Safety Escalating Repeat IV, in Stroke Patients (MAG111539)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00833989
First received: January 29, 2009
Last updated: March 15, 2012
Last verified: October 2011
  Purpose

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


Condition Intervention Phase
Stroke
Ischaemic Attack, Transient
Drug: GSK249320
Drug: PLACEBO
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Official Title: A Single-Blind Study of the Safety, Pharmacokinetics and Pharmacodynamics of Escalating Repeat Doses of GSK249320 in Patients With Stroke

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Presence of antibodies to GSK249320 will be assessed in serum samples using immunoelectro-chemiluminescent (ECL) assay [ Time Frame: At least 16 weeks ] [ Designated as safety issue: No ]
  • PK parameters: AUC(0-), Cmax, Tmax, T1/2 after second dose, clearance, volume of distribution [ Time Frame: At least 16 weeks ] [ Designated as safety issue: No ]
  • Gait velocity, Berg Balance, Fugl-Meyer Motor Assessment, Box and Blocks, grip strength (dynamometer), modified Rankin, Barthel, NIHSS, Transcranial Magnetic Stimulation (TMS), and MRI [ Time Frame: At least 16 weeks ] [ Designated as safety issue: No ]
  • To explore linear or non-linear relationships between exposure parameters and one or a combination of PD endpoints. Possible extension to a disease progression model, if feasible [ Time Frame: At least 16 weeks ] [ Designated as safety issue: No ]
  • Exploratory biomarker levels, such as S100β [ Time Frame: At least 16 weeks ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: July 2009
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: PLACEBO Drug: PLACEBO
Placebo
Experimental: ACTIVE Drug: GSK249320
I.V. infusion

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).

Pregnant or lactating females.

  • Subjects considered unwilling or unable to comply with the procedures and study visit schedule outlined in the protocol.
  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: NCT00833989

Locations
United States, California
GSK Investigational Site
Los Angeles, California, United States, 90095
GSK Investigational Site
Orange, California, United States, 92868-4280
United States, Colorado
GSK Investigational Site
Fort Collins, Colorado, United States, 80524
United States, Michigan
GSK Investigational Site
Detroit, Michigan, United States, 48201
United States, Oregon
GSK Investigational Site
Portland, Oregon, United States, 97239
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H3T 1E2
Germany
GSK Investigational Site
ULM, Baden-wuerttemberg, Germany, 89081
GSK Investigational Site
Celle, Niedersachsen, Germany, 29223
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
GSK Investigational Site
Essen, Nordrhein-westfalen, Germany, 45122
GSK Investigational Site
Leipzig, Sachsen, Germany, 04103
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00833989     History of Changes
Other Study ID Numbers: 111539
Study First Received: January 29, 2009
Last Updated: March 15, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Ischemic Attack, Transient
Stroke
Cerebral Infarction
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction

ClinicalTrials.gov processed this record on August 28, 2014