Study of Modified Stem Cells (SB623) in Patients With Chr... | NCT02448641

Name	Class
Sumitomo Pharma America, Inc.	INDUSTRY

Label	Type	Description	Intervention Names
SB623 Implant (2.5M)	Experimental	2.5 million SB623 cells	Biological: SB623 Implant (2.5M)
SB623 Implant (5.0M)	Experimental	5 million SB623 cells	Biological: SB623 Implant (5.0M)
Sham Control	Sham Comparator	Sham surgery	Procedure: Sham surgery

Name	Type	Description	Arm Group Labels	Other Names
SB623 Implant (2.5M)	Biological	2.5 million SB623 cells	SB623 Implant (2.5M)

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

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.

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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age 18-75 years, inclusive
Documented history of completed ischemic stroke in subcortical region of MCA or lenticulostriate artery with or without cortical involvement, with correlated findings by MRI
Between 6 and 90 months (7.5 years) post-stroke, and having a chronic motor neurological deficit
Neurological motor deficit substantially due to incident stroke
Modified Rankin Score of 2-4
Require Motricity Index 30-75 (UE Scale) or 27-74 (LE Scale)
Able to undergo all planned neurological assessments
Able and willing to undergo magneti resonance imaging (MRI) with contrast and computed tomography (CT)
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
Subjects must have had physical therapy prior to entry (and be willing to continue to the extent possible)
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
Ability of patient or legal authorized representative to understand and sign an Informed Consent

Exclusion Criteria:

History or presence of any other major neurological disease other than stroke
Cerebral infarct size >150 cm3 measured by MRI
Primary intracerebral hemorrhage
Myocardial infarction within prior 6 mos.
Malignancy unless in remission >5 yrs.
Clinically significant finding on MRI of brain not related to stroke
Any seizures in the 3 months prior to Screening
More than 5 degrees of contracture at shoulder, elbow, wrist, fingers, hip, knee and ankle
Other neurologic, neuromuscular or orthopedic disease that limits motor function
Uncontrolled systemic illness, including, but not limited to: hypertension; diabetes; renal, hepatic, or cardiac failure
Positive findings on tests for occult malignancy, unless a non-malignant etiology is confirmed
Uncontrolled major psychiatric illness, including depression symptoms (CESD R Scale of ≥16 is exclusionary)
Total bilirubin >1.9 mg/dL at Screening
Serum creatinine >1.5 mg/dL at Screening
Hemoglobin <10.0 g/dL at Screening
Absolute neutrophil count <2000 /mm3 at Screening
Absolute lymphocytes <800 /mm3 at Screening
Platelet count <100,000 /mm3 at Screening
Liver disease supported by AST (SGOT) or ALT (SGPT) ≥2.5 x upper limit of normal at Screening
Serum calcium >11.5 mg/dL at Screening
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
Presence of craniectomy or other contraindication to stereotactic surgery
Participation in any other investigational trial within 4 weeks of initial screening and within 7 weeks of Baseline visit
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
Substance use disorder (per DSM-V criteria, including drug or alcohol)
Contraindications to head MRI (with constrast) or CT
Pregnant or lactating
Female patients of childbearing potential unwilling to use an adequate birth control method during the 12 months of the study
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
Any prior SB623 cell implantation and/or any prior stem cell treatment for stroke or other reason regardless of mode of administration

Name	Affiliation	Role
Gary Steinberg, MD, PhD	Stanford Hospital and Clinics, School of Medicine	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham (Surgical/Assessment)		Birmingham	Alabama	35233	United States

ID	Title	Description
FG000	SB623 Implant (2.5M)	2.5 million SB623 cells SB623 Implant (2.5M): 2.5 million SB623 cells
FG001	SB623 Implant (5.0M)	5 million SB623 cells SB623 Implant (5.0M): 5 million SB623 cells

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 5, 2017	Dec 20, 2019

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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

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.

Posted

Count of Participants

Participants

6 months

ID	Title	Description
OG000	SB623 Implant (2.5M)	2.5 million SB623 cells SB623 Implant (2.5M): 2.5 million SB623 cells
OG001	SB623 Implant (5.0M)	5 million SB623 cells SB623 Implant (5.0M): 5 million SB623 cells
OG002	Sham Control	Sham surgery Sham surgery

Units	Counts
Participants	OG00055 OG00156 OG00252

Title

Denominators

Categories

Responder

Title	Measurements
	OG0007 OG0019 OG0027

Non-responder

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002	Combined SB623 Implant Vs Sham Surgery group at Month 6	Mixed Models Analysis	A GLMM with FMMS responder as outcome, treatment, visit, treatment-visit interaction, pooled site, Baseline FMMS and Baseline mRS scores as covariates	0.6743	GLMM: Generalized Linear Mixed Model	Odds Ratio (OR)	1.33			2-Sided	95	0.35	5.09					Superiority

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.

Posted

Count of Participants

Participants

6 months

ID	Title	Description
OG000	SB623 Implant (2.5M)	2.5 million SB623 cells
OG001	SB623 Implant (5.0M)	5 million SB623 cells
OG002	Sham Control	Sham surgery Group

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.

Posted

Count of Participants

Participants

6 months

ID	Title	Description
OG000	SB623 Implant (2.5M)	2.5 million SB623 cells
OG001	SB623 Implant (5.0M)

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

Posted

Count of Participants

Participants

6 months

ID	Title	Description
OG000	SB623 Implant (2.5M)	2.5 million SB623 cells SB623 Implant (2.5M): 2.5 million SB623 cells
OG001	SB623 Implant (5.0M)	5 million SB623 cells SB623 Implant (5.0M): 5 million SB623 cells
OG002	Sham Control	Sham surgery Sham surgery

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.

Posted

Least Squares Mean

Standard Error

Change in score on a scale from baseline

6 Months

ID	Title	Description
OG000	SB623 Implant (2.5 M)	2.5 million SB623 cells SB623 Implant (2.5M): 2.5 million SB623 cells
OG001	SB623 Implant (5.0M)	5.0 million SB623 cells SB623 Implant (5.0M): 5.0 million SB623 cells

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)

Posted

Count of Participants

Participants

6 Months (LOCF)

ID	Title	Description
OG000	SB623 Implant (2.5M)	2.5 million SB623 cells SB623 Implant (2.5M): 2.5 million SB623 cells
OG001	SB623 Implant (5.0M)	5 million SB623 cells SB623 Implant (5.0M): 5 million SB623 cells

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.

Posted

Least Squares Mean

Standard Error

Change in score on a scale from baseline

6 Months

ID	Title	Description
OG000	SB623 Implant (2.5 M)	2.5 million SB623 cells SB623 Implant (2.5M): 2.5 million SB623 cells
OG001	SB623 Implant (5.0M)	5.0 million SB623 cells SB623 Implant (5.0M): 5.0 million SB623 cells
OG002	Sham Surgery	Sham surgery: Control Group

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

Per Protocol (PP) Population: The PP population included all subjects in the mITT population who did not have important protocol deviations.

Posted

Count of Participants

Participants

Month 6

ID	Title	Description
OG000	SB623 Implant (2.5M)	2.5 million SB623 cells SB623 Implant (2.5M): 2.5 million SB623 cells
OG001	SB623 Implant (5.0M)	5 million SB623 cells SB623 Implant (5.0M): 5 million SB623 cells
OG002	Sham Control	Sham surgery Sham surgery

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Haemorrhagic anaemia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Leukocytosis	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0011 events1 affected56 at risk EG0020 events0 affected52 at risk
Atrial fibrillation	Cardiac disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0011 events1 affected56 at risk EG0020 events0 affected52 at risk
Pericardial effusion	Cardiac disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Ventricular tachycardia	Cardiac disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Bradycardia	Cardiac disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0010 events0 affected56 at risk EG0021 events1 affected52 at risk
Vertigo	Ear and labyrinth disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Pancreatitis	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0010 events0 affected56 at risk EG0021 events1 affected52 at risk
Pyrexia	General disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0012 events2 affected56 at risk EG0020 events0 affected52 at risk
Asthenia	General disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0011 events1 affected56 at risk EG0020 events0 affected52 at risk
Chest pain	General disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG0003 events2 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Sepsis	Infections and infestations	Systematic Assessment	EG0002 events1 affected55 at risk EG0010 events0 affected56 at risk EG0021 events1 affected52 at risk
Pancreas infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected55 at risk EG0011 events1 affected56 at risk EG0020 events0 affected52 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected55 at risk EG0011 events1 affected56 at risk EG0020 events0 affected52 at risk
Wound infection	Infections and infestations	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Bronchopneumonia	Infections and infestations	Systematic Assessment	EG0000 events0 affected55 at risk EG0010 events0 affected56 at risk EG0021 events1 affected52 at risk
Cellulitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected55 at risk EG0010 events0 affected56 at risk EG0021 events1 affected52 at risk
Influenza	Infections and infestations	Systematic Assessment	EG0000 events0 affected55 at risk EG0010 events0 affected56 at risk EG0021 events1 affected52 at risk
Intervertebral discitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected55 at risk EG0010 events0 affected56 at risk EG0021 events1 affected52 at risk
Staphylococcal osteomyelitis	Infections and infestations	Systematic Assessment	EG0000 events0 affected55 at risk EG0010 events0 affected56 at risk EG0021 events1 affected52 at risk
Subdural haematoma	Injury, poisoning and procedural complications	Systematic Assessment	EG0003 events3 affected55 at risk EG0011 events1 affected56 at risk EG0020 events0 affected52 at risk
Subdural haemorrhage	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected55 at risk EG0012 events2 affected56 at risk EG0020 events0 affected52 at risk
Contusion	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Crush injury	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected55 at risk EG0011 events1 affected56 at risk EG0020 events0 affected52 at risk
Hip fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected55 at risk EG0011 events1 affected56 at risk EG0020 events0 affected52 at risk
Humerus fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Incision site complication	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Ligament sprain	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Pneumocephalus	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected55 at risk EG0011 events1 affected56 at risk EG0020 events0 affected52 at risk
Upper limb fracture	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Wound dehiscence	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Anti factor X antibody positive	Investigations	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Hyponatraemia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0011 events1 affected56 at risk EG0020 events0 affected52 at risk
Muscle haemorrhage	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0011 events1 affected56 at risk EG0020 events0 affected52 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 events0 affected55 at risk EG0011 events1 affected56 at risk EG0020 events0 affected52 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Systematic Assessment	EG0000 events0 affected55 at risk EG0010 events0 affected56 at risk EG0021 events1 affected52 at risk
Seizure	Nervous system disorders	Systematic Assessment	EG0004 events4 affected55 at risk EG0015 events4 affected56 at risk EG0024 events3 affected52 at risk
Basal ganglia haemorrhage	Nervous system disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Generalised tonic-clonic seizure	Nervous system disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Seizure like phenomena	Nervous system disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Syncope	Nervous system disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0011 events1 affected56 at risk EG0020 events0 affected52 at risk
Encephalopathy	Nervous system disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0010 events0 affected56 at risk EG0021 events1 affected52 at risk
Transient ischaemic attack	Nervous system disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0010 events0 affected56 at risk EG0021 events1 affected52 at risk
Suicidal ideation	Psychiatric disorders	Systematic Assessment	EG0002 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Renal failure	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0011 events1 affected56 at risk EG0020 events0 affected52 at risk
Urinary retention	Renal and urinary disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk
Acute kidney injury	Renal and urinary disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0010 events0 affected56 at risk EG0021 events1 affected52 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0010 events0 affected56 at risk EG0021 events1 affected52 at risk
Hypotension	Vascular disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0010 events0 affected56 at risk EG0020 events0 affected52 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Eye swelling	Eye disorders	Systematic Assessment	EG0003 events3 affected55 at risk EG0011 events1 affected56 at risk EG0021 events1 affected52 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG00013 events13 affected55 at risk EG00112 events12 affected56 at risk EG0023 events3 affected52 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG00010 events10 affected55 at risk EG0016 events6 affected56 at risk EG0021 events1 affected52 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0005 events5 affected55 at risk EG0012 events2 affected56 at risk EG0025 events4 affected52 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0003 events3 affected55 at risk EG0011 events1 affected56 at risk EG0021 events1 affected52 at risk
Fatigue	General disorders	Systematic Assessment	EG0003 events3 affected55 at risk EG0013 events3 affected56 at risk EG0024 events4 affected52 at risk
Pyrexia	General disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0013 events3 affected56 at risk EG0021 events1 affected52 at risk
Pain	General disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0013 events3 affected56 at risk EG0020 events0 affected52 at risk
Urinary tract infection	Infections and infestations	Systematic Assessment	EG0003 events2 affected55 at risk EG0015 events5 affected56 at risk EG0020 events0 affected52 at risk
Upper respiratory tract infection	Infections and infestations	Systematic Assessment	EG0000 events0 affected55 at risk EG0015 events4 affected56 at risk EG0022 events2 affected52 at risk
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected55 at risk EG0012 events2 affected56 at risk EG0023 events3 affected52 at risk
Procedural headache	Injury, poisoning and procedural complications	Systematic Assessment	EG0009 events8 affected55 at risk EG0019 events9 affected56 at risk EG00213 events13 affected52 at risk
Procedural pain	Injury, poisoning and procedural complications	Systematic Assessment	EG00011 events11 affected55 at risk EG0015 events5 affected56 at risk EG0026 events6 affected52 at risk
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0008 events5 affected55 at risk EG0015 events5 affected56 at risk EG00212 events4 affected52 at risk
Incision site pain	Injury, poisoning and procedural complications	Systematic Assessment	EG0005 events5 affected55 at risk EG0015 events5 affected56 at risk EG00210 events10 affected52 at risk
Contusion	Injury, poisoning and procedural complications	Systematic Assessment	EG0004 events2 affected55 at risk EG0013 events3 affected56 at risk EG0021 events1 affected52 at risk
Skin abrasion	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected55 at risk EG0013 events3 affected56 at risk EG0023 events2 affected52 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0014 events4 affected56 at risk EG0021 events1 affected52 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0014 events4 affected56 at risk EG0025 events5 affected52 at risk
Headache	Nervous system disorders	Systematic Assessment	EG00042 events35 affected55 at risk EG00148 events41 affected56 at risk EG00235 events32 affected52 at risk
Paraesthesia	Nervous system disorders	Systematic Assessment	EG0001 events1 affected55 at risk EG0014 events3 affected56 at risk EG0022 events2 affected52 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0000 events0 affected55 at risk EG0015 events3 affected56 at risk EG0021 events1 affected52 at risk
Depression	Psychiatric disorders	Systematic Assessment	EG0007 events6 affected55 at risk EG0013 events3 affected56 at risk EG0020 events0 affected52 at risk
Swelling face	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0003 events2 affected55 at risk EG0012 events2 affected56 at risk EG0025 events5 affected52 at risk

ID	Term
D020521	Stroke
D002561	Cerebrovascular Disorders
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D014652	Vascular Diseases
D002318	Cardiovascular Diseases

ID	Title	Description
BG000	SB623 Implant (2.5M)	2.5 million SB623 cells
BG001	SB623 Implant (5.0M)	5 million SB623 cells
BG002	Sham Control	Control Group: Sham surgery
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	SB623 Implant (2.5M)	2.5 million SB623 cells SB623 Implant (2.5M): 2.5 million SB623 cells	0	55	15	55	52	55
EG001	SB623 Implant (5.0M)	5 million SB623 cells SB623 Implant (5.0M): 5 million SB623 cells	1	56	15	56	53	56
EG002	Sham Control	Control Group: Sham surgery Group	0	52	10	52	51	52