A Safety and Tolerability Study of Neural Stem Cells (NR1) in Subjects With Chronic Ischemic Subcortical Stroke (ISS)

Study Overview
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Brief Summary
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Evaluation of the safety and tolerability of escalating doses of NR1 administered intracerebrally at a single time-point post-injury to subjects with chronic ISS with or without cortical stroke.

Detailed Description
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Evaluation of the safety and tolerability of escalating doses of NR1 administered intracerebrally at a single time-point post-injury to subjects with chronic ISS with or without cortical stroke. The study will be a dose escalation using up to 4 cohorts each at a single dose level, of intracerebral administration of NR1 cells. Secondary objectives are to evaluate clinical and radiologic responses as well as utility of efficacy measurement tools.

Official Title
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A Phase 1/Phase 2a Safety and Tolerability Study of Intracerebral Transplantation of Neural Stem Cells (NR1) in Subjects With Chronic Ischemic Subcortical Stroke (ISS) and Early Evaluation of Potentially Useful Efficacy Parameters

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Biological: Neural Stem Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 - 75 years History of ischemic subcortical stroke in the middle cerebral artery and/or lenticulostriate artery 6 to 60 months from time of stroke Ability of subject to understand and provide written Informed Consent Willing to take tacrolimus (Prograf) 2 days before and for 2 months after transplant Exclusion Criteria: Stroke lesion less than 1 cubic centimeter or greater than 100 cubic centimeters measured by MRI Index stroke is lacunar infarct less than 1 year old History or presence of any major neurological disease History of active cancer other than basal or squamous cell skin cancers History of seizures Pregnant or breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Neural Stem cells injected intracerebrally<br>Subject cohorts will be treated with increasing doses of Neural Stem Cells injected intracerebrally using a traditional 3+3 trial design | Biological: Neural Stem Cells<br>* NR1 is a human embryonic stem cell (hESC) derived product for the treatment of chronic ischemic subcortical stroke<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | 0-12 months | 
| Fugl Meyer (FM) motor score | Change in neurologic functional outcome to evaluate efficacy post-injection as defined by change in Fugl Meyer motor score in comparison to baseline | 0-12 months |