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

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.

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).

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