Proof of Concept (POC) in Patients With Ischaemic Stroke
Condition: Cerebrovascular Accident
MeSH terms: Stroke
Intervention: GSK249320 100/mg; Placebo
Intervention description: Clear to opalescent, colorless to pale yellow or pale brown, and is supplied as a sterile, concentrated solution (1000mg/vial). GSK249320 is for IV use only.; Placebo is a clear, colorless solution (50mM acetate buffer, pH 5.5 containing 0.02% (w/v) polysorbate-80 and made isotonic with 111.2 mM sodium chloride). Placebo is for intravenous (IV) use only.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 134.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Ischemic Stroke

Summary:

      Study MAG104615, a Proof of Concept Study for GSK249320 versus placebo in Stroke Patients.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have a confirmed diagnosis of stroke according to the World Health Organization
             definition which is, 'a rapid onset event of vascular origin reflecting a focal
             disturbance of cerebral function, excluding isolated impairments of higher function,
             and persisting longer than 24 hours [World Health Organization, 1989].

          -  Stroke onset must be within the last 24-72 hours of the first infusion of
             Investigational Product. Time of stroke onset is defined at the time at which the
             patient/relative is first aware of the stroke deficit. For patients who awake with
             deficits, or who are found unconscious, the time of onset is defined as the time at
             which they were last known to be symptom free.

          -  Have a stroke that is radiologically confirmed to be ischemic and supratentorial. The
             diameter of the ischemic lesion is >15mm in any single direction or the volume is
             >4cc. See the Study Procedures Manual (SPM) for guidance on how to calculate the
             lesion size.

          -  Have a total NIHSS score of 3-21.

          -  Have a lower limb deficit from the incident stroke which is defined as a score of 1-4
             on the NIHSS Motor Leg question (question #6).

          -  Aged 18-90, inclusive.

          -  Expectation the subject will receive standard physical, occupational and speech
             rehabilitation therapy as indicated for the post stroke deficits.

          -  Male subjects and female subjects of non-child-bearing and child-bearing potential are
             allowed to participate in this study. See Section 11, Appendix 1 for definitions.
             Females of child-bearing potential must have a negative pregnancy test prior to
             enrollment and must agree to use one of the contraceptive methods specified in Section
             11, Appendix 1.

        Exclusion Criteria:

          -  Ability to walk >0.8m/s as measured by the Gait Velocity assessment.

          -  History of a previous symptomatic stroke within 3 months prior to study entry.

          -  Presence of significant disability prior to the current stroke. Significant disability
             is defined as having a pre-stroke Rankin score of >2.

          -  Subjects who are not alert or are unresponsive as defined by a score of 2 or 3 on the
             NIHSS Level of Consciousness question (Question 1a).

          -  Presence of significant aphasia likely to confound or interfere with completion of the
             study assessments.

          -  Presence of a significant pre-existing gait deficit prior to study entry that is
             likely to confound clinical evaluations

          -  Presence of pre-existing neurologic or psychiatric disease which is active and not
             adequately controlled such that it interfered with major activities of daily living
             immediately prior to the current stroke and is likely to interfere with study
             participation/visits or confound clinical evaluations.

          -  The subject poses a significant suicide risk, in the opinion of the investigator.

          -  Current or chronic history of liver disease, known hepatic or biliary abnormalities
             (except Gilbert's syndrome or asymptomatic gallstones), or known history of hepatitis
             B or hepatitis C infection. A positive hepatitis B or hepatitis C result on the GSK
             labs drawn at baseline/Study Day 1 do not exclude a subject from continuing in the
             study unless there are associated clinical signs/symptoms of liver disease; however,
             the subject should be treated as clinically indicated and the GSK Medical Monitor
             should be contacted for further discussion.

          -  Presence of either a central or peripheral demyelinating disease, such as multiple
             sclerosis or IgM monoclonal gammopathy of unknown significance (MGUS).

          -  Expected death due to the incident stroke, or evidence of a chronic co-morbid
             condition or unstable acute systemic illness which, in the opinion of the
             investigator, could shorten the subject's survival such that it would limit his/her
             ability to complete the study.

          -  Presence of the following ECG values on baseline ECG: QTc > 500 msec (using either
             Bazett's formula (QTcB) or Fridericia's formula (QTcF)); or uncorrected QT >600msec
             (machine or manual over-read). If the ECG indicates a prolonged QTc interval value
             outside these limits, two further ECGs should be performed during the same sitting and
             the average QTc value of these triplicate ECGs calculated. If the average value
             exceeds the stated limits, the subject is not eligible.

          -  Participation in any investigational rehabilitation paradigm targeting stroke recovery
             during the duration of this study.

          -  Have a contraindication to MRI as per local hospital practice/guidelines.

          -  The subject has participated in a clinical trial and has received an investigational
             product within the following time period prior to the first dosing day in the current
             study: 30 days, 5 half-lives or twice the duration of the biological effect of the
             investigational product (whichever is longer).

          -  Prior treatment with GSK249320.

          -  History of sensitivity to Investigational Product excipients (acetate buffer,
             polysorbate 80 and sodium chloride) that, in the opinion of the investigator or GSK
             Medical Monitor, contraindicates the subject's participation.

          -  Pregnant females as determined by positive urine hCG test prior to enrollment.

          -  Lactating females.

          -  Subjects considered unwilling or unable to comply with the procedures and study visit
             schedule outlined in the protocol.