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

Primary Purpose

Ischemic Stroke, Chronic Stroke, Hemiparesis

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CTX0E03 Drug Product and delivery device
Placebo
Sponsored by
ReNeuron Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke focused on measuring Efficacy, Neural Stem cells, Intracerebral, Cerebral Infarction, Cerebrovascular disorders, Brain diseases, Stereotactic surgery

Eligibility Criteria

35 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Arkansas
  • University of California, Irvine
  • University of California, Los Angeles
  • University of Southern California Neurorestoration Center
  • Stanford University
  • University of California, San Diego
  • University of Miami
  • University of South Florida
  • Emory
  • Augusta University
  • Shirley Ryan Ability Lab
  • MedStar Health Research Institute
  • Henry Ford Health System
  • Washington University School of Medicine
  • JFK Neuroscience Institute
  • Albany Medical College
  • Duke University School of Medicine
  • Oregon Health and Science University
  • University of Pennsylvania
  • University of Pittsburgh
  • Chattanooga Center for Neurologic Research
  • University of Texas Health Science Center
  • University of Texas Health Science Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

CTX0E03 Drug Product and delivery device

Placebo

Arm Description

20 million neural stem cells

Sham Surgery

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Safety: To assess the number and severity of adverse events and medical device incidents that occur over the study period.

Full Information

First Posted
July 23, 2018
Last Updated
August 12, 2021
Sponsor
ReNeuron Limited
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1. Study Identification

Unique Protocol Identification Number
NCT03629275
Brief Title
Investigation of Neural Stem Cells in Ischemic Stroke
Acronym
PISCES III
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

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
Strategic decision to progress stroke disability programme through regional partnerships
Study Start Date
August 31, 2018 (Actual)
Primary Completion Date
September 9, 2020 (Actual)
Study Completion Date
March 2, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ReNeuron Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke, Chronic Stroke, Hemiparesis, Arm Paralysis
Keywords
Efficacy, Neural Stem cells, Intracerebral, Cerebral Infarction, Cerebrovascular disorders, Brain diseases, Stereotactic surgery

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CTX0E03 Drug Product and delivery device
Arm Type
Experimental
Arm Description
20 million neural stem cells
Arm Title
Placebo
Arm Type
Sham Comparator
Arm Description
Sham Surgery
Intervention Type
Combination Product
Intervention Name(s)
CTX0E03 Drug Product and delivery device
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Proportion of subjects in which Modified Rankin Scale (mRS) improves by ≥1 point at Month 6 from Baseline
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Change from baseline in a subject's ability to execute activities of daily living using the Barthel Index (BI).
Description
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.
Time Frame
6 months
Title
Change from baseline in a subject's basic mobility and balance using the Timed Up and Go Test (TUG).
Description
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.
Time Frame
6 months
Title
Change from baseline in the function of subject's paretic limb using the Chedoke Arm and Hand Activity Inventory (CAHAI).
Description
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.
Time Frame
6 months
Title
Change from baseline in a subject's executive processing speed, language skills and memory using the Symbol Digit Modalities Test.
Description
Validated test assessing different aspects of cognitive function.
Time Frame
6 months
Title
Change from baseline in a subject's executive processing speed, language skills and memory using Controlled Oral Word Association tasks.
Description
Validated test assessing different aspects of cognitive function.
Time Frame
6 months
Title
Change from baseline in a subject's executive processing speed, language skills and memory using the Multilingual Naming Test.
Description
Validated test assessing different aspects of cognitive function.
Time Frame
6 months
Title
Change from baseline in a subject's executive processing speed, language skills and memory using the Montreal Cognitive Assessment.
Description
Validated test assessing different aspects of cognitive function.
Time Frame
6 months
Title
Change from baseline in a subject's neurological deficits using the National Institute of Health Stroke Scale (NIHSS).
Description
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.
Time Frame
6 months
Title
Change from baseline in restoring a subject's motor function using the Fugl-Meyer Assessment of Motor Recovery after Stroke (FMA).
Description
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.
Time Frame
6 months
Title
Change from baseline in subject's global rating of change regarding their limitations of activity, symptoms, and overall quality of life.
Description
Self-administered 2 factor questionnaire assessing change in limitations of activity, symptoms, and overall quality of life.
Time Frame
6 months
Title
Change from baseline in a subject's perception to stroke recovery using the Stroke Impact Scale (SIS).
Description
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.
Time Frame
6 months
Title
Change from baseline in a subject's health-related quality of life using the EQ-5D-5L.
Description
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.
Time Frame
6 months
Title
Safety: To assess the number and severity of adverse events and medical device incidents that occur over the study period.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Beckman, MD
Organizational Affiliation
ReNeuron Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
University of Arkansas
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
University of California, Irvine
City
Irvine
State/Province
California
ZIP/Postal Code
92697
Country
United States
Facility Name
University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Southern California Neurorestoration Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of California, San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92093-0706
Country
United States
Facility Name
University of Miami
City
Coral Gables
State/Province
Florida
ZIP/Postal Code
33146
Country
United States
Facility Name
University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
Emory
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Shirley Ryan Ability Lab
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
MedStar Health Research Institute
City
Hyattsville
State/Province
Maryland
ZIP/Postal Code
20782
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Facility Name
JFK Neuroscience Institute
City
Edison
State/Province
New Jersey
ZIP/Postal Code
08820
Country
United States
Facility Name
Albany Medical College
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Duke University School of Medicine
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Chattanooga Center for Neurologic Research
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37403
Country
United States
Facility Name
University of Texas Health Science Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Texas Health Science Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229-3900
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35130557
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.
Results Reference
derived

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Investigation of Neural Stem Cells in Ischemic Stroke

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