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

NCT ID: NCT02416492

Last Updated: 2021-12-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-06

Study Completion Date

2019-03-05

Brief Summary

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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

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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).

Conditions

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Traumatic Brain Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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SB623 Cells

SB623 Cells: 2.5, 5 or 10 million cells

Group Type EXPERIMENTAL

SB623 cells

Intervention Type BIOLOGICAL

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

Sham Surgery

Control Sham Surgery

Group Type SHAM_COMPARATOR

Sham Control

Intervention Type PROCEDURE

Sham Surgery

Interventions

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SB623 cells

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

Intervention Type BIOLOGICAL

Sham Control

Sham Surgery

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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SanBio, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel C Lu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles, Department of Neurosurgery

Locations

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UCLA Medical Center (Surgical/Assessment)

Los Angeles, California, United States

Site Status

Ronald Reagan UCLA Medical Denter

Los Angeles, California, United States

Site Status

The Research Center of Southern California, LLC (Assessment)

Oceanside, California, United States

Site Status

University of California, Irvine (Assessment/Surgical)

Orange, California, United States

Site Status

Westview Clinical Research (Assessment)

Placentia, California, United States

Site Status

Providence Saint John's Health Center

Santa Monica, California, United States

Site Status

John Wayne Cancer Institute at Providence St. Johns Health Center

Santa Monica, California, United States

Site Status

Stanford Health Care (Surgical/Assessment)

Stanford, California, United States

Site Status

Craig Hospital

Englewood, Colorado, United States

Site Status

Ki Health Partners, LLC dba New England Institute for Clinical Research (Assessment)

Stamford, Connecticut, United States

Site Status

SouthCoast Research Center

Miami, Florida, United States

Site Status

Midtown Neurology, PC (Assessment)

Atlanta, Georgia, United States

Site Status

Emory University Hospital (Surgical)

Atlanta, Georgia, United States

Site Status

Rehabilitation Institute of Chicago

Chicago, Illinois, United States

Site Status

Shirley Ryan Ability Lab

Chicago, Illinois, United States

Site Status

NYU Langone Medical Center (Surgical/Assessment)

New York, New York, United States

Site Status

New York University Langone Medical Center

New York, New York, United States

Site Status

Burke Rehab Center (Assessment)

White Plains, New York, United States

Site Status

Ohio Health Research

Columbus, Ohio, United States

Site Status

Moss Rehab (Assessment)

Elkins Park, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center (Surgical/Assessment)

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, United States

Site Status

Medical University of South Carolina (Surgical)

Charleston, South Carolina, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Mid-Columbia Research

Richland, Washington, United States

Site Status

Hokkaido University Hospital (Surgical/Assessment)

Sapporo, Hokkaido, Japan

Site Status

Yokohama City University Hospital (Surgical/Assessment)

Yokohama, Kanagawa, Japan

Site Status

Okayama University Hospital (Assessment/Surgical)

Okayama, Okayama-ken, Japan

Site Status

Osaka University Hospital (Assessment/Surgical)

Suita, Osaka, Japan

Site Status

University of Tokyo Hospital (Assessment/Surgical)

Bunkyo, Tokyo, Japan

Site Status

Hokkaido University Hospital

Hokkaido, , Japan

Site Status

Okayama University Hospital

Okayama, , Japan

Site Status

Osaka University Hospital

Osaka, , Japan

Site Status

University of Tokyo Hospital

Tokyo, , Japan

Site Status

Yokohama City University Hospital

Yokohama, , Japan

Site Status

Clinical Hospital Feofaniia

Kiev, , Ukraine

Site Status

Countries

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United States Japan Ukraine

References

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Okonkwo DO, McAllister P, Achrol AS, Karasawa Y, Kawabori M, Cramer SC, Lai A, Kesari S, Frishberg BM, Groysman LI, Kim AS, Schwartz NE, Chen JW, Imai H, Yasuhara T, Chida D, Nejadnik B, Bates D, Stonehouse AH, Richardson RM, Steinberg GK, Poggio EC, Weintraub AH. Mesenchymal Stromal Cell Implants for Chronic Motor Deficits After Traumatic Brain Injury: Post Hoc Analysis of a Randomized Trial. Neurology. 2024 Oct 8;103(7):e209797. doi: 10.1212/WNL.0000000000209797. Epub 2024 Sep 4.

Reference Type DERIVED
PMID: 39231380 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34402352 (View on PubMed)

Kawabori M, Weintraub AH, Imai H, Zinkevych I, McAllister P, Steinberg GK, Frishberg BM, Yasuhara T, Chen JW, Cramer SC, Achrol AS, Schwartz NE, Suenaga J, Lu DC, Semeniv I, Nakamura H, Kondziolka D, Chida D, Kaneko T, Karasawa Y, Paadre S, Nejadnik B, Bates D, Stonehouse AH, Richardson RM, Okonkwo DO. Cell Therapy for Chronic TBI: Interim Analysis of the Randomized Controlled STEMTRA Trial. Neurology. 2021 Feb 22;96(8):e1202-e1214. doi: 10.1212/WNL.0000000000011450.

Reference Type DERIVED
PMID: 33397772 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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TBI-01

Identifier Type: -

Identifier Source: org_study_id