Study of Modified Stem Cells (SB623) in Patients With Chronic Motor Deficit From Ischemic Stroke

A Double-Blind, Controlled Phase 2b Study of the Safety and Efficacy of Modified Stem Cells (SB623) in Patients With Chronic Motor Deficit From Ischemic Stroke

Controlled study of stereotactic, intracranial injection of SB623 cells in patients with fixed motor deficits from ischemic stroke

This is a double-blind, sham-surgery controlled study of stereotactic, intracranial injection of SB623 cells in patients with fixed motor deficits from ischemic stroke. The study will be conducted at approximately 65 sites in the United States.

Two cohorts, Group 1 (2.5 and 5 million SB623 cells combined) and Group 2 (sham placebo), will be included in this study. Subjects who are randomized into this study will receive either 2.5 million SB623 cells, 5 million SB623 cells or sham surgery at a 1:1:1 randomization ratio. Randomization will be performed via an interactive web/voice response system (IXRS), stratified by Screening mRS score (recorded in the IXRS at the clinical site).

Inclusion Criteria:

1. Age 18-75 years, inclusive
2. Documented history of completed ischemic stroke in subcortical region of MCA or lenticulostriate artery with or without cortical involvement, with correlated findings by MRI
3. Between 6 and 90 months (7.5 years) post-stroke, and having a chronic motor neurological deficit
4. Neurological motor deficit substantially due to incident stroke
5. Modified Rankin Score of 2-4
6. Require Motricity Index 30-75 (UE Scale) or 27-74 (LE Scale)
7. Able to undergo all planned neurological assessments
8. Able and willing to undergo magneti resonance imaging (MRI) with contrast and computed tomography (CT)
9. Agree that use of antiplatelet, anti-coagulant, or non-steroidal anti-inflammatory drugs to be determined by the local medical staff and in accordance with the ACCP 2012 guideline "Perioperative Management of Antithrombotic Therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th Edition: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines", if applicable , provided that no antiplatelet, anti-coagulant, or non-steroidal anti-inflammatory drugs are to be restarted post-surgery until after the Day 8 MRI is read and are determined to be safe to re-start
10. Subjects must have had physical therapy prior to entry (and be willing to continue to the extent possible)
11. Must be willing to discontinue herbal or non-traditional medicines for 1 week before and 1 week after the surgical procedure and be willing to continue to the extent possible
12. Ability of patient or legal authorized representative to understand and sign an Informed Consent

Exclusion Criteria:

1. History or presence of any other major neurological disease other than stroke
2. Cerebral infarct size >150 cm3 measured by MRI
3. Primary intracerebral hemorrhage
4. Myocardial infarction within prior 6 mos.
5. Malignancy unless in remission >5 yrs.
6. Clinically significant finding on MRI of brain not related to stroke
7. Any seizures in the 3 months prior to Screening
8. More than 5 degrees of contracture at shoulder, elbow, wrist, fingers, hip, knee and ankle
9. Other neurologic, neuromuscular or orthopedic disease that limits motor function
10. Uncontrolled systemic illness, including, but not limited to: hypertension; diabetes; renal, hepatic, or cardiac failure
11. Positive findings on tests for occult malignancy, unless a non-malignant etiology is confirmed
12. Uncontrolled major psychiatric illness, including depression symptoms (CESD R Scale of ≥16 is exclusionary)
13. Total bilirubin >1.9 mg/dL at Screening
14. Serum creatinine >1.5 mg/dL at Screening
15. Hemoglobin <10.0 g/dL at Screening
16. Absolute neutrophil count <2000 /mm3 at Screening
17. Absolute lymphocytes <800 /mm3 at Screening
18. Platelet count <100,000 /mm3 at Screening
19. Liver disease supported by AST (SGOT) or ALT (SGPT) ≥2.5 x upper limit of normal at Screening
20. Serum calcium >11.5 mg/dL at Screening
21. International Normalized Ratio of Prothrombin Time (INR) >1.2 at Screening if the patient does not take anticoagulants; for patients on anticoagulants, INR must be confirmed to be ≤1.2 prior to surgery
22. Presence of craniectomy or other contraindication to stereotactic surgery
23. Participation in any other investigational trial within 4 weeks of initial screening and within 7 weeks of Baseline visit
24. Botulinum toxin injection, phenol injection, intrathecal baclofen, or any other interventional treatments for spasticity (except bracing and splinting) 16 weeks prior to the Baseline visit
25. Substance use disorder (per DSM-V criteria, including drug or alcohol)
26. Contraindications to head MRI (with constrast) or CT
27. Pregnant or lactating
28. Female patients of childbearing potential unwilling to use an adequate birth control method during the 12 months of the study
29. Any other condition or situation that the investigator believes may interfere with the safety of the subject or the intent and conduct of the study
30. Any prior SB623 cell implantation and/or any prior stem cell treatment for stroke or other reason regardless of mode of administration