Patients with Stroke. MedDRA version: 12.1 Level: LLT Classification code 10042244 Term: Stroke
Conditions
Interventions
Product Name: GSK249320
Product Code: GSK249320
Pharmaceutical Form: Intravenous infusion
Current Sponsor code: GSK249320
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Co
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. 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]. 2. Stroke onset must be within the last 24-72 hours. Time of stroke onset is defined as 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. 3. Have a stroke that is either: a. Radiologically confirmed to be ischemic and supratentorial. The diameter of the ischemic lesion is >15mm in any single direction or the volume is >4cc. OR b. Radiologically confirmed to be an intracerebral hemorrhage that is supratentorial, deep (i.e., blood must not directly contact cerebral cortex) and with minimal or no intraventricular extension. The Intracerebral Hemorrhage (ICH) score must be 0-2 and is calculated based on age, Glasgow Coma Scale score and the initial CT or MRI findings for the index stroke. See the SPM for the full calculation procedure. 4. Have a total NIHSS score of 3-21. 5. Have an upper and/or lower limb deficit defined as: a. Score of 1-3 on the NIHSS Motor Arm question (question #5), and palpable and observable voluntary extension or flexion of the fingers. AND/OR b. Score of 1-3 on the NIHSS Motor Leg question (question #6) 6. Aged 18-90, inclusive. 7. Reasonable likelihood of receiving standard physical, occupational and speech rehabilitation therapy as indicated for the post stroke deficits. 8. Reasonable likelihood of receiving both doses of Investigational Product. 9. Be able to provide written and dated informed consent. Where the subject is unable to give consent, consent may be obtained from the subject’s legally authorized representative in accordance with national legislation and local ethics committee guidelines. When able to do so, the subject should be re-consented to continue in the study in the case where the consent was obtained from the legal representative in the first instance. 10. Male subjects and females of non-child-bearing potential are allowed to participate in this study. 11. Females of child-bearing potential are also allowed to participate in this study provided they are using a contraceptive method with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. History of a previous symptomatic stroke within 3 months prior to study entry. 2. Presence of significant disability prior to the current stroke. Significant disability is defined as having a pre-stroke Rankin score of >2. 3. Presence of depression that is active and not adequately controlled such that it interferred with major activities of daily living immediately prior to the current stroke. 4. 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). 5. Presence of significant aphasia likely to confound or interfere with completion of the study assessments. 6. Presence of peripheral neuropathy, including diabetic neuropathy, which is clinically active and symptomatic at time of screening. 7. Presence of neurological or psychiatric disease, such as dementia or mild cognitive impairment, prior to study entry that is likely to confound clinical evaluations 8. Presence of a demyelinating disease, such as multiple sclerosis. 9. Evidence of other chronic co-morbid conditions or unstable acute systemic illnesses which, in the opinion of the investigator, could shorten the subject’s survival or limit his/her ability to complete the study 10. History of sensitivity to heparin or heparin-induced thrombocytopenia. 11. Presence of QTc > 500 msec; or uncorrected QT >600msec (machine or manual over-read) on baseline ECG. If bundle branch block is present, then QTc must not be > 530 msec. 12. Contraindication to TMS, such as: • have metal present, such as hardware or plate on the scalp in the area to which TMS will be applied, implanted cardiac pacemaker, implanted prosthetic heart valve, medication pump or line, metallic implant or clip in the head/neck, electrical, mechanical or magnetic implants, neuro-stimulation device, or orthodontic work involving ferromagnetic materials • occupation or activity that may cause accidental lodging of ferromagnetic materials or embedded metal fragments in the head. Subjects can be cleared by a head computed tomography scan. • concomitant use of drugs that substantially lower seizure threshold (e.g., tricyclic antidepressants and neuroleptics) • known history of seizures or epilepsy • brain tumor, recent brain injury (within 5 years) associated with definite loss of consciousness, or any history of brain surgery • other contraindications per local hospital practice 13. Contraindication to MRI, such as: • have metal present, such as implanted cardiac pacemaker, implanted prosthetic heart valve, medication pump or line, metallic implant or clip in the head/neck, electrical, mechanical or magnetic implants, neuro-stimulation device, or orthodontic work involving ferromagnetic materials, permanent tattooed metallic eye-liner • occupation or activity that may cause accidental lodging of ferromagnetic materials or embedded metal fragments in the head. Subjects can be cleared by a head computed tomography scan. • claustrophobia • other contraindications per local hospital practice 14. Participation in any investigational rehabilitation paradigm targeting stroke recovery during the duration of this study. 15. 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 durat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of two repeat IV doses of GSK249320 in subjects with stroke;Secondary Objective: 1.To evaluate immunogenicity of two repeat IV doses of GSK249320 in subjects with stroke. 2.To evaluate the pharmacokinetics (PK) of two repeat IV doses of GSK249320 in subjects with stroke. 3.To characterize functional and neurophysiological outcome measures in subjects with stroke. 4.To explore any pharmacodynamic (PD) effects of GSK249320 on functional and electrophysiological outcome measures in subjects with stroke. 5. To explore PK-PD relationships between exposure and functional endpoints. 6. To explore the status of blood brain barrier integrity in the study population. 7. To explore the oligodendrocyte protection property of GSK249320. ;Primary end point(s): Adverse events (AEs), vital signs, physical examination (incl. full neurological exam.), 12-lead ECGs, nerve conduction tests (NCTs), magnetic resonance imaging (MRI) and clinical laboratory tests. | — |
Countries
Germany
Outcome results
None listed