Stroke MedDRA version: 14.0 Level: LLT Classification code 10023027 Term: Ischaemic stroke NOS System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: GSK249320
Product Code: GSK249320
Pharmaceutical Form: Solution for infusion
Current Sponsor code: GSK249320
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
C
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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. 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 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. 4. Have a total NIHSS score of 3-21. 5. 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). 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. 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. 10. In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 360 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 360
Exclusion criteria
Exclusion criteria: 1. Ability to walk >0.8m/s as measured by the Gait Velocity assessment. 2. History of a previous symptomatic stroke within 3 months prior to study entry. 3. Presence of significant disability prior to the current stroke. Significant disability is defined as having a pre-stroke Rankin score of >2. 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 a significant pre-existing gait deficit prior to study entry that is likely to confound clinical evaluations 7. 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. 8. The subject poses a significant suicide risk, in the opinion of the investigator. 9. 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. 10. Presence of either a central or peripheral demyelinating disease, such as multiple sclerosis or IgM monoclonal gammopathy of unknown significance (MGUS). 11. 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. 12. Presence of the following ECG values on baseline ECG: QTc > 500 msec; or uncorrected QT >600msec (machine or manual over-read). 13. Participation in any investigational rehabilitation paradigm targeting stroke recovery during the duration of this study. 14. 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). 15. Prior treatment with GSK249320. 16. History of sensitivity to Investigational Product excipients that, in the opinion of the investigator or GSK Medical Monitor, contraindicates the subject's participation. 17. Pregnant females as determined by positive urine hCG test prior to enrollment. 18. Lactating females. 19. Subjects considered unwilling or unable to comply with the procedures and study visit schedule outlined in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • To further demonstrate and characterize the extent and duration of overall motor recovery (i.e., locomotion, balance, number of falls, dexterity, strength and endurance) after treatment with GSK249320 or placebo in ischemic stroke patients • To evaluate the safety and tolerability of GSK249320 in comparison to placebo in ischemic stroke patients • To further characterize the immunogenicity profile of GSK249320 in ischemic stroke patients • To further characterize the pharmacokinetic (PK) profile of GSK249320 in ischemic stroke patients;Main Objective: • To assess the efficacy of GSK249320 versus placebo on lower limb motor recovery, specifically locomotion, in ischemic stroke patients;Primary end point(s): Primary efficacy Endpoints: Mean change from baseline to Month 3/Day 90 in Gait Velocity .;Timepoint(s) of evaluation of this end point: Day 1, Month 1, 2, 3 and 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy Endpoints: • Mean change from baseline to Month 6/Day 180 in Gait Velocity • Proportion of subjects transitioning from one category of gait velocity to the next higher category (0, >0 to 0.8m/s) • Mean change from baseline to Month3/Day 90 and mean change from baseline to Month 6/Day 180 in: • Balance as measured by the Berg Balance total score • Dexterity as measured by Box and Blocks test (number of blocks transferred in 60 seconds) • Strength as measured by grip and knee extension dynamometry (kilograms and pounds, respectively) • Proportion of subjects experiencing falls and the number of falls between Baseline to Month 3/Day 90 and to Month 6/Day 180. • Mean change from Month 1/Day 30 to Month 3/Day 90 in endurance as measured by distance travelled in meters during the 2 Minute Walk Test. Safety Endpoints • Type and incidence of adverse events (AEs) and Events Common to Stroke (ECtS) • Change from baseline in vital signs (blood pressure and heart rate) and electrocardiogram (ECG) parameters • Change from baseline in chemistry and hematology safety labs • Change from baseline in the NIHSS • Prospective assessment of suicidality via Columbia Suicide Severity Rating Scale (C-SSRS) PK, PD Marker and Immunogenicity Endpoints: • The following PK parameters will be estimated, when feasible: Cmax, tmax, half life, AUC(0-), AUC(0-inf) clearance and volume of distribution. Age, gender, race, and weight will be tested as covariates on clearance and volume of distribution. • Selected PD assays of target engagement, will be performed. Other PD markers may be tested to further characterise the PD effects of GSK249320. • Antibodies against GSK249320 will be assessed using immunoelectrochemiluminescent (ECL) assays;Timepoint(s) of evaluation of this end point: Day 1, Month 1, 2, 3 and 6 | — |
Countries
Australia, Belgium, Canada, Czech Republic, Denmark, France, Germany, Italy, United Kingdom, United States
Contacts
Public ContactClincial Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed