Trial record 2 of 90 for:    stem cells in stroke

Pilot Investigation of Stem Cells in Stroke Phase II Efficacy (PISCES-II)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by ReNeuron Limited
Sponsor:
Information provided by (Responsible Party):
ReNeuron Limited
ClinicalTrials.gov Identifier:
NCT02117635
First received: April 16, 2014
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

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).


Condition Intervention Phase
Ischaemic Stroke
Cerebral Infarction
Hemiparesis
Arm Paralysis
Biological: CTX DP
Phase 2

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by ReNeuron Limited:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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


Estimated Enrollment: 41
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)
Arms Assigned Interventions
Experimental: allogeneic human neural stem cell

CTX DP

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
Other Names:
  • CTX0E03 DP
  • allogeneic human neural stem cell therapy product

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   40 Years to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • Subcortical or cortical ischaemic stroke or a stroke with elements of both in an area perfused by the middle cerebral artery (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).
  • Male or female.
  • Age 40 to 89 years old inclusive.
  • First stroke within the past 4 weeks (at time of consent) satisfying the following criteria:
  • Modified NIHSS Motor Arm Score of 2 or 3 for affected arm on day 28+7 and day 56+7 post-stroke.
  • 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. No medical conditions which would preclude neurosurgery with appropriate preparation and management.

Exclusion criteria:

  • Prior history of stroke resulting in permanent moderate to severe disability (i.e. Rankin Scale greater than 2) (other than the presenting ischaemic stroke).
  • NIHSS upper limb = 4.
  • 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, 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) 3 months prior to planned injection of CTX DP.
  • History of malignant disease, other than basal-cell carcinoma, cervical carcinoma in situ, superficial bladder cancer or successfully treated adolescent leukaemias or cancers.
  • Current treatment with tamoxifen.
  • Patients taking sodium valproate for any indication in whom it is not considered appropriate to discontinue the valproate for a period of 1 week prior and 4 weeks post neurosurgery. Patients in whom valproate is switched to an alternative agent during this period may be included.
  • Documented fever within 7 days of the planned surgical procedure.
  • HbA1c <8.0%; (<64mmol/mol).
  • Women less than 2 years of post last menstrual period unless with a history of surgical sterilisation. (Women greater than 2 years but less than 4 years since their last menstrual period must have a negative pregnancy test).
  • Considered unlikely to be able to attend for all follow-up visits.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02117635

Locations
United Kingdom
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         
Sponsors and Collaborators
ReNeuron Limited
Investigators
Principal Investigator: Keith W Muir University of Glasgow
  More Information

Additional Information:
Publications:
Responsible Party: ReNeuron Limited
ClinicalTrials.gov Identifier: NCT02117635     History of Changes
Other Study ID Numbers: RN01-CP-0002, 2012-003482-18
Study First Received: April 16, 2014
Last Updated: June 3, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by ReNeuron Limited:
Efficacy
Non comparative
Neural stem cells
Intracranial administration

Additional relevant MeSH terms:
Cerebral Infarction
Stroke
Paresis
Infarction
Ischemia
Paralysis
Brain Infarction
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Neurologic Manifestations
Signs and Symptoms
Pathologic Processes
Necrosis

ClinicalTrials.gov processed this record on August 26, 2014