To evaluate the safety and efficacy of transplantation of human induced pluripotent stem cell-derived dopaminergic progenitors, CT1-DAP001, into the corpus striatum in patients with Parkinson's disease
Single-center, open-label, uncontrolled. The primary objective of this study is to evaluate the safety of CT1-DAP001 in subjects with Parkinson's disease by determining the incidence and severity of adverse events, especially graft expansion, after transplantation into the corpus striatum. Other objectives are to evaluate the efficacy of CT1-DAP001 through the assessment of Parkinson's disease symptoms and clinical severity or progression.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
7
Investigational PET agents will be synthesized at UCSD and administered to subjects according to the local institutional guidelines. IND applications for these agents are linked with the IND application for the study product, CT1-DAP001. The IND applications for the PET radiopharmaceuticals contains the manufacturing method, specifications, quality testing, clinical usage, and safety and efficacy information for individual PET agents. Investigational Cell Injector Suniviion needle: The investigational instrument will be used to administer dopaminergic progenitors into the putamen. After aspirating cells, the instrument will be attached to a Leksell stereotactic frame to administer the cells into the brain.
University of California, San Diego
La Jolla, California, United States
RECRUITINGIncidence And Severity Of Adverse Events
For adverse events reported, the severity will be assessed, and the incidence in the treatment period will be determined.
Time frame: 24 months
ACCEPTABILITY
Assessed by presence or absence of graft expansion (\> 3 cm3) in the brain at 24 months after transplantation
Time frame: 24 months
Improvement or worsening of involuntary movements
Assessed by dyskinesia score, measured as the change in dyskinesia score from Baseline to each post-transplantation time point.
Time frame: 24 months
ACCURACY
Assessed by FDOPA (MRI) of tissue expansion The expansion on MRI will be assessed at each time point of measurement * day before transplantation, * immediately after transplantation, * day after transplantation, * 4 weeks, 12 weeks, 6 months, 18 months, (if clinically indicated) * 12 months, 24 months after transplantation
Time frame: 24 months
MDS-UPDRS Part III totalscore (at OFF time)
This endpoint is defined as the change in UPDRS Part III score at OFF time from Baseline to each post-transplantation time point. The efficacy will be assessed based on MDS-UPDRS Part III total score at OFF time at 24 months after cell transplantation. 1. Excellent response defined as a decrease of ≥ 5 2. Good response defined as a decrease of 0 to 4
Time frame: 24 months
MDS-UPDRS Part III totalscore (at ON time)
This endpoint is defined as the change in UPDRS Part III score at ON time from Baseline to each post-transplantation time point.
Time frame: 24 months
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Average daily ON duration (with or without dyskinesia) and OFF duration
This endpoint is defined as the change in daily ON duration (with or without dyskinesia) or OFF duration from Baseline to each post-transplantation time point.
Time frame: 24 months
L-dopa equivalent dose
This endpoint is defined as the change in L-dopa equivalent dose from Baseline to 4 weeks, 12 weeks, 6 months, 12 months, 18 months, or 24 months after transplantation. Formula to convert to the L-dopa dose: L-dopa 100 mg = pramipexole salt 1 mg = ropinirole 5 mg = rotigotine 7.5 mg = bromocriptine 10 mg = pergolide 1 mg = cabergoline 1.5 mg = selegiline 10 mg = amantadine 100 mg = apomorphine 10 mg
Time frame: 24 months