Safety Escalating Repeat IV, in Stroke Patients (MAG111539)

GlaxoSmithKline (GSK)

Status and phase

Completed

Phase 2

Conditions

Ischaemic Attack, Transient

Treatments

Drug: GSK249320

Drug: PLACEBO

Study type

Interventional

Funder types

Industry

Identifiers

NCT00833989

111539

Details and patient eligibility

About

The purpose of this study is to is to test increasing repeat doses of GSK249320 compared to placebo in patients with stroke.

Full description

GSK249320 is a humanised monoclonal antibody (mAb) that binds with high specificity to myelin-associated glycoprotein (MAG) and antagonises or neutralises MAG-mediated inhibition and has been shown to improve functional recovery after stroke in pre-clinical models, possibly by promoting neuroregeneration and plasticity. The present study is the first in patients with stroke. The main aim of this study is to select tolerated doses of GSK249320 that can be used in future trials to evaluate its efficacy in improving clinical function in patients recovering from stroke. This clinical trial is designed as a placebo-controlled, single-blind, multicenter study to investigate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of escalating repeat IV doses of GSK249320. Three sequential dose escalation cohorts (1, 5 and 15 mg/kg) are planned, with 8 patients on placebo and 8 on active in cohort 1 and 4 patients on placebo and 8 on active in cohorts 2 and 3. Each patient will receive 2 repeat IV doses 9 ± 1 days apart and assessments will extend to at least 16 weeks.

Enrollment

42 patients

Sex

All

Ages

18 to 90 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Have a confirmed diagnosis of stroke
Stroke onset must be within the last 24-72 hours.
Have a stroke that is either:
radiologically confirmed to be ischaemic and supratentorial. The diameter of the ischemic lesion is >15mm in any singlle direction or the volume is >4cc. OR
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 Hemorrahage (CH) score must be 0-2 and is calculated based on age, Galsgow coma Scale score ad the initial CT or MRI findings for the index stroke. See the SOM for the full calculation procedure.
Have a total NIHSS score of 3-21.
Have an upper and/or lower limb deficit defined as:
Score of 1-3 on the NIHSS Motor Arm question, and palpable and observable voluntary extension or flexion of the fingers. AND/OR b. Score of 1-3 on the NIHSS Motor Leg question
Aged 18-90, inclusive.
Male subjects and females of non-child-bearing potential are allowed to participate in this study.
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 <1%.

Exclusion criteria

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.
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.
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 as likely to confound or interfere with completion of the study assessments.
Presence of peripheral neuropathy, including diabetic neuropathy, which is clinically active and symptomatic at time of screening.
Presence of neurological or psychiatric disease, such as dementia or mild cognitive impairment, prior to study entry that is likely to confound clinical evaluations.
Presence of a demyelinating disease, such as multiple sclerosis.
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.
History of sensitivity to heparin or heparin-induced thrombocytopenia.
Presence of QTcB > 500 msec; or uncorrected QT >600msec (machine or manual over-read) on baseline ECG.
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
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
Participation in any investigational rehabilitation paradigm targeting stroke recovery during the duration of this study.
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).