Clinical trial NCT02448641: Study of Modified Stem Cells (SB623) in Patients With Chronic Motor Deficit From Ischemic Stroke
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Ischemic Stroke
Keywords: ischemic stroke
chronic stroke
fixed motor deficits
Lead sponsor: SanBio, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Sumitomo Pharma America, Inc.
First posted: 2015-05-19
Enrollment: 163
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Subjects Whose Fugl-Meyer Motor Total Score (FMMS) Improved by ≥ 10 Points at Month 6 From Baseline
timeFrame: 6 months
Secondary outcomes:
measure: Modified Rankin Scale Response: The Proportion of Subjects That Improved at Least One Point on the mRS From Baseline
timeFrame: 6 months
measure: The Proportion of Subjects That Improved at Least 6 Points From Baseline on the ARAT Total Score at the Affected Side
timeFrame: 6 months
measure: The Proportion of Subjects That Improved at Least 1 Functional Level From Baseline on Gait Velocity
timeFrame: 6 months
measure: Neurological Quality of Life Response: T-scores of the Change From Baseline in the 2 Sub-domains (Upper Extremity Function and Lower Extremity Function)
timeFrame: 6 Months
measure: Global Rating of Perceived Change (GRPC): The Proportion of Subjects Scoring Either 7 or 6 on the Global Rating of Perceived Change by Both Subject and Clinician
timeFrame: 6 Months (LOCF)
Other outcomes:
measure: Additional Analysis (MMRM), Fugl-Meyer Motor Scale (FMMS)
timeFrame: 6 Months
measure: Proportion of Subjects Whose FMMS Motor Total Score Improve by ≥10 Points at Month 6 From Baseline (Per Protocol Population)
timeFrame: Month 6
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (Surgical/Assessment)
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Xenoscience, Inc. (Assessment)
state: Arizona
city: Carlsbad
country: United States
facility: The Research Center of Southern California (Assessment)
state: California
city: Downey
country: United States
facility: Rancho Los Amigos National Rehab Center
state: California
city: Fresno
country: United States
facility: Neuro-Pain Medical Center (Assessment)
state: California
city: Fresno
country: United States
facility: Neuro Pain Medical Center
state: California
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center (Assessment/Surgical)
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Orange
country: United States
facility: University of California Irvine (Assessment)
state: California
city: Placentia
country: United States
facility: Westview Clinical Research (Assessment)
state: California
city: Santa Monica
country: United States
facility: Providence Saint John's Health Center (Assessment)
state: California
city: Santa Monica
country: United States
facility: Providence St. John's Health Center (Surgical)
state: California
city: Santa Monica
country: United States
facility: Providence St. Johns Health Center
state: California
city: Stanford
country: United States
facility: Stanford Health Care (Surgical/Assessment)
state: California
city: Stamford
country: United States
facility: New England Institute for Clinical Research (Assessment)
state: Connecticut
city: Washington
country: United States
facility: MedStar National Rehabilitation Hospital (Assessment)
state: District of Columbia
city: Miami
country: United States
facility: University of Miami Miller School of Medicine (Assessment/Surgical)
state: Florida
city: Miami
country: United States
facility: University of Miami Jackson Memorial Hospital
state: Florida
city: Panama City
country: United States
facility: NeuroMedical Research Institute (Assessment)
state: Florida
city: Port Charlotte
country: United States
facility: Medsol Clinical Research Center (Assessment)
state: Florida
city: Port Charlotte
country: United States
facility: Neurostudies, Inc. (Assessment)
state: Florida
city: Tampa
country: United States
facility: University of South Florida (Assessment)
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital (Assessment)
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital (Surgical)
state: Georgia
city: Gainesville
country: United States
facility: Center for Advanced Research and Education (Assessment)
state: Georgia
city: Chicago
country: United States
facility: Northwestern Memorial Hospital (Surgical)
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center (Assessment)
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center (Surgical)
state: Illinois
city: Chicago
country: United States
facility: Rehabilitation Institute of Chicago
state: Illinois
city: Northbrook
country: United States
facility: Consultants in Neurology, Ltd. (Assessment)
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Healthcare System (Assessment)
state: Illinois
city: Elkhart
country: United States
facility: Indiana Medical Research, Elkhart Clinic (Assessment)
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center (Surgical)
state: Kansas
city: Overland Park
country: United States
facility: Kansas Institute of Research (Assessment)
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Hospital (Surgical)
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Clinical Trials Unit (Assessment)
state: Kentucky
city: Alexandria
country: United States
facility: NeuroMedical Clinic of Central Louisiana (Assessment)
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (Surgical)
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University (Assessment)
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System (Assessment)
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Newark
country: United States
facility: Rutgers New Jersey Medical School (Assessment)
state: New Jersey
city: New York
country: United States
facility: New York University Langone Medical Center (Surgical/Assessment)
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: White Plains
country: United States
facility: The Burke Rehabilitation Hospital (Assessment)
state: New York
city: Charlotte
country: United States
facility: Carolinas Rehabilitation (Assessment)
state: North Carolina
city: Akron
country: United States
facility: Neurology and Neuroscience Associates, Inc. (Assessment)
state: Ohio
city: Akron
country: United States
facility: Neurology and Neuroscience Associates
state: Ohio
city: Cleveland
country: United States
facility: University Hospital Case Medical Center (Surgical)
state: Ohio
city: Toledo
country: United States
facility: University of Toledo Medical Center (Assessment)
state: Ohio
city: Elkins Park
country: United States
facility: Moss Rehab (Assessment)
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania (Assessment)
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Hospital (Surgical)
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Comprehensive Stroke Center (Assessment)
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (Surgical/Assessment))
state: Pennsylvania
city: Willow Grove
country: United States
facility: Abington Neurological Associates (Assessment)
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (Surgical)
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Center for Neurologic Research (Assessment)
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Medical School
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston (Assessment/Surgical)
state: Texas
city: Morgantown
country: United States
facility: West Virginia University Hospitals (Assessment)
state: West Virginia
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
Study officials:
affiliation: Stanford Hospital and Clinics, School of Medicine
name: Gary Steinberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: