A Study of Modified Stem Cells in Stable Ischemic Stroke

Study Overview
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Brief Summary
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The primary purpose of the clinical study is to determine the safety of a modified stem cell SB623 when administered to chronic, stable ischemic stroke patients. A second purpose is to determine whether SB623 might improve stroke symptoms. Chronic, stable ischemic stroke patients must be between 6 and 60 months after their stroke, and with only this one prior stroke, and with no further improvement from physical therapy.

Detailed Description
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Chronic, stable stroke patients have no existing alternative treatments after rehabilitation therapy. SB623, a modified stem cell preparation, has been shown to improve motor function when administered in animal models of stable stroke. Safety studies in animals have shown no adverse events attributed to SB623. Patients who meet the entry criteria for this study will have regular examinations, radiological evaluations (CT, MRI, PET), and be followed for two years. Regular neurological evaluations will also be done using standard questionnaires, with occasional video recording if improvements are evident. Key entry criteria for this study, in addition to 6-60 months post-ischemic stroke, include moderately severe symptoms--e.g., difficulty standing or walking, and/or difficulty using arms or hands, and/or speech impediments.

Official Title
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A Phase 1/2A Study of the Safety and Efficacy of Modified Stromal Cells (SB623) in Patients With Stable Ischemic Stroke

Conditions
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Chronic Ischemic Stroke

Intervention / Treatment
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* Biological: SB623


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented history of one completed ischemic stroke in subcortical region of MCA or lenticulostriate artery with or without cortical involvement Between 6 and 60 months post-stroke, and having a motor neurological deficit No significant further improvement with physical therapy/rehabilitation Able and willing to undergo computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET) scans of the head Exclusion Criteria: History of more than 1 symptomatic stroke History of seizures History or presence of any other major neurological disease Myocardial infarction within prior 6 mos. Known presence of any malignancy except squamous or basal cell carcinoma of the skin Participation in any other investigational trial within 4 weeks of initial screening and within 7 weeks of study entry Contraindications to head CT, MRI, or PET Pregnant or lactating

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SB623 Implant (2.5M)<br>2.5 million SB623 cells | Biological: SB623<br>* SB623, a modified stem-cell product<br>|
| Experimental: SB623 Implant (5.0M)<br>5 million SB623 cells | Biological: SB623<br>* SB623, a modified stem-cell product<br>|
| Experimental: SB623 Implant (10.0M)<br>10 million SB623 cells | Biological: SB623<br>* SB623, a modified stem-cell product<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | Number of subjects with TEAEs by maximum severity. The severity of all AEs was assessed by the Investigator using the World Health Organization (WHO) Toxicity Scale. For abnormalities not found elsewhere in the WHO table, the following scale was used to assign severity: Mild: Transient mild discomfort; no limitation in activity; no medical intervention/therapy required. Moderate: Mild-to-moderate limitation in activity; some assistance may be need. No or minimal medical intervention/therapy required. Severe: Marked limitation in activity, some assistance usually required; medical intervention/therapy required; hospitalization or prolongation of current hospitalization possible. Life-threatening: Extreme limitation in activity, significant assistance required; significant medial intervention/therapy required; hospitalization or prolongation of current hospitalization or hospice care probable. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the European Stroke Scale (ESS) Total Score From Baseline at Month 6 | The ESS is the sum of 14 items that are used to assess a patient who has recently had a stroke. These 14 items are level of consciousness, comprehension, speech, visual field, gaze, facial movement, arm in outstretched position, arm raising, extension of the wrist, fingers, leg maintained in position, leg flexing, dorsiflexion of the foot, and gait. A certain number of points are given for each parameter. The range of the total score of ESS is 0 - 100, with a completely normal person having a score of 100 and maximally affected person with a score of zero. | 6 months | 
| Change in the European Stroke Scale (ESS) Motor Function Total Score From Baseline at Month 6 | The ESS motor function score is a sum of the selected items: facial movement, arm in outstretched position, arm raising, extension of wrist, fingers, leg maintained in position, leg flexing, dorsiflexion of foot, and gait. A completely normal person will have a score of 66. The maximally affected person will have a score of zero. | 6 months | 
| Change in the National Institutes of Health Stroke Scale (NIHSS) Total Score From Baseline at Month 6 | The NIHSS is a standardized method used to measure the level of impairment caused by a stroke. The scale consists of 11 items that measure several aspects of brain function, including consciousness, vision, sensation, movement, speech, and language. A certain number of points are given for each impairment uncovered during a focused neurological examination. A maximal score of 42 represents the most severe and devastating stroke with 0=no stroke, 1-4=minor stroke, 5-15=moderate stroke, 15-20=moderate/severe stroke, and 21-42=severe stroke. | 6 months | 
| Change in the National Institutes of Health Stroke Scale (NIHSS) Motor Function Total Score From Baseline at Month 6 | The NIHSS is a standardized method used to measure the level of impairment caused by a stroke. The NIHSS Motor Function Total Score consists of 3 items: motor arm, motor leg, and limb ataxia, with 0 = no stroke and a maximal score of 18 = most severe impairment for motor function. | 6 months | 
| Change in the Modified Rankin Scale (mRS) Response From Baseline at Month 6 | The mRS is a commonly used scale for measuring the degree of disability in daily activities for patients who have suffered a stroke. The mRS is an ordinal scale from 0 (no symptoms at all) to 5 (severe disability; requiring constant nursing care and attention, bedridden, incontinent) with a sixth category of death. | 6 months | 
| Change in the Fugl-Meyer Total Score From Baseline at Month 6 | The Fugl-Meyer Scale is a stroke-specific, performance-based impairment index. The scale is comprised of 5 domains (motor score, sensation, balance, joint range of motion, and joint pain) with 155 items in total. Scoring is based on direct observation of performance. Scale items in all 5 domains are scored on the basis of ability to complete the item using a 3-point Likert-type ordinal scale, where 0=cannot perform, 1=performs partially, and 2=performs fully. Points are divided among the domains: (a) Motor performance [0 (hemiplegia) - 100 (normal motor performance) points]; (b) Balance [0-14 points: 6 for sitting; 8 for standing]; (c) Sensation [0-24 points: 8 for light touch; 16 for position sense]; (d) Joint range of motion [0-44 points]; (e) Joint pain [0-44 points]. For all domains, a maximally affected person will score 0 while a fully functional person will have the highest score. All items are summed to provide a minimum score of 0 and a maximum score of 226. | 6 months | 
| Change in the Fugl-Meyer Motor Total Score (FMMS) Total Score From Baseline at Month 6 | The FMMS is used as a clinical measure of body function impairment after stroke that assesses several dimensions of motor impairment, including range of motion in upper and lower limbs, reflex activity, volitional movement, and coordination. The FMMS motor total score ranged from 0 (hemiplegia) to a maximum of 100 points (normal motor performance), and is comprised of a 33-item upper extremity subscale (UE-FMMS) and the 17-item lower extremity subscale (LE-FMMS). Items were scored on a 3-point ordinal scale: 0= cannot perform; 1= partial motion; 2= full motion Individual items are summed to determine scores for the 2 subscale scores, as well as a motor total score (total of the 2 subscales UE-FMMS and LE-FMMS). As a result, the UE-FMMS subscale score ranged from 0 to 66 and the LE-FMMS subscale score ranged from 0 to 34. A maximally affected person will have a score of 0 while a fully functional person will have the highest score (i.e., 34 for LE-FMMS, 66 for UE-FMMS, 100 for FMMS) | 6 months | 
| Change in the Fugl-Meyer Upper Extremity Motor Function Total Score From Baseline at Month 6 | The Fugl-Meyer Upper Extremity subscale (UE-FMMS) is comprised of 33 items that assess several dimensions of motor impairment, including range of motion in upper limbs, reflex activity, volitional movement, and coordination. Scoring is based on direct observation of performance and is scored using a 3-point ordinal scale, where 0=cannot perform; 1=partial motion; and 2=full motion Individual items are summed to provide ranging from 0 (minimum) to 66 (maximum). A maximally affected person will have a score of 0 while a fully functional person will a score of 66. | 6 months | 
| Change in the Fugl-Meyer Lower Extremity Motor Function Total Score From Baseline at Month 6 | The Fugl-Meyer Lower Extremity subscale (LE-FMMS) is comprised of 17 items that assess several dimensions of motor impairment, including range of motion in lower limbs, reflex activity, volitional movement, and coordination. Scoring is based on direct observation of performance and is scored using a 3-point ordinal scale, where 0=cannot perform; 1=partial motion; and 2=full motion Individual items are summed to provide ranging from 0 (minimum) to 34 (maximum). A maximally affected person will have a score of 0 while a fully functional person will a score of 34. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Stroke, Stable Stroke, Ischemic Stroke, Fixed Motor Deficits