Chronic Ischemic Stroke
Conditions
Keywords
ischemic stroke, chronic stroke, fixed motor deficits
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).
Interventions
BIOLOGICALSB623 Implant (2.5M)
2.5 million SB623 cells
BIOLOGICALSB623 Implant (5.0M)
5 million SB623 cells
PROCEDURESham surgery
Sponsors
Sumitomo Pharma America, Inc.
SanBio, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Whose Fugl-Meyer Motor Total Score (FMMS) Improved by ≥ 10 Points at Month 6 From Baseline | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modified Rankin Scale Response: The Proportion of Subjects That Improved at Least One Point on the mRS From Baseline | 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 | 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 | 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) | 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 | 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) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Additional Analysis (MMRM), Fugl-Meyer Motor Scale (FMMS) | 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) | Month 6 | Responders: subjects whose FMMS motor total score improve by ≥10 points at Month 6 from Baseline |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SB623 Implant (2.5M) 2.5 million SB623 cells | 55 |
| SB623 Implant (5.0M) 5 million SB623 cells | 56 |
| Sham Control Control Group: Sham surgery | 52 |
| Total | 163 |
Baseline characteristics
| Characteristic | SB623 Implant (2.5M) | SB623 Implant (5.0M) | Sham Control | Total |
|---|---|---|---|---|
| Age, Continuous | 57.5 years STANDARD_DEVIATION 11.08 | 58.9 years STANDARD_DEVIATION 9.99 | 55.2 years STANDARD_DEVIATION 11.57 | 57.2 years STANDARD_DEVIATION 10.92 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 0 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 53 Participants | 52 Participants | 157 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 participants | 2 participants | 6 participants | 9 participants |
| Race/Ethnicity, Customized Black or African American | 6 participants | 1 participants | 2 participants | 9 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Other | 3 participants | 2 participants | 1 participants | 6 participants |
| Race/Ethnicity, Customized White | 45 participants | 51 participants | 42 participants | 138 participants |
| Region of Enrollment United States | 55 participants | 56 participants | 52 participants | 163 participants |
| Sex: Female, Male Female | 21 Participants | 20 Participants | 19 Participants | 60 Participants |
| Sex: Female, Male Male | 34 Participants | 36 Participants | 33 Participants | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 1 / 56 | 0 / 52 |
| other Total, other adverse events | 52 / 55 | 53 / 56 | 51 / 52 |
| serious Total, serious adverse events | 15 / 55 | 15 / 56 | 10 / 52 |
Outcome results
Primary
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
Time frame: 6 months
Population: Modified Intent-to-Treat (mITT) Population: Included all randomized subjects who completed the surgery treatment procedure. A total of 111 subjects received treatment with SB623; 55 subjects were randomized to receive 2.5 million SB623 cells and 56 subjects to receive 5 million SB623 cells.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SB623 Implant (2.5M) | Proportion of Subjects Whose Fugl-Meyer Motor Total Score (FMMS) Improved by ≥ 10 Points at Month 6 From Baseline | Non-responder | 46 Participants |
| SB623 Implant (2.5M) | Proportion of Subjects Whose Fugl-Meyer Motor Total Score (FMMS) Improved by ≥ 10 Points at Month 6 From Baseline | Responder | 7 Participants |
| SB623 Implant (2.5M) | Proportion of Subjects Whose Fugl-Meyer Motor Total Score (FMMS) Improved by ≥ 10 Points at Month 6 From Baseline | Unknown | 2 Participants |
| SB623 Implant (5.0M) | Proportion of Subjects Whose Fugl-Meyer Motor Total Score (FMMS) Improved by ≥ 10 Points at Month 6 From Baseline | Non-responder | 45 Participants |
| SB623 Implant (5.0M) | Proportion of Subjects Whose Fugl-Meyer Motor Total Score (FMMS) Improved by ≥ 10 Points at Month 6 From Baseline | Responder | 9 Participants |
| SB623 Implant (5.0M) | Proportion of Subjects Whose Fugl-Meyer Motor Total Score (FMMS) Improved by ≥ 10 Points at Month 6 From Baseline | Unknown | 2 Participants |
| Sham Control | Proportion of Subjects Whose Fugl-Meyer Motor Total Score (FMMS) Improved by ≥ 10 Points at Month 6 From Baseline | Responder | 7 Participants |
| Sham Control | Proportion of Subjects Whose Fugl-Meyer Motor Total Score (FMMS) Improved by ≥ 10 Points at Month 6 From Baseline | Unknown | 7 Participants |
| Sham Control | Proportion of Subjects Whose Fugl-Meyer Motor Total Score (FMMS) Improved by ≥ 10 Points at Month 6 From Baseline | Non-responder | 38 Participants |
Comparison: Combined SB623 Implant Vs Sham Surgery group at Month 6p-value: 0.674395% CI: [0.35, 5.09]Mixed Models Analysis
Secondary
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)
Time frame: 6 Months (LOCF)
Population: Modified Intent-to-Treat (mITT) Population: Included all randomized subjects who completed the surgery treatment procedure. A total of 111 subjects received treatment with SB623; 55 subjects were randomized to receive 2.5 million SB623 cells and 56 subjects to receive 5 million SB623 cells.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| SB623 Implant (2.5M) | 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 | As per Subject | Responder | 18 Participants |
| SB623 Implant (2.5M) | 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 | As per Clinician | Responder | 15 Participants |
| SB623 Implant (2.5M) | 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 | As per Clinician | Unknown | 1 Participants |
| SB623 Implant (2.5M) | 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 | As per Subject | Non-responder | 37 Participants |
| SB623 Implant (2.5M) | 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 | As per Clinician | Non-responder | 39 Participants |
| SB623 Implant (2.5M) | 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 | As per Subject | Unknown | 0 Participants |
| SB623 Implant (5.0M) | 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 | As per Clinician | Non-responder | 38 Participants |
| SB623 Implant (5.0M) | 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 | As per Clinician | Unknown | 0 Participants |
| SB623 Implant (5.0M) | 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 | As per Subject | Unknown | 0 Participants |
| SB623 Implant (5.0M) | 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 | As per Subject | Responder | 25 Participants |
| SB623 Implant (5.0M) | 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 | As per Subject | Non-responder | 31 Participants |
| SB623 Implant (5.0M) | 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 | As per Clinician | Responder | 18 Participants |
| Sham Control | 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 | As per Clinician | Responder | 13 Participants |
| Sham Control | 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 | As per Subject | Non-responder | 30 Participants |
| Sham Control | 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 | As per Subject | Unknown | 0 Participants |
| Sham Control | 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 | As per Subject | Responder | 22 Participants |
| Sham Control | 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 | As per Clinician | Non-responder | 39 Participants |
| Sham Control | 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 | As per Clinician | Unknown | 0 Participants |
Secondary
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.
Time frame: 6 months
Population: Modified Intent-to-Treat (mITT) Population: Included all randomized subjects who completed the surgery treatment procedure. A total of 111 subjects received treatment with SB623; 55 subjects were randomized to receive 2.5 million SB623 cells and 56 subjects to receive 5 million SB623 cells.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SB623 Implant (2.5M) | Modified Rankin Scale Response: The Proportion of Subjects That Improved at Least One Point on the mRS From Baseline | Non-responder | 43 Participants |
| SB623 Implant (2.5M) | Modified Rankin Scale Response: The Proportion of Subjects That Improved at Least One Point on the mRS From Baseline | Responder | 6 Participants |
| SB623 Implant (2.5M) | Modified Rankin Scale Response: The Proportion of Subjects That Improved at Least One Point on the mRS From Baseline | Unknown | 6 Participants |
| SB623 Implant (5.0M) | Modified Rankin Scale Response: The Proportion of Subjects That Improved at Least One Point on the mRS From Baseline | Non-responder | 42 Participants |
| SB623 Implant (5.0M) | Modified Rankin Scale Response: The Proportion of Subjects That Improved at Least One Point on the mRS From Baseline | Responder | 10 Participants |
| SB623 Implant (5.0M) | Modified Rankin Scale Response: The Proportion of Subjects That Improved at Least One Point on the mRS From Baseline | Unknown | 4 Participants |
| Sham Control | Modified Rankin Scale Response: The Proportion of Subjects That Improved at Least One Point on the mRS From Baseline | Responder | 9 Participants |
| Sham Control | Modified Rankin Scale Response: The Proportion of Subjects That Improved at Least One Point on the mRS From Baseline | Unknown | 8 Participants |
| Sham Control | Modified Rankin Scale Response: The Proportion of Subjects That Improved at Least One Point on the mRS From Baseline | Non-responder | 35 Participants |
Comparison: Combined SB623 Implant Vs Sham Surgery group at Month 6p-value: 0.195% CI: [0.15, 1.18]Mixed Models Analysis
Secondary
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.
Time frame: 6 Months
Population: Modified Intent-to-Treat (mITT) Population: Included all randomized subjects who completed the surgery treatment procedure. A total of 111 subjects received treatment with SB623; 55 subjects were randomized to receive 2.5 million SB623 cells and 56 subjects to receive 5 million SB623 cells.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| SB623 Implant (2.5M) | Neurological Quality of Life Response: T-scores of the Change From Baseline in the 2 Sub-domains (Upper Extremity Function and Lower Extremity Function) | Upper Extremity Function | 0.14 Change in score on a scale from baseline | Standard Error 2.018 |
| SB623 Implant (2.5M) | Neurological Quality of Life Response: T-scores of the Change From Baseline in the 2 Sub-domains (Upper Extremity Function and Lower Extremity Function) | Lower Extremity Function | 1.61 Change in score on a scale from baseline | Standard Error 1.343 |
| SB623 Implant (5.0M) | Neurological Quality of Life Response: T-scores of the Change From Baseline in the 2 Sub-domains (Upper Extremity Function and Lower Extremity Function) | Upper Extremity Function | -1.08 Change in score on a scale from baseline | Standard Error 2 |
| SB623 Implant (5.0M) | Neurological Quality of Life Response: T-scores of the Change From Baseline in the 2 Sub-domains (Upper Extremity Function and Lower Extremity Function) | Lower Extremity Function | 2.74 Change in score on a scale from baseline | Standard Error 1.331 |
| Sham Control | Neurological Quality of Life Response: T-scores of the Change From Baseline in the 2 Sub-domains (Upper Extremity Function and Lower Extremity Function) | Upper Extremity Function | -0.11 Change in score on a scale from baseline | Standard Error 1.946 |
| Sham Control | Neurological Quality of Life Response: T-scores of the Change From Baseline in the 2 Sub-domains (Upper Extremity Function and Lower Extremity Function) | Lower Extremity Function | 1.60 Change in score on a scale from baseline | Standard Error 1.301 |
Comparison: Statistical analysis: NeuroQOL score for the Upper Extremity Function (Represents Mean Change from Baseline in T-Scores at Month 6)p-value: 0.778895% CI: [-2.9, 2.17]Mixed Models Analysis
Comparison: Statistical Analysis: NeuroQOL score for Lower Extremity Function (Represents Mean Change from Baseline in T-Scores at Month 6)p-value: 0.534795% CI: [-1.26, 2.43]Mixed Models Analysis
Secondary
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
Time frame: 6 months
Population: Modified Intent-to-Treat (mITT) Population: Included all randomized subjects who completed the surgery treatment procedure. A total of 111 subjects received treatment with SB623; 55 subjects were randomized to receive 2.5 million SB623 cells and 56 subjects to receive 5 million SB623 cells.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SB623 Implant (2.5M) | The Proportion of Subjects That Improved at Least 1 Functional Level From Baseline on Gait Velocity | Non-respinder | 39 Participants |
| SB623 Implant (2.5M) | The Proportion of Subjects That Improved at Least 1 Functional Level From Baseline on Gait Velocity | Responder | 7 Participants |
| SB623 Implant (2.5M) | The Proportion of Subjects That Improved at Least 1 Functional Level From Baseline on Gait Velocity | Unknown | 9 Participants |
| SB623 Implant (5.0M) | The Proportion of Subjects That Improved at Least 1 Functional Level From Baseline on Gait Velocity | Non-respinder | 43 Participants |
| SB623 Implant (5.0M) | The Proportion of Subjects That Improved at Least 1 Functional Level From Baseline on Gait Velocity | Responder | 6 Participants |
| SB623 Implant (5.0M) | The Proportion of Subjects That Improved at Least 1 Functional Level From Baseline on Gait Velocity | Unknown | 7 Participants |
| Sham Control | The Proportion of Subjects That Improved at Least 1 Functional Level From Baseline on Gait Velocity | Responder | 5 Participants |
| Sham Control | The Proportion of Subjects That Improved at Least 1 Functional Level From Baseline on Gait Velocity | Unknown | 11 Participants |
| Sham Control | The Proportion of Subjects That Improved at Least 1 Functional Level From Baseline on Gait Velocity | Non-respinder | 36 Participants |
Secondary
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.
Time frame: 6 months
Population: Modified Intent-to-Treat (mITT) Population: Included all randomized subjects who completed the surgery treatment procedure. A total of 111 subjects received treatment with SB623; 55 subjects were randomized to receive 2.5 million SB623 cells and 56 subjects to receive 5 million SB623 cells.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SB623 Implant (2.5M) | The Proportion of Subjects That Improved at Least 6 Points From Baseline on the ARAT Total Score at the Affected Side | Non-responder | 47 Participants |
| SB623 Implant (2.5M) | The Proportion of Subjects That Improved at Least 6 Points From Baseline on the ARAT Total Score at the Affected Side | Responder | 6 Participants |
| SB623 Implant (2.5M) | The Proportion of Subjects That Improved at Least 6 Points From Baseline on the ARAT Total Score at the Affected Side | Unknown | 2 Participants |
| SB623 Implant (5.0M) | The Proportion of Subjects That Improved at Least 6 Points From Baseline on the ARAT Total Score at the Affected Side | Non-responder | 45 Participants |
| SB623 Implant (5.0M) | The Proportion of Subjects That Improved at Least 6 Points From Baseline on the ARAT Total Score at the Affected Side | Responder | 9 Participants |
| SB623 Implant (5.0M) | The Proportion of Subjects That Improved at Least 6 Points From Baseline on the ARAT Total Score at the Affected Side | Unknown | 2 Participants |
| Sham Control | The Proportion of Subjects That Improved at Least 6 Points From Baseline on the ARAT Total Score at the Affected Side | Responder | 9 Participants |
| Sham Control | The Proportion of Subjects That Improved at Least 6 Points From Baseline on the ARAT Total Score at the Affected Side | Unknown | 6 Participants |
| Sham Control | The Proportion of Subjects That Improved at Least 6 Points From Baseline on the ARAT Total Score at the Affected Side | Non-responder | 37 Participants |
Other Pre-specified
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.
Time frame: 6 Months
Population: Modified Intent-to-Treat (mITT) Population: Included all randomized subjects who completed the surgery treatment procedure. A total of 111 subjects received treatment with SB623; 55 subjects were randomized to receive 2.5 million SB623 cells and 56 subjects to receive 5 million SB623 cells.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| SB623 Implant (2.5M) | Additional Analysis (MMRM), Fugl-Meyer Motor Scale (FMMS) | 5.3 Change in score on a scale from baseline | Standard Error 1.64 |
| SB623 Implant (5.0M) | Additional Analysis (MMRM), Fugl-Meyer Motor Scale (FMMS) | 4.5 Change in score on a scale from baseline | Standard Error 1.62 |
| Sham Control | Additional Analysis (MMRM), Fugl-Meyer Motor Scale (FMMS) | 3.6 Change in score on a scale from baseline | Standard Error 1.59 |
Comparison: Change from Baseline at Month 6~Between-group Effect size is calculated as the LS mean difference divided by the model estimate of the pooled SD, obtained from the square root of the diagonal element, associated with the analysis visit summarized, from the covariance matrix.p-value: 0.295995% CI: [-1.1, 3.6]Mixed Models Analysis
Other Pre-specified
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
Time frame: Month 6
Population: Per Protocol (PP) Population: The PP population included all subjects in the mITT population who did not have important protocol deviations.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SB623 Implant (2.5M) | Proportion of Subjects Whose FMMS Motor Total Score Improve by ≥10 Points at Month 6 From Baseline (Per Protocol Population) | Unknown | 1 Participants |
| SB623 Implant (2.5M) | Proportion of Subjects Whose FMMS Motor Total Score Improve by ≥10 Points at Month 6 From Baseline (Per Protocol Population) | Non-responder | 34 Participants |
| SB623 Implant (2.5M) | Proportion of Subjects Whose FMMS Motor Total Score Improve by ≥10 Points at Month 6 From Baseline (Per Protocol Population) | Responder | 6 Participants |
| SB623 Implant (5.0M) | Proportion of Subjects Whose FMMS Motor Total Score Improve by ≥10 Points at Month 6 From Baseline (Per Protocol Population) | Non-responder | 35 Participants |
| SB623 Implant (5.0M) | Proportion of Subjects Whose FMMS Motor Total Score Improve by ≥10 Points at Month 6 From Baseline (Per Protocol Population) | Responder | 9 Participants |
| SB623 Implant (5.0M) | Proportion of Subjects Whose FMMS Motor Total Score Improve by ≥10 Points at Month 6 From Baseline (Per Protocol Population) | Unknown | 2 Participants |
| Sham Control | Proportion of Subjects Whose FMMS Motor Total Score Improve by ≥10 Points at Month 6 From Baseline (Per Protocol Population) | Responder | 7 Participants |
| Sham Control | Proportion of Subjects Whose FMMS Motor Total Score Improve by ≥10 Points at Month 6 From Baseline (Per Protocol Population) | Unknown | 4 Participants |
| Sham Control | Proportion of Subjects Whose FMMS Motor Total Score Improve by ≥10 Points at Month 6 From Baseline (Per Protocol Population) | Non-responder | 35 Participants |
Comparison: Combined SB623 Implant Vs Sham Surgery group at Month 6p-value: 0.685495% CI: [0.31, 5.92]Mixed Models Analysis