Pilot Investigation of Stem Cells in Stroke Phase II Efficacy

NCT02117635 | Completed Phase 2 DMC

• 2 other identifiers: RN01-CP-00022012-003482-18
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 9

Brief 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. 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).

Conditions

Ischaemic Stroke; Cerebral Infarction; Hemiparesis; Arm Paralysis

Keywords

Efficacy; Non comparative; Neural stem cells; Intracranial administration

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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)

  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

  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)

  12 months

• To assess the safety and tolerability of intracranial CTX DP in patients following an ischaemic stroke

  12 months

Study Arms (1)

allogeneic human neural stem cell

EXPERIMENTAL

CTX DP human neural stem cell product, single dose once only injection

Biological: CTX DP

Interventions

CTX DP BIOLOGICAL

20 million cell dose administered by surgery to the damaged area of the brain

Also known as: CTX0E03 DP, allogeneic human neural stem cell therapy product

allogeneic human neural stem cell

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• \- 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.
• 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.

Sponsors & Collaborators

• ReNeuron Limited: lead

Study Sites (9)

Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

NHS Southern General Hospital

Glasgow, G51 4TF, United Kingdom

Location

Kings College Hospital

London, United Kingdom

Location

University College London Hospital

London, United Kingdom

Location

Royal Victoria Infirmary

Newcastle, United Kingdom

Location

Nottingham City Hospital

Nottingham, United Kingdom

Location

SalfordRoyal NHS Foundation Trust

Salford, United Kingdom

Location

Royal Hallamshire Hosptial

Sheffield, United Kingdom

Location

Southampton Hospital

Southampton, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 17704352 BACKGROUND

• Stevanato 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.

  PMID: 26752061 DERIVED

• Stevanato 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.

  PMID: 25938519 DERIVED

Related Links

• 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.

MeSH Terms

Conditions

Ischemic Stroke; Cerebral Infarction; Paresis

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Infarction; Brain Ischemia; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Keith W Muir

  University of Glasgow

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2014
• First Posted: April 21, 2014
• Study Start: June 1, 2014
• Primary Completion: October 31, 2016
• Study Completion: August 16, 2017
• Last Updated: July 23, 2018

Record last verified: 2018-04

Locations

GB (9)