Ischemic StrokePhase 2PISCES IIINCT03629275
Investigation of Neural Stem Cells in Ischemic Stroke
A Phase 2 study testing CTX0E03 Drug Product and delivery device in people with Ischemic Stroke and Chronic Stroke, run by ReNeuron Limited at 23 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Ischemic Stroke, Chronic Stroke, Hemiparesis
- What is being tested?
- CTX0E03 Drug Product and delivery device
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 23 sitesUnited States
- Study dates
- 31 Aug 2018to 2 Mar 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 12Show fewer
- 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
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
United States23 sites
Albany Medical College
Albany, New York, 12208
Emory
Atlanta, Georgia, 30322
Augusta University
Augusta, Georgia, 30912
Chattanooga Center for Neurologic Research
Chattanooga, Tennessee, 37403
Shirley Ryan Ability Lab
Chicago, Illinois, 60611
University of Miami
Coral Gables, Florida, 33146
Henry Ford Health System
Detroit, Michigan, 48202
Duke University School of Medicine
Durham, North Carolina, 27705
JFK Neuroscience Institute
Edison, New Jersey, 08820
University of Texas Health Science Center
Houston, Texas, 77030
MedStar Health Research Institute
Hyattsville, Maryland, 20782
University of California, Irvine
Irvine, California, 92697
University of Arkansas
Little Rock, Arkansas, 72205
University of California, Los Angeles
Los Angeles, California, 90095
University of Southern California Neurorestoration Center
Los Angeles, California, 90095
Stanford University
Palo Alto, California, 94304
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Oregon Health and Science University
Portland, Oregon, 97239
University of Texas Health Science Center
San Antonio, Texas, 78229-3900
University of California, San Diego
San Diego, California, 92093-0706
Washington University School of Medicine
St Louis, Missouri, 63130
University of South Florida
Tampa, Florida, 33606
About this study
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
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.
Read the 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.
- Conditions
- Ischemic Stroke, Chronic Stroke, Hemiparesis, Arm Paralysis
- Being tested
- CTX0E03 Drug Product and delivery device, Placebo
- Keywords
- Efficacy, Neural Stem cells, Intracerebral, Cerebral Infarction, Cerebrovascular disorders, Brain diseases, Stereotactic surgery
- Medical subject headings
- Ischemic Stroke, Paresis, Cerebral Infarction, Cerebrovascular Disorders, Brain Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CTX0E03 Drug Product and delivery deviceCombination product
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| CTX0E03 Drug Product and delivery device | Experimental | 20 million neural stem cells Receives: Combination Product: CTX0E03 Drug Product and delivery device |
| Placebo | Sham comparator | Sham Surgery Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 6 months
Safety: To assess the number and severity of adverse events and medical device incidents that occur over the study period.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2018
- Study start31 Aug 2018
- Primary completion9 Sep 2020
- Study completion2 Mar 2021
Why it stopped: Strategic decision to progress stroke disability programme through regional partnerships
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- ReNeuron Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Richard Beckman, MD, Study director, ReNeuron Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03629275
- Sponsor's protocol ID
- RN01-CP-0003
- Acronym
- PISCES III
- Status last verified
- Aug 2021
- First submitted
- 23 Jul 2018
- Last updated
- 13 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Publications
Laskowitz DT, Muir KW, Savitz SI, Wechsler LR, Pilitsis JG, Rahimi SY, Beckman RL, Holmes V, Chen PR, Juel L, Koltai D, Kolls BJ. Methodological considerations in PISCES 3: a randomized, placebo-controlled study of intracerebral stem cells in subjects with disability following an ischemic stroke. Front Stroke. 2023 Jul 4;2:1182537. doi: 10.3389/fstro.2023.1182537. eCollection 2023.
PubMed 41541089Kolls BJ, Muir KW, Savitz SI, Wechsler LR, Pilitsis JG, Rahimi S, Beckman RL, Holmes V, Chen PR, Albers DS, Laskowitz DT. Experience with a hybrid recruitment approach of patient-facing web portal screening and subsequent phone and medical record review for a neurosurgical intervention trial for chronic ischemic stroke disability (PISCES III). Trials. 2024 Feb 28;25(1):150. doi: 10.1186/s13063-024-07988-z.
PubMed 38419030Olmsted 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.
PubMed 35130557
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03629275
- Acronym / sponsor ID
- PISCES III / RN01-CP-0003
- Conditions
- Ischemic Stroke, Chronic Stroke, Hemiparesis, Arm Paralysis
- Keywords
- Efficacy, Neural Stem cells, Intracerebral, Cerebral Infarction, Cerebrovascular disorders, Brain diseases, Stereotactic surgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Strategic decision to progress stroke disability programme through regional partnerships
- Enrolment
- 15 participants (actual)
- Lead sponsor
- ReNeuron LimitedIndustry (pharma, biotech, devices)
- Study start
- 31 Aug 2018 (actual)
- Primary completion
- 9 Sep 2020 (actual)
- Study completion
- 2 Mar 2021 (actual)
- First posted
- 14 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CTX0E03 Drug Product and delivery device | Experimental | Combination Product: CTX0E03 Drug Product and delivery device20 million neural stem cells |
| Placebo | Sham comparator | Drug: PlaceboSham Surgery |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CTX0E03 Drug Product and delivery deviceIncludes 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. | Combination product | CTX0E03 Drug Product and delivery device |
| PlaceboSham 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. | Drug | Placebo |
Primary outcome
Proportion of subjects in which Modified Rankin Scale (mRS) improves by ≥1 point at Month 6 from Baseline
Time frame: 6 months
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.
13 secondary outcomes
Change from baseline in a subject's ability to execute activities of daily living using the Barthel Index (BI).
Time frame: 6 months
Change from baseline in a subject's basic mobility and balance using the Timed Up and Go Test (TUG).
Time frame: 6 months
Change from baseline in the function of subject's paretic limb using the Chedoke Arm and Hand Activity Inventory (CAHAI).
Time frame: 6 months
Change from baseline in a subject's executive processing speed, language skills and memory using the Symbol Digit Modalities Test.
Time frame: 6 months
Change from baseline in a subject's executive processing speed, language skills and memory using Controlled Oral Word Association tasks.
Time frame: 6 months
Change from baseline in a subject's executive processing speed, language skills and memory using the Multilingual Naming Test.
Time frame: 6 months
Change from baseline in a subject's executive processing speed, language skills and memory using the Montreal Cognitive Assessment.
Time frame: 6 months
Change from baseline in a subject's neurological deficits using the National Institute of Health Stroke Scale (NIHSS).
Time frame: 6 months
Change from baseline in restoring a subject's motor function using the Fugl-Meyer Assessment of Motor Recovery after Stroke (FMA).
Time frame: 6 months
Change from baseline in subject's global rating of change regarding their limitations of activity, symptoms, and overall quality of life.
Time frame: 6 months
Change from baseline in a subject's perception to stroke recovery using the Stroke Impact Scale (SIS).
Time frame: 6 months
Change from baseline in a subject's health-related quality of life using the EQ-5D-5L.
Time frame: 6 months
Safety: To assess the number and severity of adverse events and medical device incidents that occur over the study period.
Time frame: 12 months
Results and safety
The study was stopped early (reason given: Strategic decision to progress stroke disability programme through regional partnerships). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2021.
- Derived from this study: PubMed 41541089Laskowitz DT, Muir KW, Savitz SI, Wechsler LR, Pilitsis JG, Rahimi SY, Beckman RL, Holmes V, Chen PR, Juel L, Koltai D, Kolls BJ. Methodological considerations in PISCES 3: a randomized, placebo-controlled study of intracerebral stem cells in subjects with disability following an ischemic stroke. Front Stroke. 2023 Jul 4;2:1182537. doi: 10.3389/fstro.2023.1182537. eCollection 2023.
- Derived from this study: PubMed 38419030Kolls BJ, Muir KW, Savitz SI, Wechsler LR, Pilitsis JG, Rahimi S, Beckman RL, Holmes V, Chen PR, Albers DS, Laskowitz DT. Experience with a hybrid recruitment approach of patient-facing web portal screening and subsequent phone and medical record review for a neurosurgical intervention trial for chronic ischemic stroke disability (PISCES III). Trials. 2024 Feb 28;25(1):150. doi: 10.1186/s13063-024-07988-z.
- Derived from this study: PubMed 35130557Olmsted 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.
Related trials for Ischemic Stroke
Not yet recruiting
Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke
Acute Ischemic Stroke
RecruitingObservational study
ELATE Study: Evaluating Large-vessel Acute Thrombectomy in Extended Time Window
Acute Ichemic Stroke
Not yet recruiting
Selective Intra-Arterial Hypothermia After Endovascular Treatment for Acute Basilar Artery Occlusion
Acute Ischemic Stroke, Basilar Artery Occlusion
Active, not recruiting
Improving Visual Field Deficits With Noninvasive Brain Stimulation
Visual Field Defect, Peripheral, Stroke
Recruiting
Biomarkers of Paired VNS
Stroke, Ischemic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Beckman, MD study director
ReNeuron Ltd.
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CTX0E03 Drug Product and delivery device in people with Ischemic Stroke and Chronic Stroke, run by ReNeuron Limited at 23 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Strategic decision to progress stroke disability programme through regional partnerships). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of subjects in which Modified Rankin Scale (mRS) improves by ≥1 point at Month 6 from Baseline (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03629275, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2021.