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

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

Study Overview

• Status: Completed
• Conditions: Chronic Ischemic Stroke
• Intervention / Treatment: Biological: SB623 Implant (2.5M); Biological: SB623 Implant (5.0M); Procedure: Sham surgery

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).

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham (Surgical/Assessment)
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Xenoscience, Inc. (Assessment)
  • California
    • Carlsbad, California, United States, 92011
      • The Research Center of Southern California (Assessment)
    • Downey, California, United States, 90242
      • Rancho Los Amigos National Rehab Center
    • Fresno, California, United States, 93710
      • Neuro-Pain Medical Center (Assessment)
    • Fresno, California, United States, 95710
      • Neuro Pain Medical Center
    • Irvine, California, United States
      • University of California Irvine
    • Los Angeles, California, United States
      • UCLA Medical Center
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center (Assessment/Surgical)
    • Orange, California, United States, 92868
      • University of California Irvine (Assessment)
    • Placentia, California, United States, 92870
      • Westview Clinical Research (Assessment)
    • Santa Monica, California, United States, 90404
      • Providence Saint John's Health Center (Assessment)
    • Santa Monica, California, United States, 90404
      • Providence St. John's Health Center (Surgical)
    • Santa Monica, California, United States
      • Providence St. Johns Health Center
    • Stanford, California, United States, 94305
      • Stanford Health Care (Surgical/Assessment)
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • New England Institute for Clinical Research (Assessment)
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar National Rehabilitation Hospital (Assessment)
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine (Assessment/Surgical)
    • Miami, Florida, United States
      • University of Miami Jackson Memorial Hospital
    • Panama City, Florida, United States, 32405
      • NeuroMedical Research Institute (Assessment)
    • Port Charlotte, Florida, United States, 33952
      • Medsol Clinical Research Center (Assessment)
    • Port Charlotte, Florida, United States, 33952
      • Neurostudies, Inc. (Assessment)
    • Tampa, Florida, United States, 33606
      • University of South Florida (Assessment)
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Memorial Hospital (Assessment)
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital (Surgical)
    • Gainesville, Georgia, United States, 30501
      • Center for Advanced Research and Education (Assessment)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital (Surgical)
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center (Assessment)
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center (Surgical)
    • Chicago, Illinois, United States
      • Rehabilitation Institute of Chicago
    • Northbrook, Illinois, United States, 60062
      • Consultants in Neurology, Ltd. (Assessment)
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Healthcare System (Assessment)
  • Indiana
    • Elkhart, Indiana, United States, 46514
      • Indiana Medical Research, Elkhart Clinic (Assessment)
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center (Surgical)
    • Overland Park, Kansas, United States, 66211
      • Kansas Institute of Research (Assessment)
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Hospital (Surgical)
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Clinical Trials Unit (Assessment)
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • NeuroMedical Clinic of Central Louisiana (Assessment)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center (Surgical)
  • Michigan
    • Detroit, Michigan, United States
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48201
      • Wayne State University (Assessment)
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System (Assessment)
  • New Jersey
    • Newark, New Jersey, United States, 07013
      • Rutgers New Jersey Medical School (Assessment)
  • New York
    • New York, New York, United States, 10016
      • New York University Langone Medical Center (Surgical/Assessment)
    • New York, New York, United States
      • NYU Langone Medical Center
    • White Plains, New York, United States, 10605
      • The Burke Rehabilitation Hospital (Assessment)
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Rehabilitation (Assessment)
  • Ohio
    • Akron, Ohio, United States, 44320
      • Neurology and Neuroscience Associates
    • Akron, Ohio, United States, 44320
      • Neurology and Neuroscience Associates, Inc. (Assessment)
    • Cleveland, Ohio, United States, 44106
      • University Hospital Case Medical Center (Surgical)
    • Toledo, Ohio, United States, 43614
      • University of Toledo Medical Center (Assessment)
  • Pennsylvania
    • Elkins Park, Pennsylvania, United States, 19006
      • Moss Rehab (Assessment)
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania (Assessment)
    • Philadelphia, Pennsylvania, United States, 19106
      • Pennsylvania Hospital (Surgical)
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Comprehensive Stroke Center (Assessment)
    • Philadelphia, Pennsylvania, United States
      • Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center (Surgical/Assessment))
    • Willow Grove, Pennsylvania, United States, 19090
      • Abington Neurological Associates (Assessment)
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (Surgical)
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Chattanooga Center for Neurologic Research (Assessment)
  • Texas
    • Dallas, Texas, United States
      • University of Texas Medical School
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston (Assessment/Surgical)
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Hospitals (Assessment)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SB623 Implant (2.5M); 2.5 million SB623 cells	Biological: SB623 Implant (2.5M); 2.5 million SB623 cells
Experimental: SB623 Implant (5.0M); 5 million SB623 cells	Biological: SB623 Implant (5.0M); 5 million SB623 cells
Sham Comparator: Sham Control; Sham surgery	Procedure: Sham surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Whose Fugl-Meyer Motor Total Score (FMMS) Improved by ≥ 10 Points at Month 6 From Baseline	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 both upper and lower limbs, reflex activity, volitional movement, and co-ordination. The FMMS motor component consists of the 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 were then summed to determine scores for the 2 subscale scores, as well as a motor total score (total of all item scores including 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. The FMMS motor total score ranged from 0 (hemiplegia) to a maximum of 100 points (normal motor performance). Responders: subjects whose FMMS motor total score improve by ≥10 points at Month 6 from Baseline	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale Response: The Proportion of Subjects That Improved at Least One Point on the mRS From Baseline	Responders: The subjects that improved at least one point on the mRS from Baseline Modified Rankin Scale (mRS): This scale is used to measure the degree of disability or dependence in the daily activities of people who had 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
The Proportion of Subjects That Improved at Least 6 Points From Baseline on the ARAT Total Score at the Affected Side	Responders: The subjects that improved at least 6 points from Baseline on the ARAT total score at the affected side. Action Research Arm Test (ARAT): The test was scored for left and right side separately. Performance on each item was rated on a 4-point ordinal scale ranging from: 3 (performed test normally in less than 5 seconds); 2 (completed test, but took abnormally long or had great difficult, with time varying from 5 to 60 seconds; 1 (performed test partially); 0 (could perform no part of the test). The ARAT is a 19-item measure divided into 4 subtests: Grasp subscale (with 6 items and a score range of 0 to 18); Grip subscale with 4 items and a score range of 0 to 12); Pinch subscale with 6 items and a score range of 0 to 18); Gross arm movement subscale (with 3 items and a score range of 0 to 9). The maximum score on the ARAT is 57 points (possible range 0 to 57) for each side.	6 months
The Proportion of Subjects That Improved at Least 1 Functional Level From Baseline on Gait Velocity	Responders: The subjects that improved at least 1 functional level (eg, from < 0.4 m/s to 0.4-0.8 m/s or from 0.4-0.8 m/s to > 0.8 m/s) from Baseline on Gait Velocity. Gait Velocity was measured on a standard 10 meter walk. Two trials were tested and the average result from both was used for analysis	6 months
Neurological Quality of Life Response: T-scores of the Change From Baseline in the 2 Sub-domains (Upper Extremity Function and Lower Extremity Function)	The Neurological Quality of Life (NeuroQOL) was used as a measure of change in the levels of Quality of Life, Satisfaction and Participation, secondary to improvements in the subject's upper and lower extremity motor function. NeuroQOL is summation of item scores for upper extremity (8 terms: score 8 - 40) and lower extremity (8 items: score 8 - 40) separately. The item scores are on a 1 to 5 scale (1 = unable to do; 2 = with much difficulty; 3 = with some difficulty; 4 = with little difficulty; 5 = without any difficulty). The result provided here shows NeuroQOL score converted to T-score. The range for Upper extremity T-score and Lower extremity T-score are 12.8 to 53.8 and 16.5 to 58.6 respectively.	6 Months
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	Responders: Participants who scored either 7 [much better] or 6 [a little better, meaningful]) Global Rating of Perceived Change from Baseline: Subjects and Clinicians were asked about perceived changes in their motor function by comparing "how well they are doing compared to before the surgical procedure". The Subject Global Rating of Perceived Change was completed by the subject (or by the caregiver using the subject's answers). The following 7-point Likert scale was used: Score 7 (much better); Score 6 (a little better, meaningful); Score 5 (a little better, not meaningful); Score 4 (about the same); Score 3 (a little worse, not meaningful); Score 2 (a little worse, meaningful); Score 1 (much worse)	6 Months (LOCF)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional Analysis (MMRM), Fugl-Meyer Motor Scale (FMMS)	An additional analysis using mixed model for repeated measures (MMRM) was performed treating the change from Baseline in FMMS total score as a continuous outcome (dependent) variable. The independent variables were treatment, visit, treatment-by-visit interaction, and pooled surgical site as effects, and Baseline FMMS total score and Baseline mRS score as covariates. Least-squares means (LS-mean) with SE was calculated for the change from baseline measurements.	6 Months
Proportion of Subjects Whose FMMS Motor Total Score Improve by ≥10 Points at Month 6 From Baseline (Per Protocol Population)	Responders: subjects whose FMMS motor total score improve by ≥10 points at Month 6 from Baseline	Month 6

Collaborators and Investigators

• Sponsor: SanBio, Inc.
• Collaborators: Sunovion
• Investigators: Principal Investigator: Gary Steinberg, MD, PhD, Stanford Hospital and Clinics, School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2016
• Primary Completion (Actual): December 5, 2018
• Study Completion (Actual): December 5, 2018

Study Registration Dates

• First Submitted: May 15, 2015
• First Submitted That Met QC Criteria: May 18, 2015
• First Posted (Estimate): May 19, 2015

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: September 14, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: ischemic stroke; chronic stroke; fixed motor deficits
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: SB-STR02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided