A Study of Modified Stem Cells in Traumatic Brain Injury (TBI)

Phase 2

Completed

Conditions: Traumatic Brain Injury

Interventions: Procedure: Sham Control
Biological: SB623 cells

Registration Number: NCT02416492

Lead Sponsor: SanBio, Inc.

Brief Summary: The primary purpose of the clinical study is to evaluate the clinical efficacy of intracranial administration of SB623 cells on patients with chronic motor deficit from Traumatic Brain Injury. A secondary purpose of the study is 1) to evaluate the effect of intracranial administration of SB623 cells on disability parameters and 2) to evaluate the safety and tolerability of intracranial administration of SB623 cells. Patients with stable, chronic motor deficits secondary to focal traumatic brain injury must be 12 months post TBI.

Detailed Description: This study was a multicenter, randomized (3:1) double-blind, active and sham-surgery controlled study to evaluate the safety, tolerability, and efficacy of stereotactic intracranial injection of SB623 cells in patients with fixed motor deficits from TBI. The study was conducted at approximately 22 sites across the United States, Ukraine, and Japan.

Two groups, Group 1 and Group 2, received investigational product SB623 and sham surgery, respectively, in a 3:1 randomization scheme. Group 1 was further randomized in a 1:1:1 ratio to receive either 2.5 million, 5 million, or 10 million SB623 cells. Randomization was performed via an interactive web response system (IWRS).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 63

Inclusion Criteria

Documented history of TBI, with correlated MRI or CT
At least 12 months post-TBI
Focal cerebral injury able to be identified on MRI (+/- concomitant diffuse axonal injury)
Neurological motor deficit substantially due to focal cerebral injury observed on MRI
GOS-E score of 3-6 (i.e. moderate or severe disability)
Require Motricity Index 10-81 (UE Scale) and/or 10-78 (LE Scale)
Able and willing to undergo computed tomography (CT) and magnetic resonance imaging (MRI)
Subjects must be willing to participate in study related exercises to the extent possible
Able to undergo all planned neurological assessments

Exclusion Criteria

History or presence of any other major neurological disease
Any seizures in the prior 3 months
The presence of contracture at any joints that would interfere with interpretation of any of the neurological assessments (e.g. contracture preventing the detection of any increase in the range of motion or ability to perform a task)
Other neurologic, neuromuscular or orthopedic disease that limits motor function
Clincially significant finding on MRI of brain not related to TBI
Known presence of any malignancy except squamous or basal cell carcinoma of the skin
History of CNS malignancy
Positive findings on tests for occult malignancy, unless a non-malignant etiology is confirmed
Uncontrolled systemic illness, including, but not limited to: hypertension (systolic >150 mm Hg or diastolic >95 mm Hg); diabetes; renal, hepatic, or cardiac failure
Uncontrolled major psychiatric illness, including depression symptoms (CESD-R Scale of ≥16)
Unexplained abnormal preoperative test values (blood tests, electrocardiogram [ECG], chest X-ray); x-ray evidence of infection; uncontrolled atrial fibrillation or uncontrolled congestive heart failure
Presence of craniectomy (without bone flap replacement) or other contraindication to stereotactic surgery
Participation in any other investigational trial within 4 weeks of initial screening or within 7 weeks of study entry
Botulinum toxin injection, phenol injection, intrathecal baclofen, or any other interventional treatments for spasticity (except bracing and splinting) 16 weeks priot to the Baseline visit.
Ongoing use of other non-traditional drugs
Substance use disorder (per DSM-V criteria, including drug or alcohol)
Contraindications to head CT or MRI
Pregnant or lactating
Female patients of childbearing potential unwilling to use an adequate birth control method during the 12 months of the study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham Surgery	Sham Control	Control Sham Surgery
SB623 Cells	SB623 cells	SB623 Cells: 2.5, 5 or 10 million cells

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Fugl-Meyer Motor Scale (FMMS) Score at Week 24 Among All Patients	24 weeks	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).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Gait Velocity (10 Meter Walk Time in Seconds) at Week 24 Among Lower Extremity Deficit Patients	24 weeks	Gait Velocity was measured on a standard 10 meter walk.
Change From Baseline in Disability Rating Scale Score at Week 24 Among All Patients	24 weeks	DRS is an observer rated, 30-point ordinal scale that evaluates eight areas of functioning in four categories: 1. Consciousness (eye opening, verbal response, motor response) 2. Cognitive ability (feeding, toileting, grooming) 3. Dependence on others 4. Employability Each area of functioning was rated on a scale of 0 to either 3 or 5. The maximum score is 29 (extreme vegetative state) and the minimum score is 0 (person without disability).
Change From Baseline in ARAT Total Score at Week 24 Among Upper Extremity Deficit Patients	24 weeks	The ARAT total score is the sum of the scores from 19 tests spread across four subscales: grasp, grip, pinch, and gross movement. Each test is scored on an ordinal 4-point scale with 0= non movement, 1 = the movement task is partially performed, 2 = the movement task is completed but takes abnormally long, and 3 = the movement is performed normally. Summation of a 0-3 score in each item yields a total score between 0 and 57.
Change From Baseline in NeuroQOL T-scores at Week 24 of NeuroQOL Domains	24 weeks	Two NeuroQoL short form assessments were used (upper extremity function and lower extremity function); each has 8 items with 5 possible scores (e.g. 1= not at all, 2=a little bit, 3= somewhat, 4=quite a bit, 5=very much) or frequency ("never"to "always"); Raw scores are converted to T-scores based on a consistent metric (i.e., the T distribution) and data from the US general population. The theoretical range in scale for Upper extremity T-score and Lower extremity T-score are 12.8 to 53.8 and 16.5 to 58.6 respectively. When interpreting these T-scores, higher scores correspond to higher levels of functioning whereas lower scores correspond to lower levels of functioning.
Global Rating of Perceived Change: The Percentage of Subjects Scoring Either 6 or 7 on the Global Rating of Perceived Change by Both Subject and Physician	24 weeks	The proportions of SB623 treated subjects (pooling all SB623 doses) scoring either 7 (much better) or 6 (a little better, meaningful) on the Global Rating of Perceived Change (from Baseline) - Subject at Week 24 and on the Global Rating of Perceived Change (from Baseline) - Clinician at Week 24 was compared to the corresponding proportions of sham surgery control subjects using logistic regression models with adjustment for the baseline Fugl-Meyer Motor Scale score and the GOS-E score at screening as continuous covariates. 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

Trial Locations

Locations (36): Ronald Reagan UCLA Medical Denter
🇺🇸
Los Angeles, California, United States
Providence Saint John's Health Center
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Santa Monica, California, United States
University of Pittsburgh Medical Center (Surgical/Assessment)
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Pittsburgh, Pennsylvania, United States
Rehabilitation Institute of Chicago
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Chicago, Illinois, United States
Shirley Ryan Ability Lab
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Chicago, Illinois, United States
University of Pittsburgh School of Medicine
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Pittsburgh, Pennsylvania, United States
UCLA Medical Center (Surgical/Assessment)
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Los Angeles, California, United States
University of California, Irvine (Assessment/Surgical)
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Orange, California, United States
Westview Clinical Research (Assessment)
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Placentia, California, United States
Craig Hospital
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Englewood, Colorado, United States
SouthCoast Research Center
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Miami, Florida, United States
Ki Health Partners, LLC dba New England Institute for Clinical Research (Assessment)
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Stamford, Connecticut, United States
NYU Langone Medical Center (Surgical/Assessment)
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New York, New York, United States
New York University Langone Medical Center
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New York, New York, United States
Moss Rehab (Assessment)
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Elkins Park, Pennsylvania, United States
Ohio Health Research
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Columbus, Ohio, United States
Hokkaido University Hospital (Surgical/Assessment)
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Sapporo, Hokkaido, Japan
Okayama University Hospital (Assessment/Surgical)
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Okayama-shi, Okayama, Japan
Hokkaido University Hospital
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Hokkaido, Japan
Osaka University Hospital (Assessment/Surgical)
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Suita, Osaka, Japan
Okayama University Hospital
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Okayama, Japan
University of Tokyo Hospital
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Tokyo, Japan
Osaka University Hospital
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Osaka, Japan
Clinical Hospital Feofaniia
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Kiev, Ukraine
The Research Center of Southern California, LLC (Assessment)
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Oceanside, California, United States
Emory University Hospital (Surgical)
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Atlanta, Georgia, United States
Mid-Columbia Research
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Richland, Washington, United States
Stanford Health Care (Surgical/Assessment)
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Stanford, California, United States
John Wayne Cancer Institute at Providence St. Johns Health Center
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Santa Monica, California, United States
Midtown Neurology, PC (Assessment)
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Atlanta, Georgia, United States
Burke Rehab Center (Assessment)
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White Plains, New York, United States
University of Tokyo Hospital (Assessment/Surgical)
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Bunkyo, Tokyo, Japan
Yokohama City University Hospital (Surgical/Assessment)
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Yokohama, Kanagawa, Japan
Yokohama City University Hospital
🇯🇵
Yokohama, Japan
Medical University of South Carolina (Surgical)
🇺🇸
Charleston, South Carolina, United States
Virginia Commonwealth University
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Richmond, Virginia, United States