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

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)

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.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Biological: SB623 cells; Procedure: Sham Control

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).

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Hokkaido, Japan
    • Hokkaido University Hospital
  • Okayama, Japan
    • Okayama University Hospital
  • Osaka, Japan
    • Osaka University Hospital
  • Tokyo, Japan
    • University of Tokyo Hospital
  • Yokohama, Japan
    • Yokohama City University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital (Surgical/Assessment)
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 236-0004
      • Yokohama City University Hospital (Surgical/Assessment)
  • Okayama
    • Okayama-shi, Okayama, Japan, 700-8655
      • Okayama University Hospital (Assessment/Surgical)
  • Osaka
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital (Assessment/Surgical)
  • Tokyo
    • Bunkyo, Tokyo, Japan, 113-8655
      • University of Tokyo Hospital (Assessment/Surgical)
• Ukraine
  • Kiev, Ukraine, 03680
    • Clinical Hospital Feofaniia
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center (Surgical/Assessment)
    • Los Angeles, California, United States
      • Ronald Reagan UCLA Medical Denter
    • Oceanside, California, United States, 92056
      • The Research Center of Southern California, LLC (Assessment)
    • Orange, California, United States, 92868
      • University of California, Irvine (Assessment/Surgical)
    • Placentia, California, United States, 92870
      • Westview Clinical Research (Assessment)
    • Santa Monica, California, United States, 90404
      • Providence Saint John's Health Center
    • Santa Monica, California, United States
      • John Wayne Cancer Institute at Providence St. Johns Health Center
    • Stanford, California, United States, 94305
      • Stanford Health Care (Surgical/Assessment)
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Craig Hospital
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Ki Health Partners, LLC dba New England Institute for Clinical Research (Assessment)
  • Florida
    • Miami, Florida, United States, 33136
      • SouthCoast Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital (Surgical)
    • Atlanta, Georgia, United States, 30312
      • Midtown Neurology, PC (Assessment)
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Rehabilitation Institute of Chicago
    • Chicago, Illinois, United States
      • Shirley Ryan Ability Lab
  • New York
    • New York, New York, United States
      • New York University Langone Medical Center
    • New York, New York, United States, 10016
      • NYU Langone Medical Center (Surgical/Assessment)
    • White Plains, New York, United States, 10605
      • Burke Rehab Center (Assessment)
  • Ohio
    • Columbus, Ohio, United States, 43214
      • Ohio Health Research
  • Pennsylvania
    • Elkins Park, Pennsylvania, United States, 19027
      • Moss Rehab (Assessment)
    • Pittsburgh, Pennsylvania, United States
      • University of Pittsburgh School of Medicine
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center (Surgical/Assessment)
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (Surgical)
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University
  • Washington
    • Richland, Washington, United States, 99352
      • Mid-Columbia Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SB623 Cells; SB623 Cells: 2.5, 5 or 10 million cells	Biological: SB623 cells; SB623 cells will be implanted in the peri-infarct area using stereotactic surgery.
Sham Comparator: Sham Surgery; Control Sham Surgery	Procedure: Sham Control; Sham Surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: SanBio, Inc.
• Investigators: Principal Investigator: Daniel C Lu, MD, PhD, University of California, Los Angeles, Department of Neurosurgery

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2016
• Primary Completion (Actual): January 31, 2019
• Study Completion (Actual): March 5, 2019

Study Registration Dates

• First Submitted: April 6, 2015
• First Submitted That Met QC Criteria: April 9, 2015
• First Posted (Estimate): April 15, 2015

Study Record Updates

• Last Update Posted (Actual): December 27, 2021
• Last Update Submitted That Met QC Criteria: November 30, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Wounds and Injuries; Brain Injuries, Traumatic
• Other Study ID Numbers: TBI-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No