Investigation of Neural Stem Cells in Ischemic Stroke (PISCES III)

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.

Study Overview

• Status: Terminated
• Conditions: Ischemic Stroke; Hemiparesis; Chronic Stroke; Arm Paralysis
• Intervention / Treatment: Combination product: CTX0E03 Drug Product and delivery device; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
    • Los Angeles, California, United States, 90095
      • University of Southern California Neurorestoration Center
    • Palo Alto, California, United States, 94304
      • Stanford University
    • San Diego, California, United States, 92093-0706
      • University of California, San Diego
  • Florida
    • Coral Gables, Florida, United States, 33146
      • University of Miami
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Shirley Ryan Ability Lab
  • Maryland
    • Hyattsville, Maryland, United States, 20782
      • MedStar Health Research Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University School of Medicine
  • New Jersey
    • Edison, New Jersey, United States, 08820
      • JFK Neuroscience Institute
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University School of Medicine
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Chattanooga Center for Neurologic Research
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CTX0E03 Drug Product and delivery device; 20 million neural stem cells	Combination product: CTX0E03 Drug Product and delivery device; Includes stereotactic surgery and a burr hole drilled through the skull to allow for a one time intracerebral injection of 20 million CTX0E03 Drug Product stem cells into an area of the brain adjacent to the area affected by the stroke.
Sham Comparator: Placebo; Sham Surgery	Drug: Placebo; Sham surgical comparator includes stereotactic surgery and a partial thickness burr hole drilled into the skull. No injection of any kind is made into the brain, and no other intervention is given.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects in which Modified Rankin Scale (mRS) improves by ≥1 point at Month 6 from Baseline	The mRS is an ordinal scale from 0-6, where 0 represents no disability, and each grade above 0 represents a subject's increased level of disability and dependence upon others to perform daily activities.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in a subject's ability to execute activities of daily living using the Barthel Index (BI).	The BI is an ordinal scale used to measure a patient's ability to perform activities of daily living. Sum scores from 10 items are calculated with total possible scores ranging from 0-100, with lower scores indicating increased disability.	6 months
Change from baseline in a subject's basic mobility and balance using the Timed Up and Go Test (TUG).	TUG is a timed activity assessing mobility and balance in which subjects are asked to stand up from a chair, walk a distance of 3 meters, turn around, walk back to chair and seat themselves. Scores consist of time taken to complete the activity, in seconds.	6 months
Change from baseline in the function of subject's paretic limb using the Chedoke Arm and Hand Activity Inventory (CAHAI).	The CAHAI is validated to assess paretic limb function and consists of 13 functional tasks, each scored on a 7-point scale, with total test scores obtained by summing each task score. Total scores can range from 13-91 with higher scores indicating greater ability.	6 months
Change from baseline in a subject's executive processing speed, language skills and memory using the Symbol Digit Modalities Test.	Validated test assessing different aspects of cognitive function.	6 months
Change from baseline in a subject's executive processing speed, language skills and memory using Controlled Oral Word Association tasks.	Validated test assessing different aspects of cognitive function.	6 months
Change from baseline in a subject's executive processing speed, language skills and memory using the Multilingual Naming Test.	Validated test assessing different aspects of cognitive function.	6 months
Change from baseline in a subject's executive processing speed, language skills and memory using the Montreal Cognitive Assessment.	Validated test assessing different aspects of cognitive function.	6 months
Change from baseline in a subject's neurological deficits using the National Institute of Health Stroke Scale (NIHSS).	The NIHSS is comprised of 15 items used to assess severity of impairment due to stroke with each item scored on a 3 or 4 point ordinal scale in which 0 represents no impairment. Total sum score range from 0-42: higher score reflects greater severity.	6 months
Change from baseline in restoring a subject's motor function using the Fugl-Meyer Assessment of Motor Recovery after Stroke (FMA).	The FMA is used to assess motor function in post-stroke, hemiplegic patients. The FMA is comprised of 5 sections, and respective items within each section are scored using a 3-point ordinal scale with 0 representing inability to perform task. Total possible score is 226.	6 months
Change from baseline in subject's global rating of change regarding their limitations of activity, symptoms, and overall quality of life.	Self-administered 2 factor questionnaire assessing change in limitations of activity, symptoms, and overall quality of life.	6 months
Change from baseline in a subject's perception to stroke recovery using the Stroke Impact Scale (SIS).	The SIS is a stroke-specific, comprehensive measure of health status. The SIS is comprised of 59 items with each item rated on a 5 point Likert scale in terms difficulty. A score of 1 represents an inability to complete an item, where a score of 5 represents no difficulty.	6 months
Change from baseline in a subject's health-related quality of life using the EQ-5D-5L.	Subjects rate each of 5 dimensions with a numerical rating (1-5) where 1 represents no difficulty to 5 representing an inability, and where a lower total score represents better quality of life.	6 months
Safety: To assess the number and severity of adverse events and medical device incidents that occur over the study period.		12 months

Collaborators and Investigators

• Sponsor: ReNeuron Limited
• Investigators: Study Director: Richard Beckman, MD, ReNeuron Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2018
• Primary Completion (Actual): September 9, 2020
• Study Completion (Actual): March 2, 2021

Study Registration Dates

• First Submitted: July 23, 2018
• First Submitted That Met QC Criteria: August 10, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): August 13, 2021
• Last Update Submitted That Met QC Criteria: August 12, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Efficacy; Stereotactic surgery; Brain diseases; Cerebrovascular disorders; Cerebral Infarction; Intracerebral; Neural Stem cells
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Paralysis; Paresis
• Other Study ID Numbers: RN01-CP-0003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes