A Study of NCS-01 in Patients With Acute Ischemic Stroke

Study Overview
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Brief Summary
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This is an initial Phase1/2 dose-finding, randomized, multi-center study to evaluate the safety and tolerability of NCS-01 in patients with acute ischemic stroke. All patients will be randomized within 48 hours of stroke onset. This study will be conducted in 2 stages.

Official Title
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A Phase 1/2 Randomized Study to Evaluate the Safety and Tolerability of Intracarotid Artery Administration of NCS-01 in Patients With Acute Ischemic Stroke

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Biological: NCS-01


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, age 18 to 85 years inclusive Clinical evidence of acute ischemic unilateral cerebral infarction - Evidence of neurologic deficits as defined by NIHSS 6 to 18 or NIHSS < 6 with Fugl-Meyer upper extremity subtotal 6 to 40 inclusive Women of child bearing potential who agrees to take acceptable birth control as described in the ICF Provide written informed consent before participation, either by patient or a legal representative Exclusion Criteria: Progressive neurologic deficit An inability to undergo an MRI scan Any malignancies within the last 5 years Previous organ transplantation Participation in another clinical trial with an investigational drug, device or biologic within the preceding 3 months Women of childbearing potential with a positive pregnancy test Already dependent in activities of daily living (Rankin scale 3 or more) before the present acute stroke Known hypersensitivity, allergy or intolerance to the similar biologic interventions Any other clinically relevant acute or chronic diseases which could interfere with patients' safety during the trial, or expose them to undue risk, or which could interfere with study objectives judged by Investigator based on medical history, physical examination, laboratory tests and/or ECG

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NCS-01<br>human bone marrow derived cells | Biological: NCS-01<br>* single infusion<br>|
| Sham Comparator: sham<br>sham procedure | Biological: NCS-01<br>* single infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events -Safety by Incidence of Treatment-Emergent Adverse Events | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 . Incidence and nature of adverse events; vital signs; | multiple times for the duration of the study (baseline through Month 12) | 
| National Institutes of Health Stroke Scale (NIHSS) | Change from baseline in the NIHSS NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. The score for each ability is a number between 0 and 4, 0 being normal functioning and 4 being completely impaired. The patient's NIHSS score is calculated by adding the number for each element of the scale; 42 is the highest score possible. In the NIHSS, the higher the score, the more impaired a stroke patient is. | 1 hour, 3 hours, and 6 hours post infusion | 
| Number of participants with change in in physical examination | physical examination changes General appearance ,Head, eyes, ears, nose, and throat, Respiratory, Cardiovascular, Musculoskeletal, Abdomen, Neurologic, Extremities, Dermatologic, Lymphatic) | multiple times from baseline through Month 12 | 
| Number of participants with change in Electrocardiography (ECG) | ECG (standard digital 12-lead in singlicate) | multiple times for the duration of the study (baseline through Month 12) | 
| Number of participants with change in clinical laboratory evaluations | changes in clinical laboratory evaluations (Creatinine, Potassium(K+),Sodium (Na+) , Chloride (Cl-), Magnesium (Mg++), Calcium, Inorganic phosphate, Glucose, Urea,Bilirubin (Total) ,Bilirubin (direct), AST, ALT, GGT, Alkaline phosphatase, Total Protein Albumin, | multiple times for the duration of the study (baseline through Month 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with change in Modified Rankin Scale (mRS) | The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke.Score Description 0 No symptoms at all No significant disability despite symptoms; able to carry out all usual duties and activities Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance Moderate disability; requiring some help, but able to walk without assistance Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance Severe disability; bedridden, incontinent and requiring constant nursing care and attention Dead | multiple times for the duration of the study (baseline through Month 12) | 
| Number of participants with change in Cytokine panel (IL-1, 6, 8, etc.) | blood test for proteins that modulate the inflammatory response | multiple times for the duration of the study (baseline through Month 12) | 
| Number of participants with change in MRI | global white matter and grey matter volumetrics; cortical thinning on MRI | multiple times for the duration of the study (baseline through Month 12) | 
| Number of participants with change in Barthel Index | Barthel Index is a 4 point scale of Activities of Daily Living | multiple times for the duration of the study (baseline through Month 12) |