POC in Patients With Ischaemic Stroke

This study has been terminated.
(This study was terminated for futility.)
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01808261
First received: February 14, 2013
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Cerebrovascular Accident
Drug: GSK249320 100/mg
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Study MAG104615, a Proof of Concept Study for GSK249320 Versus Placebo in Stroke Patients

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change from baseline in gait velocity [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in proportion of subjects transitioning between gait velocity categories [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change from baseline on box and blocks [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Number of falls [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Safety as measured by type and incidence of AEs [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Safety as measured by type and incidence of disease-related events [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Safety as measured by change from baseline in vital signs [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Safety as measured by incidence of abnormal ECG results [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Safety as measured by change from baseline in clinical safety labs [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Safety as measured by change from baseline in NIHSS [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Safety as measured by presence/absence of suicidality via CSSRS [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • PK as measured by maximum observed plasma concentration (Cmax) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • PK as measured by time to reach maximum observed plasma concentration (Tmax) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • PK as measured by plasma decay half-life (t1/2) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • PK as measured by area under the curve from time zero to last quantifiable concentration [AUC (0-t)] [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • PK as measured by area under the curve from time zero to extrapolated infinite time [AUC (0-∞)] [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Antibodies against GSK249320 [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 133
Study Start Date: May 2013
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
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). Both GSK249320 and placebo are for intravenous (IV) use only
Drug: Placebo
Placebo is a clear, colorless
Active Comparator: GSK249320 100/mg
clear to opalescent, colorless to pale yellow or pale brown, and is supplied as a sterile, concentrated solution (1000mg/vial)
Drug: GSK249320 100/mg
clear to opalescent, colorless to pale yellow or pale brown, and is supplied as a sterile, concentrated solution (1000mg/vial)

Detailed Description:

Myelin-associated glycoprotein (MAG) is one of the key proteins known to inhibit neuronal regeneration when released from oligodendrocytes in conditions of neuronal injury, such as stroke. GSK249320 is a humanised monoclonal antibody (mAb) that binds with high specificity to 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 (MAG104615) is designed to establish Proof of Concept (PoC) for GSK249320 in ischemic stroke patients. MAG104615 will be a placebo-controlled, double-blind, multicenter, randomized, repeat dose, Bayesian design study. PoC will be achieved by demonstrating a clinically meaningful improvement in lower limb motor recovery, specifically by evaluating changes in gait velocity from baseline to Day 90/Month 3. Subjects will also be followed out to Day 180/Month 6 to further evaluate longer term motor recovery and safety. Additional secondary efficacy measures of motor recovery will be evaluated to further demonstrate and characterize the extent and duration of overall motor recovery after treatment with GSK249320. Changes in disability and neurological impairment will be characterized after treatment with GSK249320 and explored for how they relate to motor recovery. This PoC study will also further characterize the safety, PK, and immunogenicity of GSK249320 will explore pharmacodynamic (PD) markers, and will explore use of actigraphy to measure motor recovery. Subjects will be stratified by gait velocity at baseline for randomization (1:1 allocation) into one of two treatment groups: 15mg/kg GSK249320, or placebo. Each subject will receive 2 repeat IV doses of GSK249320 or placebo.

  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 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.
  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: NCT01808261

  Hide Study Locations
Locations
United States, California
GSK Investigational Site
Orange, California, United States, 92868-4280
United States, Florida
GSK Investigational Site
Jacksonville, Florida, United States, 32209
United States, Illinois
GSK Investigational Site
Peoria, Illinois, United States, 61637
United States, Kentucky
GSK Investigational Site
Lexington, Kentucky, United States, 40536
United States, Oregon
GSK Investigational Site
Portland, Oregon, United States, 97239
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37232
Canada, Alberta
GSK Investigational Site
Edmonton, Alberta, Canada, T6G 2B7
GSK Investigational Site
Edmonton, Alberta, Canada, T6L 5X8
Canada, Ontario
GSK Investigational Site
London, Ontario, Canada, N6A 5A5
GSK Investigational Site
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
GSK Investigational Site
Greenfield Park, Quebec, Canada, J4V 2H1
GSK Investigational Site
St-Jerome, Quebec, Canada, J7Z 5T3
Germany
GSK Investigational Site
Freiburg, Baden-Wuerttemberg, Germany, 79106
GSK Investigational Site
Friedrichshafen, Baden-Wuerttemberg, Germany, 88048
GSK Investigational Site
Ulm, Baden-Wuerttemberg, Germany, 89081
GSK Investigational Site
Erlangen, Bayern, Germany, 91054
GSK Investigational Site
Celle, Niedersachsen, Germany, 29223
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
GSK Investigational Site
Osnabrueck, Niedersachsen, Germany, 49076
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45122
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48149
GSK Investigational Site
Leipzig, Sachsen, Germany, 04103
GSK Investigational Site
Bremen, Germany, 28177
GSK Investigational Site
Hamburg, Germany, 22417
GSK Investigational Site
Hamburg, Germany, 22763
United Kingdom
GSK Investigational Site
Cambridge, United Kingdom, CB2 0QQ
GSK Investigational Site
Exeter, United Kingdom, EX2 5DW
GSK Investigational Site
Glasgow, United Kingdom, G51 4TF
GSK Investigational Site
Harrow, United Kingdom, HA1 3UJ
GSK Investigational Site
Liverpool, United Kingdom, L7 8XP
GSK Investigational Site
London, United Kingdom, SW17 0QT
GSK Investigational Site
London, United Kingdom, SE5 9RS
GSK Investigational Site
Newcastle upon Tyne, United Kingdom, NE1 4LP
GSK Investigational Site
Romford, United Kingdom, RM7 0AG
GSK Investigational Site
Salford, United Kingdom, M6 8HD
GSK Investigational Site
Torquay, United Kingdom, TQ2 7AA
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01808261     History of Changes
Other Study ID Numbers: 104615
Study First Received: February 14, 2013
Last Updated: August 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Ischemic Stroke

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

ClinicalTrials.gov processed this record on August 19, 2014