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

Primary Purpose

Idiopathic Parkinson's Disease

Status

Not yet recruiting

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Aadipose-Derived Mesenchymal Stem Cells

About this trial

This is an interventional treatment trial for Idiopathic Parkinson's Disease

Eligibility Criteria

45 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Arm Study

Arm Description

Autologous MitoCell Transplantation in Subjects with Idiopathic Parkinson's Disease

Outcomes

Primary Outcome Measures

Grading of Adverse Events

Grading will be assessed using NCI CTCAE, version 5.0.

Routine physical examinations

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 physical examinations: clinical standard neurological examination [Safety of Mitocell]

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

Changes in vital signs: blood pressure [Safety of Mitocell]

Changes in blood pressure during the study , measured as systolic and diastolic blood pressure (in mmHg)

Changes in vital signs: pulse rate [Safety of Mitocell]

Changes in pulse rate during the study (in beats per minute)

Changes in vital signs: body temperature [Safety of Mitocell]

Changes in body temperature during the study (in degrees celsius)

Changes in clinical laboratory safety screen: haematology - hemoglobin [Safety of Mitocell]

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: Platelet count [Safety of Mitocell]

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: white blood cell (WBC) counts [Safety of Mitocell]

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: International Normalized Ratio (INR) [Safety of Mitocell]

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"

Changes in clinical laboratory safety screen: activated partial thromboplastin time (aPTT) [Safety of Mitocell]

Changes in laboratory variables for haematology: aPTT (sec) . Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance"

Electrocardiogram (ECG)

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)

Safety of Mitocell will be assessed by any clinically significant abnormalities on MRI scans as compared to Baseline.

Secondary Outcome Measures

MDS-UPDRS (Movement Disorder Society unified Parkinson's disease rating scale)

Change in MDS-UPDRS motor (Part III) "OFF" score compared to the baseline. All items have 5 response options with uniform anchors of: 0 = normal, 1 = slight (symptoms/signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/signs of frequency or intensity sufficient to cause a modest impact on function, 3 = moderate (symptoms/signs sufficiently frequent or intense to impact considerably, but not prevent function), 4 = severe (symptoms/signs that prevent function).

Modified Hoehn & Yahr staging

Change in Modified Hoehn & Yahr staging compared to the baseline.

18F-DOPA PET

Degree of radiotracer uptake increment/decrement shown on striatum of 18F-DOPA PET compared to the baseline.

levodopa equivalent daily dose (LEDD)

Reduction of Parkinson's medications consumption by calculating levodopa equivalent daily dose (LEDD) compared to the baseline.

PDQ-39 (Parkinson's Disease Questionnaire)

Change in PDQ-39 scale compared to the baseline. The PDQ-39 is a 39 questions Parkinson's Disease self-completed questionnaire that comprises 8 domains: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). All items are assumed to impact QoL and must be answered to compute scores for each dimension. Questions are answered based on experiences from the preceding month using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.

Beck Depression Inventory (BDI-II) scores

Net change from baseline in BDI-II scores. BDI-II Scale is a 21-item self-reported questionnaire which measures the existence and severity of symptoms of depression. Each of the 21 items on BDI-II tool represents a depressive symptom. The symptoms are each scored on a 4-point Likert scale of 0 to 3 (0=symptom is absent; 3=symptom is severe). Scores for each symptom are added up to obtain the total scores for all 21 items. Total score ranges from 0-63; of which 0-8 is considered no depression, 0-13 is minimal depression, 14-19 is mild depression, 20-28 is moderate depression and 29-63 is severe depression.

Hamilton Depression Rating Scale (HAM-D-17) scores

Net change from baseline in HAM-D-17 scores. The HAMD-17 is a 17-item assessment used to assess the severity of depression and its improvement during the course of therapy. Each item was evaluated and scored using either a 5-point scale of 0 (not present/absent) to 4 (very severe) or a 3-point scale of 0 (not present/absent) to 2 (marked). Higher scores indicate greater symptom severity. The total score was the sum of the scores from HAMD-17 Items 1 through 17 and ranged from 0 (not at all depressed) to 52 (severely depressed).

Mini Mental State Examination (MMSE) Scores

Net change from baseline in MMSE scores. The MMSE uses a 30 point questionnaire to measure cognitive impairment. The MMSE is scored from 0 to 30,with a score equal to or greater than 24 points indicating normal cognition, a score of 19-23 points indicating mild cognitive impairment, 10-18 points indicating moderate impairment and a score equal to or below 9 indicating severe impairment.

Full Information

NCT ID

NCT05094011

First Posted

July 20, 2021

Last Updated

April 20, 2023

Sponsor

Taiwan Mitochondrion Applied Technology Co., Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT05094011

Brief Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

March 1, 2024 (Anticipated)

Primary Completion Date

September 30, 2025 (Anticipated)

Study Completion Date

July 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Taiwan Mitochondrion Applied Technology Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Idiopathic Parkinson's Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

This study plans to enroll approximately 4 subjects to obtain 3 evaluable subjects successfully receiving 3×10^7 cells/hemisphere (total 6×10^7 cells, Cohort 1) and approximately 8 subjects to obtain 6 evaluable subjects for 1×10^8 cells/hemisphere (total 2×10^8 cells, Cohort 2)

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Single Arm Study

Arm Type

Experimental

Arm Description

Autologous MitoCell Transplantation in Subjects with Idiopathic Parkinson's Disease

Intervention Type

Biological

Intervention Name(s)

Aadipose-Derived Mesenchymal Stem Cells

Other Intervention Name(s)

MitoCell

Intervention Description

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 Measure Information:

Title

Grading of Adverse Events

Description

Grading will be assessed using NCI CTCAE, version 5.0.

Time Frame