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

Traumatic Brain Injury Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02416492
• Other study ID #: TBI-01
• Status: Completed
• Phase: Phase 2
• Start date: July 6, 2016
• Est. completion date: March 5, 2019

Study information

• Verified date: November 2021
• Source: SanBio, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: March 5, 2019
• Est. primary completion date: January 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Biological:
• SB623 cells
SB623 cells will be implanted in the peri-infarct area using stereotactic surgery.

Procedure:
• Sham Control
Sham Surgery

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
SanBio, Inc.

Countries where clinical trial is conducted

United States,  Japan,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	24 weeks
Secondary	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).	24 weeks
Secondary	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.	24 weeks
Secondary	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.	24 weeks
Secondary	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.	24 weeks
Secondary	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	24 weeks