Clinical trial NCT02416492: A Study of Modified Stem Cells in Traumatic Brain Injury (TBI)
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Traumatic Brain Injury
Lead sponsor: SanBio, Inc.
Sponsor class: INDUSTRY
First posted: 2015-04-15
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Change From Baseline in Fugl-Meyer Motor Scale (FMMS) Score at Week 24 Among All Patients
timeFrame: 24 weeks
Secondary outcomes:
measure: Change From Baseline in Disability Rating Scale Score at Week 24 Among All Patients
timeFrame: 24 weeks
measure: Change From Baseline in ARAT Total Score at Week 24 Among Upper Extremity Deficit Patients
timeFrame: 24 weeks
measure: Change From Baseline in Gait Velocity (10 Meter Walk Time in Seconds) at Week 24 Among Lower Extremity Deficit Patients
timeFrame: 24 weeks
measure: Change From Baseline in NeuroQOL T-scores at Week 24 of NeuroQOL Domains
timeFrame: 24 weeks
measure: 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
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center (Surgical/Assessment)
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Denter
state: California
city: Oceanside
country: United States
facility: The Research Center of Southern California, LLC (Assessment)
state: California
city: Orange
country: United States
facility: University of California, Irvine (Assessment/Surgical)
state: California
city: Placentia
country: United States
facility: Westview Clinical Research (Assessment)
state: California
city: Santa Monica
country: United States
facility: Providence Saint John's Health Center
state: California
city: Santa Monica
country: United States
facility: John Wayne Cancer Institute at Providence St. Johns Health Center
state: California
city: Stanford
country: United States
facility: Stanford Health Care (Surgical/Assessment)
state: California
city: Englewood
country: United States
facility: Craig Hospital
state: Colorado
city: Stamford
country: United States
facility: Ki Health Partners, LLC dba New England Institute for Clinical Research (Assessment)
state: Connecticut
city: Miami
country: United States
facility: SouthCoast Research Center
state: Florida
city: Atlanta
country: United States
facility: Midtown Neurology, PC (Assessment)
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital (Surgical)
state: Georgia
city: Chicago
country: United States
facility: Rehabilitation Institute of Chicago
state: Illinois
city: Chicago
country: United States
facility: Shirley Ryan Ability Lab
state: Illinois
city: New York
country: United States
facility: NYU Langone Medical Center (Surgical/Assessment)
state: New York
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: White Plains
country: United States
facility: Burke Rehab Center (Assessment)
state: New York
city: Columbus
country: United States
facility: Ohio Health Research
state: Ohio
city: Elkins Park
country: United States
facility: Moss Rehab (Assessment)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (Surgical/Assessment)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh School of Medicine
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (Surgical)
state: South Carolina
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Richland
country: United States
facility: Mid-Columbia Research
state: Washington
city: Sapporo
country: Japan
facility: Hokkaido University Hospital (Surgical/Assessment)
state: Hokkaido
city: Yokohama
country: Japan
facility: Yokohama City University Hospital (Surgical/Assessment)
state: Kanagawa
city: Okayama-shi
country: Japan
facility: Okayama University Hospital (Assessment/Surgical)
state: Okayama
city: Suita
country: Japan
facility: Osaka University Hospital (Assessment/Surgical)
state: Osaka
city: Bunkyo
country: Japan
facility: University of Tokyo Hospital (Assessment/Surgical)
state: Tokyo
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: University of Tokyo Hospital
city: Yokohama
country: Japan
facility: Yokohama City University Hospital
city: Kiev
country: Ukraine
facility: Clinical Hospital Feofaniia
Study officials:
affiliation: University of California, Los Angeles, Department of Neurosurgery
name: Daniel C Lu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.