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

Official title

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

Overview

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

Detailed description

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.

Interventions

• Biological 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).

Primary outcome measures

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

Secondary outcome measures (8)

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

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT05094011 · MITOCELL-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗