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

Primary Purpose

Traumatic Brain Injury

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SB623 cells
Sham Control
Sponsored by
SanBio, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Traumatic Brain Injury

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UCLA Medical Center (Surgical/Assessment)
  • Ronald Reagan UCLA Medical Denter
  • The Research Center of Southern California, LLC (Assessment)
  • University of California, Irvine (Assessment/Surgical)
  • Westview Clinical Research (Assessment)
  • Providence Saint John's Health Center
  • John Wayne Cancer Institute at Providence St. Johns Health Center
  • Stanford Health Care (Surgical/Assessment)
  • Craig Hospital
  • Ki Health Partners, LLC dba New England Institute for Clinical Research (Assessment)
  • SouthCoast Research Center
  • Midtown Neurology, PC (Assessment)
  • Emory University Hospital (Surgical)
  • Rehabilitation Institute of Chicago
  • Shirley Ryan Ability Lab
  • NYU Langone Medical Center (Surgical/Assessment)
  • New York University Langone Medical Center
  • Burke Rehab Center (Assessment)
  • Ohio Health Research
  • Moss Rehab (Assessment)
  • University of Pittsburgh Medical Center (Surgical/Assessment)
  • University of Pittsburgh School of Medicine
  • Medical University of South Carolina (Surgical)
  • Virginia Commonwealth University
  • Mid-Columbia Research
  • Hokkaido University Hospital (Surgical/Assessment)
  • Yokohama City University Hospital (Surgical/Assessment)
  • Okayama University Hospital (Assessment/Surgical)
  • Osaka University Hospital (Assessment/Surgical)
  • University of Tokyo Hospital (Assessment/Surgical)
  • Hokkaido University Hospital
  • Okayama University Hospital
  • Osaka University Hospital
  • University of Tokyo Hospital
  • Yokohama City University Hospital
  • Clinical Hospital Feofaniia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

SB623 Cells

Sham Surgery

Arm Description

SB623 Cells: 2.5, 5 or 10 million cells

Control Sham Surgery

Outcomes

Primary Outcome Measures

Change From Baseline in Fugl-Meyer Motor Scale (FMMS) Score at Week 24 Among All Patients
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

Change From Baseline in Disability Rating Scale Score at Week 24 Among All Patients
DRS is an observer rated, 30-point ordinal scale that evaluates eight areas of functioning in four categories: Consciousness (eye opening, verbal response, motor response) Cognitive ability (feeding, toileting, grooming) Dependence on others 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
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 Gait Velocity (10 Meter Walk Time in Seconds) at Week 24 Among Lower Extremity Deficit Patients
Gait Velocity was measured on a standard 10 meter walk.
Change From Baseline in NeuroQOL T-scores at Week 24 of NeuroQOL Domains
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
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

Full Information

First Posted
April 6, 2015
Last Updated
November 30, 2021
Sponsor
SanBio, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02416492
Brief Title
A Study of Modified Stem Cells in Traumatic Brain Injury (TBI)
Acronym
STEMTRA
Official Title
A Double-Blind, Controlled Phase 2 Study of the Safety and Efficacy of Modified Stem Cells (SB623) in Patients With Chronic Motor Deficit From Traumatic Brain Injury (TBI)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
July 6, 2016 (Actual)
Primary Completion Date
January 31, 2019 (Actual)
Study Completion Date
March 5, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SanBio, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SB623 Cells
Arm Type
Experimental
Arm Description
SB623 Cells: 2.5, 5 or 10 million cells
Arm Title
Sham Surgery
Arm Type
Sham Comparator
Arm Description
Control Sham Surgery
Intervention Type
Biological
Intervention Name(s)
SB623 cells
Intervention Description
SB623 cells will be implanted in the peri-infarct area using stereotactic surgery.
Intervention Type
Procedure
Intervention Name(s)
Sham Control
Intervention Description
Sham Surgery
Primary Outcome Measure Information:
Title
Change From Baseline in Fugl-Meyer Motor Scale (FMMS) Score at Week 24 Among All Patients
Description
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).
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in Disability Rating Scale Score at Week 24 Among All Patients
Description
DRS is an observer rated, 30-point ordinal scale that evaluates eight areas of functioning in four categories: Consciousness (eye opening, verbal response, motor response) Cognitive ability (feeding, toileting, grooming) Dependence on others 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).
Time Frame
24 weeks
Title
Change From Baseline in ARAT Total Score at Week 24 Among Upper Extremity Deficit Patients
Description
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.
Time Frame
24 weeks
Title
Change From Baseline in Gait Velocity (10 Meter Walk Time in Seconds) at Week 24 Among Lower Extremity Deficit Patients
Description
Gait Velocity was measured on a standard 10 meter walk.
Time Frame
24 weeks
Title
Change From Baseline in NeuroQOL T-scores at Week 24 of NeuroQOL Domains
Description
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.
Time Frame
24 weeks
Title
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
Description
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
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel C Lu, MD, PhD
Organizational Affiliation
University of California, Los Angeles, Department of Neurosurgery
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCLA Medical Center (Surgical/Assessment)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Ronald Reagan UCLA Medical Denter
City
Los Angeles
State/Province
California
Country
United States
Facility Name
The Research Center of Southern California, LLC (Assessment)
City
Oceanside
State/Province
California
ZIP/Postal Code
92056
Country
United States
Facility Name
University of California, Irvine (Assessment/Surgical)
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Westview Clinical Research (Assessment)
City
Placentia
State/Province
California
ZIP/Postal Code
92870
Country
United States
Facility Name
Providence Saint John's Health Center
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
John Wayne Cancer Institute at Providence St. Johns Health Center
City
Santa Monica
State/Province
California
Country
United States
Facility Name
Stanford Health Care (Surgical/Assessment)
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Craig Hospital
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
Ki Health Partners, LLC dba New England Institute for Clinical Research (Assessment)
City
Stamford
State/Province
Connecticut
ZIP/Postal Code
06905
Country
United States
Facility Name
SouthCoast Research Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Midtown Neurology, PC (Assessment)
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30312
Country
United States
Facility Name
Emory University Hospital (Surgical)
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Rehabilitation Institute of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Shirley Ryan Ability Lab
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
NYU Langone Medical Center (Surgical/Assessment)
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
New York University Langone Medical Center
City
New York
State/Province
New York
Country
United States
Facility Name
Burke Rehab Center (Assessment)
City
White Plains
State/Province
New York
ZIP/Postal Code
10605
Country
United States
Facility Name
Ohio Health Research
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43214
Country
United States
Facility Name
Moss Rehab (Assessment)
City
Elkins Park
State/Province
Pennsylvania
ZIP/Postal Code
19027
Country
United States
Facility Name
University of Pittsburgh Medical Center (Surgical/Assessment)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Pittsburgh School of Medicine
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
Facility Name
Medical University of South Carolina (Surgical)
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23219
Country
United States
Facility Name
Mid-Columbia Research
City
Richland
State/Province
Washington
ZIP/Postal Code
99352
Country
United States
Facility Name
Hokkaido University Hospital (Surgical/Assessment)
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
Yokohama City University Hospital (Surgical/Assessment)
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
236-0004
Country
Japan
Facility Name
Okayama University Hospital (Assessment/Surgical)
City
Okayama-shi
State/Province
Okayama
ZIP/Postal Code
700-8655
Country
Japan
Facility Name
Osaka University Hospital (Assessment/Surgical)
City
Suita
State/Province
Osaka
ZIP/Postal Code
565-0871
Country
Japan
Facility Name
University of Tokyo Hospital (Assessment/Surgical)
City
Bunkyo
State/Province
Tokyo
ZIP/Postal Code
113-8655
Country
Japan
Facility Name
Hokkaido University Hospital
City
Hokkaido
Country
Japan
Facility Name
Okayama University Hospital
City
Okayama
Country
Japan
Facility Name
Osaka University Hospital
City
Osaka
Country
Japan
Facility Name
University of Tokyo Hospital
City
Tokyo
Country
Japan
Facility Name
Yokohama City University Hospital
City
Yokohama
Country
Japan
Facility Name
Clinical Hospital Feofaniia
City
Kiev
ZIP/Postal Code
03680
Country
Ukraine

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34402352
Citation
McCrea MA, Cramer SC, Okonkwo DO, Mattke S, Paadre S, Bates D, Nejadnik B, Giacino JT. Determining minimally clinically important differences for outcome measures in patients with chronic motor deficits secondary to traumatic brain injury. Expert Rev Neurother. 2021 Sep;21(9):1051-1058. doi: 10.1080/14737175.2021.1968299. Epub 2021 Aug 26.
Results Reference
derived

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

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