Supratentorial ischaemic stroke MedDRA version: 20.0 Level: PT Classification code 10061256 Term: Ischaemic stroke System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: CTX0E03 Drug Product (DP)
Product Code: CTX0E03
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: CTX0E03 human neural st
Sponsors
ReNeuron Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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. 2. Supratentorial ischaemic stroke. 3. Male or female. 4. Age 40 years or more. 5. Stroke, at time of consent, satisfying the following criteria: • Modified NIH Stroke Scale (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 at visit 1 and 2. • 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 Action Research Arm Test (Grasp a 2.5 cm3 block and move it from the starting position to the target end position) at visit 1 and 2 post-stroke using the affected arm. 6. Ability to comprehend verbal commands. 7. Eligible for neurosurgery, including appropriate anatomical target for cell implantation. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
Exclusion criteria: 1. Prior history of stroke resulting in permanent moderate to severe disability (i.e. Rankin Scale greater than 2) (other than the presenting ischaemic stroke). 2. Stroke due to haemorrhage. 3. 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). 4. Any contraindications to MRI including presence of a cardiac pacemaker (excluding MR-conditional cardiac pacemaker), metal fragments in eye etc. 5. 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). 6. Patient with a severe comorbid disorder, not expected to survive more than 12 months. 7. 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. 8. 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. 9. Current treatment with tamoxifen. 10. 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. 11. Requirement for antiplatelets and/or anticoagulants including heparin, warfarin or other anticoagulants/ medication that cannot be interrupted to allow surgery. 12. 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). 13. A history of uncontolled diabetes e.g. history of hypoglycaemic or hyperglycaemic events requiring hospital admission over previous 6 months. 14. 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. 15. 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. 16. Considered unlikely to be able to attend for all follow-up visits. 17. Organ transplant recipient. 18. In the opinion of the Investigator, sustained consumption of alcohol or drugs at a level likely to be injurious to health
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 3 months following the single dose drug treatment.; Main Objective: • To determine whether a sufficient proportion of patients experience response of their paretic arm following treatment with CTX0E03 DP at a dose level of 20 million cells to justify a subsequent randomised study. o Response will be defined as a minimum improvement of 2 points in test number 2 of the Action Research Arm Test (Grasp a 2.5 cm3 block and move it from the starting position to the target end position) in the affected arm 3 months after injection of CTX0E03 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 and would represent recovery of useful function in a previously paretic arm. ; Secondary Objective: • To assess the efficacy of i.c. CTX0E03 DP in restoring upper limb function following an ischaemic stroke using the Action Research Arm Test (ARAT). • To assess the efficacy of i.c. CTX0E03 DP in restoring function following an ischaemic stroke using the National Institutes of Health Stroke Scale (NIHSS). • To assess the efficacy of i.c. CTX0E03 DP in restoring patient’s functional independence following an ischaemic stroke using the Rankin Focused Assessment (RFA) version of the Modified Rankin Scale (mRS). • To assess the efficacy of i.c. CTX0E03 DP in improving patient’s ability to execute activities of daily living following an ischaemic stroke using the Barthel Index (BI). • To assess the efficacy of i.c. CTX0E03 DP in sensorimotor recovery of the affected limb following an ischaemic stroke using the Fugl-Meyer Assessment (FMA). • To assess the safety and tolerability of i.c. CTX0E03 DP in patients follow | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To assess the efficacy of intracranial CTX0E03 DP in restoring upper limb function following an ischaemic stroke using the Action Research Arm Test (ARAT). • To assess the efficacy of intracranial CTX0E03 DP in restoring function following an ischaemic stroke using the National Institutes of Health Stroke Scale (NIHSS). • To assess the efficacy of intracranial CTX0E03 DP in restoring patient’s functional independence following an ischaemic stroke using the Rankin Focused Assessment (RFA) version of the Modified Rankin Scale (mRS). • To assess the efficacy of intracranial CTX0E03 DP in improving patient’s ability to execute activities of daily living following an ischaemic stroke using the Barthel Index (BI). • To assess the efficacy of intracranial CTX0E03 DP in sensorimotor recovery of the affected limb following an ischaemic stroke using the Fugl-Meyer Assessment (FMA). • To assess the safety and tolerability of intracranial CTX0E03 DP in patients following an ischaemic stroke. ;Timepoint(s) of evaluation of this end point: Periodically up to 12 months following the single dose drug treatment. | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trials Information
ReNeuron Ltd
Outcome results
None listed