Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT02448641
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02448641
Recruitment Status : Completed
First Posted : May 19, 2015
Results First Posted : April 17, 2020
Last Update Posted : October 8, 2020
Sponsor:
Collaborator:
Sunovion
Information provided by (Responsible Party):
SanBio, Inc.

Tracking Information
First Submitted Date  ICMJE May 15, 2015
First Posted Date  ICMJE May 19, 2015
Results First Submitted Date  ICMJE December 20, 2019
Results First Posted Date  ICMJE April 17, 2020
Last Update Posted Date October 8, 2020
Actual Study Start Date  ICMJE March 8, 2016
Actual Primary Completion Date December 5, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2020)
Proportion of Subjects Whose Fugl-Meyer Motor Total Score (FMMS) Improved by ≥ 10 Points at Month 6 From Baseline [ Time Frame: 6 months ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: May 18, 2015)
Proportion of subjects whose Fugl-Meyer Motor scale (FMMS) improve by ≥10 points at Month 6 from Baseline [ Time Frame: Month 6 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2020)
  • Modified Rankin Scale Response: The Proportion of Subjects That Improved at Least One Point on the mRS From Baseline [ Time Frame: 6 months ]
    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.
  • The Proportion of Subjects That Improved at Least 6 Points From Baseline on the ARAT Total Score at the Affected Side [ Time Frame: 6 months ]
    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.
  • The Proportion of Subjects That Improved at Least 1 Functional Level From Baseline on Gait Velocity [ Time Frame: 6 months ]
    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
  • Neurological Quality of Life Response: T-scores of the Change From Baseline in the 2 Sub-domains (Upper Extremity Function and Lower Extremity Function) [ Time Frame: 6 Months ]
    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.
  • 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 [ Time Frame: 6 Months (LOCF) ]
    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)
Original Secondary Outcome Measures  ICMJE
 (submitted: May 18, 2015)
  • Proportion of subjects whose Modified Rankin Scale (mRS) improve by ≥1 point at Month 6 from Baseline [ Time Frame: Month 6 ]
  • Proportion of subjects whose Action Research Arm Test (ARAT) improve by ≥6 points [ Time Frame: Month 6 ]
  • Proportion of subjects whose Gait Velocity on standard 10 m walk improve at least one 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]) at Month 6 from Baseline [ Time Frame: Month 6 ]
  • Mean change in T scores at Month 6 of NeuroQOL sub-domains Upper Extremity Function (Fine motor ADL) Lower Extremity Function (Mobility) [ Time Frame: Month 6 ]
  • Proportion of subjects scoring 7 (much better) or 6 (a little improved) in the Global Rating of Perceived Change scores at Month 6 assessed by subject (may be completed by caregiver) and by clinician [ Time Frame: Month 6 ]
  • All adverse events whether or not related to SB623 or surgical procedure using WHO toxicity criteria [ Time Frame: Month 12 ]
  • Adverse changes imaged by head MRI [ Time Frame: Month 12 ]
  • Serious adverse events (SAEs) using WHO toxicity criteria [ Time Frame: Month 12 ]
  • Serum chemistry hematology, vital signs, physical examinations [ Time Frame: Month 12 ]
  • Changes in serum antibodies to SB623 over time [ Time Frame: Month 12 ]
Current Other Pre-specified Outcome Measures
 (submitted: September 14, 2020)
  • Additional Analysis (MMRM), Fugl-Meyer Motor Scale (FMMS) [ Time Frame: 6 Months ]
    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.
  • Proportion of Subjects Whose FMMS Motor Total Score Improve by ≥10 Points at Month 6 From Baseline (Per Protocol Population) [ Time Frame: Month 6 ]
    Responders: subjects whose FMMS motor total score improve by ≥10 points at Month 6 from Baseline
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Modified Stem Cells (SB623) in Patients With Chronic Motor Deficit From Ischemic Stroke
Official Title  ICMJE 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
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Chronic Ischemic Stroke
Intervention  ICMJE
  • Biological: SB623 Implant (2.5M)
    2.5 million SB623 cells
  • Biological: SB623 Implant (5.0M)
    5 million SB623 cells
  • Procedure: Sham surgery
Study Arms  ICMJE
  • Experimental: SB623 Implant (2.5M)
    2.5 million SB623 cells
    Intervention: Biological: SB623 Implant (2.5M)
  • Experimental: SB623 Implant (5.0M)
    5 million SB623 cells
    Intervention: Biological: SB623 Implant (5.0M)
  • Sham Comparator: Sham Control
    Sham surgery
    Intervention: Procedure: Sham surgery
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 14, 2020)
163
Original Estimated Enrollment  ICMJE
 (submitted: May 18, 2015)
156
Actual Study Completion Date  ICMJE December 5, 2018
Actual Primary Completion Date December 5, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02448641
Other Study ID Numbers  ICMJE SB-STR02
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party SanBio, Inc.
Study Sponsor  ICMJE SanBio, Inc.
Collaborators  ICMJE Sunovion
Investigators  ICMJE
Principal Investigator: Gary Steinberg, MD, PhD Stanford Hospital and Clinics, School of Medicine
PRS Account SanBio, Inc.
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP