Safety Escalating Repeat IV, in Stroke Patients

NCT ID: NCT00833989

Last Updated: 2017-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-08
• Study Completion Date: 2011-01-31

Brief Summary

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

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.

Conditions

Ischaemic Attack, Transient

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

PLACEBO

Group Type: PLACEBO_COMPARATOR

PLACEBO

Intervention Type: DRUG

Placebo

ACTIVE

Group Type: EXPERIMENTAL

GSK249320

Intervention Type: DRUG

I.V. infusion

Interventions

GSK249320

I.V. infusion

Intervention Type: DRUG

PLACEBO

Placebo

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Orange, California, United States

GSK Investigational Site

Fort Collins, Colorado, United States

GSK Investigational Site

Detroit, Michigan, United States

GSK Investigational Site

Portland, Oregon, United States

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Ulm, Baden-Wurttemberg, Germany

GSK Investigational Site

Wiesbaden, Hesse, Germany

GSK Investigational Site

Celle, Lower Saxony, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Cologne, North Rhine-Westphalia, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Mainz, Rhineland-Palatinate, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

Countries

United States; Canada; Germany

References

Cramer SC, Abila B, Scott NE, Simeoni M, Enney LA; MAG111539 Study Investigators. Safety, pharmacokinetics, and pharmacodynamics of escalating repeat doses of GSK249320 in patients with stroke. Stroke. 2013 May;44(5):1337-42. doi: 10.1161/STROKEAHA.111.674366. Epub 2013 Mar 7.

Reference Type: BACKGROUND

PMID: 23471268 (View on PubMed)

Study Documents

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol

View Document

Document Type: Individual Participant Data Set

View Document

Document Type: Dataset Specification

View Document

Document Type: Annotated Case Report Form

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Clinical Study Report

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

111539

Identifier Type: -

Identifier Source: org_study_id