Pilot Investigation of Stem Cells in Stroke Phase II Efficacy (PISCES-II)
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 or 3 for the affected arm).
Biological: CTX DP
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Simon Two-Stage Efficacy Study of Intracerebral CTX0E03 DP in Patients With Stable Paresis of the Arm Following an Ischaemic Stroke.|
- Action Research Arm Test (ARAT) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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.
If 2 or more patients satisfy the primary response criterion 6 months after treatment with CTX DP in 1st stage, the study will progress to the 2nd stage and enrolment will be increased to 41 patients. If after 21 patients, fewer than 2 patients satisfy the primary response 6 months after CTX DP treatment, no further patients will be enrolled and the trial will be concluded.
- To assess the efficacy of intracranial CTX DP in restoring upper limb function following an ischaemic stroke using the ARAT [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- To assess the safety and tolerability of intracranial CTX DP in patients following an ischaemic stroke [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]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
|Study Start Date:||June 2014|
|Estimated Study Completion Date:||June 2017|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: allogeneic human neural stem cell
human neural stem cell product, single dose once only injection
Biological: CTX DP
20 million cell dose administered by surgery to the damaged area of the brain
Design: This Phase II efficacy trial is a multi-centre, open label, single arm, non-comparative two stage 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 whether a patient has satisfied the primary response criterion and whether the ongoing safety profile justifies continuation or modification of the study.
In stage 1, up to 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. If 2 or more patients satisfy the primary response criterion 6 months after treatment with CTX DP, the study will progress to Stage 2 and, subject to the agreement of the DSMB, enrolment will be increased to a maximum total of 41 patients.
Pre-treatment selection of patients: Men and women, aged 40 to 89 inclusive, subcortical or cortical 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). Treatment will be offered to eligible women with a history of surgical sterilisation or who are greater than 2 years but less than 4 years since their last menstrual period.
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) or 3 for affected arm (no movement against gravity) on day 28 and day 56 post-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 on day 28 and day 56 post-stroke using the affected arm.
Treatment: One patient will be treated at one time. A single dose (20 million) of CTX 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 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02117635
|NHS Southern General Hospital||Recruiting|
|Glasgow, United Kingdom, G51 4TF|
|Contact: Keith W Muir, MD, FRCP Keith.Muir@glasgow.ac.uk|
|Principal Investigator: Keith W Muir, MD, FRCP|
|Principal Investigator:||Keith W Muir||University of Glasgow|