Ischaemic StrokePhase 2PISCES-IINCT02117635
Pilot Investigation of Stem Cells in Stroke Phase II Efficacy
A Phase 2 study testing CTX DP in people with Ischaemic Stroke and Cerebral Infarction, run by ReNeuron Limited at 9 sites in United Kingdom.
Trial summary
The primary aim of this Phase II trial is to determine whether it is sufficiently likely that CTX DP treatment at a dose level of 20 million cells improves the recovery in the use of the paretic arm in acute stroke patients to justify a subsequent larger prospectively controlled study. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Ischaemic Stroke, Cerebral Infarction, Hemiparesis
- What is being tested?
- CTX DP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 9 sitesUnited Kingdom
- Study dates
- Jun 2014to 16 Aug 2017
- 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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent or witnessed informed consent in the event that the patient is unable to sign informed consent due to paresis of the affected arm.
- Supratenorial ishaemic stroke
- Male or female aged 40 years or more.
- Stroke, at time of consent, satisfying the following criteria:
- Modified NIHSS Motor Arm Score of 2, 3 or 4 for affected arm visit 1 and visit 2.
- Clinical diagnosis of stroke confirmed by physician using neuro-imaging (CT or MRI).
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- A Score of 0 or 1 for test 2 of the ARAT on day 28+7 and day 56+7 post-stroke using the affected arm.
- Ability to comprehend verbal commands.
- Eligible for neurosurgery including appropriate anatomical target for cell implantation.
Who cannot join
- - Prior history of stroke resulting in permanent moderate to severe disability (i.e. Rankin Scale greater than 2) (other than the presenting ischaemic stroke).
- Stroke due to haemorrhage.
- History of neurological or other disease resulting in significant functional impairment of the paretic arm impairing potential ability to pick up, lift and place a 2.5 cm3 block (e.g. Parkinson's disease, motor neuron disease, arthritis, Dupuytren's contracture or fixed anatomical abnormality).
- Any contraindications to MRI including presence of a cardiac pacemaker (excluding MR-conditional cardiac pacemaker), metal fragments in eye etc.
- Uncontrolled blood pressure defined as systolic blood pressure ≥180 mm Hg or diastolic blood pressure ≥110 mm Hg (patients are only to be excluded if an initial value exceeding these limits is repeated on retesting over several days).
- Patient with a severe comorbid disorder, not expected to survive more than 12 months.
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- Acute cardiovascular events other than the presenting ischaemic stroke (e.g. myocardial infarction, recent coronary intervention for symptomatic cardiac disease) considered by the Investigator or the anaesthetist responsible for the patient to place the patient at increased anaesthetic risk, 3 months prior to planned injection of CTX0E03 DP.
- History of malignant disease (except for non-melanoma skin cancer) within the previous 5 years or any history of malignant brain tumours or brain metastasis.
- Current treatment with tamoxifen.
- Patients taking valproate drugs for any indication in whom it is not considered appropriate to discontinue the valproate for a period of one week prior and four weeks post neurosurgery. Patients in whom valproate is switched to an alternative agent during this period may be included.
- Requirement for antiplatelets and/or anticoagulants including heparin, warfarin or other anticoagulants/ medication that can not be interrupted to allow surgery.
- Requirement for intermittent (stop/start date from 1-month prior-to and 3 month post- CTX0E03 DP administration) use of oral antispasticity medications (oral antispasticity medications are acceptable if they have been taken regularly for at least one month prior to CTX0E03 DP administration).
- A history of uncontrolled diabetes e.g. history of hypoglycaemic or hyperglycaemic events requiring hospital admission over previous 6 months.
- Females of childbearing potential (FOCBP) (or within 2 years of last menstrual cycle) must have a confirmed negative pregnancy test at time of treatment and agree to use two reliable methods of contraception (e.g. oral contraceptive and condom, intra-uterine device (IUD) and condom, diaphragm with spermicide and condom) for the duration of this study
- Sexually active males with partners who are FOCBP must be willing to use a reliable method of contraception (e.g. barrier and spermicide or as described above) for the duration of this study.
- Considered unlikely to be able to attend for all follow-up visits.
- Organ transplant recipient
- In the opinion of the investigator, sustained consumption of alcohol or drugs at a level likely to be injurious to health.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United Kingdom9 sites
Queen Elizabeth Hospital
Birmingham
NHS Southern General Hospital
Glasgow, G51 4TF
Kings College Hospital
London
University College London Hospital
London
Royal Victoria Infirmary
Newcastle
Nottingham City Hospital
Nottingham
SalfordRoyal NHS Foundation Trust
Salford
Royal Hallamshire Hosptial
Sheffield
Southampton Hospital
Southampton
About this study
Official title: A Phase II Efficacy Study of Intracerebral CTX0E03 DP in Patients With Stable Paresis of the Arm Following an Ischaemic Stroke.
The primary aim of this Phase II trial is to determine whether it is sufficiently likely that CTX DP treatment at a dose level of 20 million cells improves the recovery in the use of the paretic arm in acute stroke patients to justify a subsequent larger prospectively controlled study.
This study will evaluate the safety and efficacy of intracerebral CTX DP at a dose level of 20 million cells in patients with paresis of an arm following an ischaemic middle cerebral artery (MCA) stoke. Eligible patients will have no useful function of the paretic arm a minimum of 28 days after the ischaemic stroke (a modified NIH Stroke Scale (NIHSS) Motor Arm Score of 2, 3 or 4 for the affected arm).
Read the detailed description
Design: This Phase II efficacy trial is a multi-centre, open label, single arm, non-comparative design, administering a single dose of CTX cells 2 to 3 months post-ischaemic stroke with follow-up over 12 months. The trial will be overseen by an independent DSMB. The DSMB will adjudicate at predetermined intervals whether a patient has satisfied the primary response criterion and whether the ongoing safety profile justifies continuation or modification of the study.
At least 21 patients will be enrolled to receive CTX DP (20 million cells) by stereotaxic intra-striatal injection ipsilateral to the location of the MCA ischaemic stroke.
Pre-treatment selection of patients: Men and women, aged 40 or more, supratentorial ischaemic stroke or a stroke with elements of both in an area perfused by the MCA (i.e. stroke due to ischaemia resulting in infarct located in the basal ganglia, internal capsule, or corona radiata or a stroke due to ischaemia resulting in infarction of part of the cerebral cortex).
Patients with a first stroke within the past 4 weeks (at time of consent) satisfying the following criteria: Modified NIHSS Motor Arm Score of 2 (some effort against gravity), 3 (no movement against gravity) or 4 (no movement) for the paretic arm post ischaemic stroke; Clinical diagnosis of stroke confirmed by physician using neuro-imaging (computerised tomography or magnetic resonance imaging). A Score of 0 or 1 for test 2 of the ARAT at visit 1 and 2 using the affected arm.
Treatment: One patient will be treated at one time. A single dose (20 million) of CTX DP cells will be administered intracranially via stereotaxic neurosurgery.
Post-treatment follow-up: Patients will be followed for 12 months post-implantation.
End-points: The primary endpoint of the trial is efficacy, using ARAT. Secondary endpoints are efficacy and safety. Outcome measures for efficacy include Fugl-Meyer, NIHSS, BI and RFA. Safety will be assessed by incidence of relevant adverse events monitoring patient's general physical condition and clinical measures (temperature, pulse rate and rhythm, ECG, blood pressure, full blood count, liver function tests, serum urea and electrolytes), immunological response and concomitant medications at the 7 follow-up visits to the clinic in the first year after treatment.
Post-trial follow-up: Annual correspondence with family practitioners; Life-long follow-up for new diagnosis of cancer, site of primary tumour, and survival via National Cancer Registry.
- Conditions
- Ischaemic Stroke, Cerebral Infarction, Hemiparesis, Arm Paralysis
- Being tested
- CTX DP
- Keywords
- Efficacy, Non comparative, Neural stem cells, Intracranial administration
- Medical subject headings
- Ischemic Stroke, Cerebral Infarction, Paresis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CTX DPBiological
Also called CTX0E03 DP, allogeneic human neural stem cell therapy product
20 million cell dose administered by surgery to the damaged area of the brain
| Study group | Role | What they receive |
|---|---|---|
| allogeneic human neural stem cell | Experimental | CTX DP
human neural stem cell product, single dose once only injection Receives: Biological: CTX DP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Action Research Arm Test (ARAT)
The primary outcome measure is a minimum 2 point improvement in the ARAT test number 2 (Yozbatiran et al., 2008).
Response will be defined as a minimum improvement of 2 points in test number 2 of the ARAT (Grasp a 2.5 cm3 block and move it from the starting position to the target end position) in the affected arm 6 months after injection of CTX DP. This would represent an improvement from a pre-treatment state in which the patient was unable to grasp and reposition the block as required to a post-treatment state in which the patient could accomplish the task as specified within 60 seconds.
Measured: 3 months
Secondary outcomes (6)
To assess the efficacy of intracranial CTX DP in restoring upper limb function following an ischaemic stroke using the ARAT
Measured: 12 months
To assess the efficacy of intracranial CTX DP in restoring function following an ischaemic stroke using the Modified National Institutes of Health Stroke Scale (NIHSS)
Measured: 12 months
To assess the efficacy of intracranial CTX DP in restoring patient's functional independence following an ischaemic stroke using the Rankin Focused Assessment (RFA) version of the modified Rankin Scale
Measured: 12 months
To assess the efficacy of CTX DP in improving patient's ability to execute activities of daily living following an ischaemic stroke using the Barthel Index (BI)
Measured: 12 months
To assess the safety and tolerability of intracranial CTX DP in patients following an ischaemic stroke
Incidence of adverse events: monitoring of vital signs, temperature, pulse rate and rhythm, ECG, blood pressure, full blood count, liver function test, serum urea and electrolytes, CTX antibody screen
Measured: 12 months
To assess the efficacy of intracranial CTX DP in restoring upper limb function following an ischaemic stroke using the Fugl-Meyer
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 posted21 Apr 2014 (estimated)
- Study startJun 2014
- Primary completion31 Oct 2016
- Study completion16 Aug 2017
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 Ischaemic 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- ReNeuron Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Keith W Muir, Principal investigator, University of Glasgow
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02117635
- Sponsor's protocol ID
- RN01-CP-0002
- Other IDs
- 2012-003482-18
- Acronym
- PISCES-II
- Status last verified
- Apr 2018
- First submitted
- 16 Apr 2014
- Last updated
- 23 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Yozbatiran N, Der-Yeghiaian L, Cramer SC. A standardized approach to performing the action research arm test. Neurorehabil Neural Repair. 2008 Jan-Feb;22(1):78-90. doi: 10.1177/1545968307305353. Epub 2007 Aug 17.
PubMed 17704352Stevanato L, Thanabalasundaram L, Vysokov N, Sinden JD. Investigation of Content, Stoichiometry and Transfer of miRNA from Human Neural Stem Cell Line Derived Exosomes. PLoS One. 2016 Jan 11;11(1):e0146353. doi: 10.1371/journal.pone.0146353. eCollection 2016.
PubMed 26752061Stevanato L, Hicks C, Sinden JD. Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes. J Vis Exp. 2015 Apr 12;(98):52410. doi: 10.3791/52410.
PubMed 25938519
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Efficacy Study of Intracerebral CTX0E03 DP in Patients With Stable Paresis of the Arm Following an Ischaemic Stroke.
- ClinicalTrials.gov ID
- NCT02117635
- Acronym / sponsor ID
- PISCES-II / RN01-CP-0002
- Conditions
- Ischaemic Stroke, Cerebral Infarction, Hemiparesis, Arm Paralysis
- Keywords
- Efficacy, Non comparative, Neural stem cells, Intracranial administration
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- ReNeuron LimitedIndustry (pharma, biotech, devices)
- Study start
- Jun 2014
- Primary completion
- 31 Oct 2016 (actual)
- Study completion
- 16 Aug 2017 (actual)
- First posted
- 21 Apr 2014 (estimated)
- 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.
The primary aim of this Phase II trial is to determine whether it is sufficiently likely that CTX DP treatment at a dose level of 20 million cells improves the recovery in the use of the paretic arm in acute stroke patients to justify a subsequent larger prospectively controlled study.
This study will evaluate the safety and efficacy of intracerebral CTX DP at a dose level of 20 million cells in patients with paresis of an arm following an ischaemic middle cerebral artery (MCA) stoke. Eligible patients will have no useful function of the paretic arm a minimum of 28 days after the ischaemic stroke (a modified NIH Stroke Scale (NIHSS) Motor Arm Score of 2, 3 or 4 for the affected arm).
Detailed description
Design: This Phase II efficacy trial is a multi-centre, open label, single arm, non-comparative design, administering a single dose of CTX cells 2 to 3 months post-ischaemic stroke with follow-up over 12 months. The trial will be overseen by an independent DSMB. The DSMB will adjudicate at predetermined intervals whether a patient has satisfied the primary response criterion and whether the ongoing safety profile justifies continuation or modification of the study.
At least 21 patients will be enrolled to receive CTX DP (20 million cells) by stereotaxic intra-striatal injection ipsilateral to the location of the MCA ischaemic stroke.
Pre-treatment selection of patients: Men and women, aged 40 or more, supratentorial ischaemic stroke or a stroke with elements of both in an area perfused by the MCA (i.e. stroke due to ischaemia resulting in infarct located in the basal ganglia, internal capsule, or corona radiata or a stroke due to ischaemia resulting in infarction of part of the cerebral cortex).
Patients with a first stroke within the past 4 weeks (at time of consent) satisfying the following criteria: Modified NIHSS Motor Arm Score of 2 (some effort against gravity), 3 (no movement against gravity) or 4 (no movement) for the paretic arm post ischaemic stroke; Clinical diagnosis of stroke confirmed by physician using neuro-imaging (computerised tomography or magnetic resonance imaging). A Score of 0 or 1 for test 2 of the ARAT at visit 1 and 2 using the affected arm.
Treatment: One patient will be treated at one time. A single dose (20 million) of CTX DP cells will be administered intracranially via stereotaxic neurosurgery.
Post-treatment follow-up: Patients will be followed for 12 months post-implantation.
End-points: The primary endpoint of the trial is efficacy, using ARAT. Secondary endpoints are efficacy and safety. Outcome measures for efficacy include Fugl-Meyer, NIHSS, BI and RFA. Safety will be assessed by incidence of relevant adverse events monitoring patient's general physical condition and clinical measures (temperature, pulse rate and rhythm, ECG, blood pressure, full blood count, liver function tests, serum urea and electrolytes), immunological response and concomitant medications at the 7 follow-up visits to the clinic in the first year after treatment.
Post-trial follow-up: Annual correspondence with family practitioners; Life-long follow-up for new diagnosis of cancer, site of primary tumour, and survival via National Cancer Registry.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| allogeneic human neural stem cell | Experimental | Biological: CTX DPCTX DP human neural stem cell product, single dose once only injection |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Written informed consent or witnessed informed consent in the event that the patient is unable to sign informed consent due to paresis of the affected arm.
- Supratenorial ishaemic stroke
- Male or female aged 40 years or more.
- Stroke, at time of consent, satisfying the following criteria:
- Modified NIHSS Motor Arm Score of 2, 3 or 4 for affected arm visit 1 and visit 2.
Key exclusion criteria (18 listed)
- - Prior history of stroke resulting in permanent moderate to severe disability (i.e. Rankin Scale greater than 2) (other than the presenting ischaemic stroke).
- Stroke due to haemorrhage.
- History of neurological or other disease resulting in significant functional impairment of the paretic arm impairing potential ability to pick up, lift and place a 2.5 cm3 block (e.g. Parkinson's disease, motor neuron disease, arthritis, Dupuytren's contracture or fixed anatomical abnormality).
- Any contraindications to MRI including presence of a cardiac pacemaker (excluding MR-conditional cardiac pacemaker), metal fragments in eye etc.
- Uncontrolled blood pressure defined as systolic blood pressure ≥180 mm Hg or diastolic blood pressure ≥110 mm Hg (patients are only to be excluded if an initial value exceeding these limits is repeated on retesting over several days).
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 |
|---|---|---|
| CTX DPAlso: CTX0E03 DP, allogeneic human neural stem cell therapy product20 million cell dose administered by surgery to the damaged area of the brain | Biological | allogeneic human neural stem cell |
Primary outcome
Action Research Arm Test (ARAT)
Time frame: 3 months
The primary outcome measure is a minimum 2 point improvement in the ARAT test number 2 (Yozbatiran et al., 2008). Response will be defined as a minimum improvement of 2 points in test number 2 of the ARAT (Grasp a 2.5 cm3 block and move it from the starting position to the target end position) in the affected arm 6 months after injection of CTX DP. This would represent an improvement from a pre-treatment state in which the patient was unable to grasp and reposition the block as required to a post-treatment state in which the patient could accomplish the task as specified within 60 seconds.
6 secondary outcomes
To assess the efficacy of intracranial CTX DP in restoring upper limb function following an ischaemic stroke using the ARAT
Time frame: 12 months
To assess the efficacy of intracranial CTX DP in restoring function following an ischaemic stroke using the Modified National Institutes of Health Stroke Scale (NIHSS)
Time frame: 12 months
To assess the efficacy of intracranial CTX DP in restoring patient's functional independence following an ischaemic stroke using the Rankin Focused Assessment (RFA) version of the modified Rankin Scale
Time frame: 12 months
To assess the efficacy of CTX DP in improving patient's ability to execute activities of daily living following an ischaemic stroke using the Barthel Index (BI)
Time frame: 12 months
To assess the safety and tolerability of intracranial CTX DP in patients following an ischaemic stroke
Time frame: 12 months
To assess the efficacy of intracranial CTX DP in restoring upper limb function following an ischaemic stroke using the Fugl-Meyer
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2018.
- Background: PubMed 17704352Yozbatiran N, Der-Yeghiaian L, Cramer SC. A standardized approach to performing the action research arm test. Neurorehabil Neural Repair. 2008 Jan-Feb;22(1):78-90. doi: 10.1177/1545968307305353. Epub 2007 Aug 17.
- Derived from this study: PubMed 26752061Stevanato L, Thanabalasundaram L, Vysokov N, Sinden JD. Investigation of Content, Stoichiometry and Transfer of miRNA from Human Neural Stem Cell Line Derived Exosomes. PLoS One. 2016 Jan 11;11(1):e0146353. doi: 10.1371/journal.pone.0146353. eCollection 2016.
- Derived from this study: PubMed 25938519Stevanato L, Hicks C, Sinden JD. Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes. J Vis Exp. 2015 Apr 12;(98):52410. doi: 10.3791/52410.
- The PISCES safety trial is designed to test the safety of a manufactured neural stem cell line (CTX cells) delivered by injection into the damaged brains of male patients 60 years or over who are moderately to severely disabled 6-60 months post-stroke.Link provided by the sponsor.
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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.
Keith W Muir principal investigator
University of Glasgow
9 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 CTX DP in people with Ischaemic Stroke and Cerebral Infarction, run by ReNeuron Limited at 9 sites in United Kingdom.
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 9 inclusion and 18 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: finished, as of the sponsor's last update on 23 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United Kingdom. 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. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Action Research Arm Test (ARAT) (time frame: 3 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 NCT02117635, 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 23 Jul 2018.