Investigation of Neural Stem Cells in Ischemic Stroke

A Randomized, Placebo-Controlled Study of the Efficacy and Safety of Intracerebral Stem Cells (CTX0E03) in Subjects With Disability Following an Ischemic Stroke

A study of stereotactic, intracerebral injection of CTX0E03 neural stem cells into patients with moderate to moderately severe disability as a result of an ischemic stroke.

This is a randomized, placebo-controlled, multi-center study. Patients with persistent disability 6-24 months following an ischemic stroke will be enrolled following confirmation of eligibility. Patients will be randomized 2:1 to undergo a stereotactic surgery and receive a single administration of CTX0E03 Drug Product by intracerebral implantation or undergo sham surgery only (placebo). Patients will be followed for 12 months after surgery with follow-up assessments occurring at various time points over the 12 months. All eligible patients will be assigned a standardized Physical Therapy (PT) program. Patients will complete their daily PT exercises at home for 12 weeks after their surgery.

Inclusion Criteria:

• Ischemic stroke that includes the supratentorial region as confirmed by CT or MRI, occurring within 6 to 24 months of the time that surgical intervention will be performed (Qualifying Stroke Event)
• Modified Rankin Score of 3 or 4 due to the Qualifying Stroke Event
• Some residual upper limb movement
• Sufficient cognitive and language abilities to comprehend verbal commands and to carry out the study assessments
• No medical conditions that would preclude neurosurgery with appropriate preparation and management.
• Ability to attend study visits and complete all study assessments including ability to provide informed consent

Exclusion Criteria:

• Modified Rankin Score of >1 prior to the Qualifying Stroke Event
• Stroke due to hemorrhage or stroke known or suspected of being caused by, or related to, connective tissue disorder, congenital disorder of the cerebral vessels or a disorder of thrombosis; patients with atrial fibrillation as a suspected cause of stroke are NOT excluded
• Neurosurgical pathway obstructed by vascular malformation or cavity
• History of neurological or other disease resulting in significant functional impairment (e.g. Parkinson's disease, motor neuron disease, moderate dementia, arthritis, contractures or fixed anatomical abnormality)
• Inability to stop or transition off valproic acid or other demethylating agents or Histone deacetylases (HDAC) inhibitors for 1 week before and 4 weeks after surgery
• Use of selective serotonin reuptake inhibitors (SSRI), unless the subject is on a stable dose that has been started at least 2-months before screening (V1)
• Use of antispasticity medications (excluding oral antispasticity medications if they have been taken regularly for at least one month prior to surgery)The use of Botox® or similar is allowed if the last dose was ≥3 months prior to screening; however, its use will be prohibited until following the 12 month visit
• Inability to discontinue anticoagulation therapy for a required interval
• History of malignant disease within the last 5 years, or any history of primary or secondary brain malignant disease
• Patients who have previously participated in a cell-based therapy study at any time or in any other study involving an investigational product or rehabilitation study within the last 30 days
• Patients with clinically significant lab values, including positive Class I human leukocyte antigen (HLA) antibodies specific for CTX0E03
• Planned initiation of any new PT regimen within 6-months of surgery