety of Mitocell] [Срок оценки: within 48 weeks after MitoCell transplantation]
• Changes in clinical laboratory safety screen: white blood cell (WBC) counts [Safety of Mitocell] [Срок оценки: within 48 weeks after MitoCell transplantation]
• Changes in clinical laboratory safety screen: International Normalized Ratio (INR) [Safety of Mitocell] [Срок оценки: within 48 weeks after MitoCell transplantation]

Вторичные конечные точки (8)

• MDS-UPDRS (Movement Disorder Society unified Parkinson's disease rating scale) [Срок оценки: at 12, 24, 48 weeks]
• Modified Hoehn & Yahr staging [Срок оценки: at 12, 24, 48 weeks]
• 18F-DOPA PET [Срок оценки: at 48 weeks]
• levodopa equivalent daily dose (LEDD) [Срок оценки: at 12, 24, 48 weeks]
• PDQ-39 (Parkinson's Disease Questionnaire) [Срок оценки: at 12, 24, 48 weeks]
• Beck Depression Inventory (BDI-II) scores [Срок оценки: at 48 weeks]
• Hamilton Depression Rating Scale (HAM-D-17) scores [Срок оценки: at 48 weeks]
• Mini Mental State Examination (MMSE) Scores [Срок оценки: at 48 weeks]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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)
• HBV NAT
• HCV 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT05094011 · MITOCELL-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗