Phase 1 Safety and Tolerability Study of MSK-DA01 Cell Therapy for Advanced Parkinson's Disease

Study Overview
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Brief Summary
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This clinical trial is designed to test whether surgically injecting nerve cells that make dopamine into the brain of Parkinson's disease patients is safe, and to monitor for potential side effects.

Detailed Description
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Subjects will undergo surgical transplantation of the dopamine-producing cells under general anesthesia into a part of the brain called the putamen. Subjects then take medicines to partially suppress their immune system (aimed to prevent the body from rejecting the cells) for 1 year. Safety, tolerability, evidence of cell survival (using MRI and PET scans of the brain), and effect on Parkinson's disease symptoms are assessed for 2 years post-transplant.

Official Title
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Phase 1 Study To Assess the Safety and Tolerability of Human Embryonic Stem Cell-Derived Midbrain Dopamine Neuron Cell Therapy (MSK-DA01) For Advanced Parkinson's Disease

Conditions
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Advanced Parkinson's Disease

Intervention / Treatment
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* Biological: MSK-DA01
* Device: MSK-DA01 Cell Delivery Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 50-78 years old (Canada) Age 60-78 years old (United States) Diagnosis of Parkinson's Disease made between 3 to 20 years ago Taking levodopa, but with complications of therapy such as wearing off and/or dyskinesia Able to participate in all study visits and evaluations, including brain MRI and PET scan Existence of a study partner who may act as potential surrogate over long term for ongoing consent Exclusion Criteria: Diagnosis of primary mitochondrial disorder, epilepsy, stroke, multiple sclerosis or other neurodegenerative diseases such as Alzheimer's disease Prior Deep Brain Stimulation , lesion therapy, or gene therapy for PD Prior surgical or radiation therapy to the brain or spinal cord Any medical condition resulting in high risk of immunosuppressive drugs, including any active infectious disease Inability to temporarily stop anti-platelet agents or other anti-coagulant medications without serious risk Previous or currently active malignant disease within the past 5 years, except basal cell carcinoma or in situ uterine cervical carcinoma that have been treated Severe obesity (>350 lbs) or any condition that prevents use of PET/MRI Pregnancy or breastfeeding Contraindication to surgery or general anesthesia In the opinion of the investigator, any other condition regarded as making subject unsuitable for trial

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 78 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSK-DA01<br> | Biological: MSK-DA01<br>* MSK-DA01 is an experimental product derived from human embryonic stem cells. The stem cells were converted into brain cells that produce dopamine.<br>Device: MSK-DA01 Cell Delivery Device<br>* A device that is used for injection of fluids into the brain will be used. Some minor modifications have been made to the device to allow delivery of MSK-DA01 cells.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | The incidence of Serious Adverse Events (SAEs) at 1 year post-transplant. or abnormal tissue overgrowth related to presence of transplanted cells; | Baseline to 1 Year Post-Transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence of Cell Survival | Change in 18F-DOPA uptake using positron emission tomography (PET) from baseline to 1 and 2 years | Baseline to 1 Year Post-Transplant and Baseline to 2 Years Post-Transplant | 
| Changes in Motor Function | Changes in MDS-Unified Parkinson's Disease Rating Scale (UPDRS) motor sub-score in the off state from baseline to 2 years post-transplant. | Baseline to 1 Year Post-Transplant and Baseline to 2 Years Post-Transplant | 
| Changes in Waking Hours in Off State | Changes in number of waking hours in the off state from baseline to 2 years post-transplant. | Baseline to 1 Year Post-Transplant and Baseline to 2 Years Post-Transplant | 
| Continued Safety and Tolerability | Incidence of SAEs at 2 years post-transplant and incidence and type of AEs at 1 and 2 years post-transplant. | Baseline to 1 Year Post-Transplant and Baseline to 2 Years Post-Transplant |