Clinical trial NCT03629275: Investigation of Neural Stem Cells in Ischemic Stroke
Official title: A Randomized, Placebo-Controlled Study of the Efficacy and Safety of Intracerebral Stem Cells (CTX0E03) in Subjects With Disability Following an Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ischemic Stroke
Chronic Stroke
Hemiparesis
Arm Paralysis
Keywords: Efficacy
Neural Stem cells
Intracerebral
Cerebral Infarction
Cerebrovascular disorders
Brain diseases
Stereotactic surgery
Lead sponsor: ReNeuron Limited
Sponsor class: INDUSTRY
First posted: 2018-08-14
Enrollment: 15
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of subjects in which Modified Rankin Scale (mRS) improves by ≥1 point at Month 6 from Baseline
timeFrame: 6 months
Secondary outcomes:
measure: Change from baseline in a subject's ability to execute activities of daily living using the Barthel Index (BI).
timeFrame: 6 months
measure: Change from baseline in a subject's basic mobility and balance using the Timed Up and Go Test (TUG).
timeFrame: 6 months
measure: Change from baseline in the function of subject's paretic limb using the Chedoke Arm and Hand Activity Inventory (CAHAI).
timeFrame: 6 months
measure: Change from baseline in a subject's executive processing speed, language skills and memory using the Symbol Digit Modalities Test.
timeFrame: 6 months
measure: Change from baseline in a subject's executive processing speed, language skills and memory using Controlled Oral Word Association tasks.
timeFrame: 6 months
measure: Change from baseline in a subject's executive processing speed, language skills and memory using the Multilingual Naming Test.
timeFrame: 6 months
measure: Change from baseline in a subject's executive processing speed, language skills and memory using the Montreal Cognitive Assessment.
timeFrame: 6 months
measure: Change from baseline in a subject's neurological deficits using the National Institute of Health Stroke Scale (NIHSS).
timeFrame: 6 months
measure: Change from baseline in restoring a subject's motor function using the Fugl-Meyer Assessment of Motor Recovery after Stroke (FMA).
timeFrame: 6 months
measure: Change from baseline in subject's global rating of change regarding their limitations of activity, symptoms, and overall quality of life.
timeFrame: 6 months
measure: Change from baseline in a subject's perception to stroke recovery using the Stroke Impact Scale (SIS).
timeFrame: 6 months
measure: Change from baseline in a subject's health-related quality of life using the EQ-5D-5L.
timeFrame: 6 months
measure: Safety: To assess the number and severity of adverse events and medical device incidents that occur over the study period.
timeFrame: 12 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas
state: Arkansas
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Los Angeles
country: United States
facility: University of Southern California Neurorestoration Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Coral Gables
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Chicago
country: United States
facility: Shirley Ryan Ability Lab
state: Illinois
city: Hyattsville
country: United States
facility: MedStar Health Research Institute
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Edison
country: United States
facility: JFK Neuroscience Institute
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Chattanooga
country: United States
facility: Chattanooga Center for Neurologic Research
state: Tennessee
city: Houston
country: United States
facility: University of Texas Health Science Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center
state: Texas
Study officials:
affiliation: ReNeuron Ltd.
name: Richard Beckman, MD
role: STUDY_DIRECTOR
References:
citation: Olmsted ZT, Petersen EA, Pilitsis JG, Rahimi SY, Chen PR, Savitz SI, Laskowitz DT, Kolls BJ, Staudt MD. Toward Generalizable Trajectory Planning for Human Intracerebral Trials and Therapy. Stereotact Funct Neurosurg. 2022;100(4):214-223. doi: 10.1159/000521916. Epub 2022 Feb 7.