Last updated: 11/07/2018 00:28:07
Proof of Concept (POC) in patients with ischaemic stroke
EudraCT ID
EU CT Number
Not applicable
Trial status
Terminated (halted prematurely)
Terminated (halted prematurely)
Trial overview
Official title: Study MAG104615, a Proof of Concept Study for GSK249320 versus placebo in Stroke Patients
Trial description: Study MAG104615, a Proof of Concept Study for GSK249320 versus placebo in Stroke Patients.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Mean change from Baseline (BL) to month 3/ Day 90 in Gait velocity
Timeframe: BL (Day 1) and Month 3/Day 90
Secondary outcomes:
Mean change from BL to month 6/ Day 180 in Gait velocity
Timeframe: BL (Day 1) and Month 6/Day 180
Number of participants with indicated transition from one gait velocity category to another category at the indicated time points
Timeframe: BL (Day 1), Month 1/Day 30, Month 2/Day 60, Month 3/Day 90 and Month 6/Day 180.
Change from BL in dexterity as measured by Box and Blocks test
Timeframe: BL (Day 1), Month 1/Day 30, Month 2/Day 60, Month 3/Day 90 and Month 6/Day 180
Number of participants experiencing falls
Timeframe: BL (Day 1) Day 90 and Day 180
Number of falls over time
Timeframe: BL (Day 1), Day 90 and Day 180
Number of participants with serious adverse events (SAEs) and adverse events (AEs)
Timeframe: Up to 14 months
Number of participants with events common to stroke
Timeframe: From Day 1 until early withdrawal, death, Month 6/Day 180
Change from BL in vital signs- Systolic blood pressure (SBP) and Diastolic blood pressure (DBP)
Timeframe: BL (Day 1) , Day 6, Day 180 and early withdrawal (EW) visit
Change from BL in vitals signs-Heart rate
Timeframe: Day 1, Day 6, Day 180 and EW visit
Change from BL in ECG parameter-Heart rate
Timeframe: BL (Day 1) Day 6, Day 30 and EW visit
Change from BL in ECG parameters
Timeframe: BL (Day 1), Day 6, Day 30 and EW visit
Change from BL in clinical chemistry- Albumin and total protein
Timeframe: BL (Day 1), Day 6, Day 30, Day 90 and Day 180
Change from BL in clinical chemistry-urea/blood urea nitrogen (BUN), sodium (Na), potassium (K), glucose (Gluc), chloride (Cl), calcium (Ca)
Timeframe: BL (Day 1), Day 6, Day 30, Day 90 and Day 180
Change from BL in alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
Timeframe: BL (Day 1), Day 6, Day 30, Day 90 and Day 180
Change from BL in clinical chemistry- Direct Bilirubin, Total Bilirubin, Creatinine
Timeframe: BL (Day 1), Day 6, Day 30, Day 90 and Day 180
Change from BL in eosinophils (EOS), lymphocytes (LYM), total absolute neutrophil count (ANC), platelet (PLT) count, white blood cell (WBC) count
Timeframe: BL (Day 1), Day 6, Day 30, Day 90 and Day 180
Change from BL in hematology- Hemoglobin
Timeframe: BL (Day 1), Day 6, Day 30, Day 90 and Day 180
Change from baseline in hematology- Hematocrit
Timeframe: BL (Day 1), Day 6, Day 30, Day 90 and Day 180
Change from BL in NIHSS total score
Timeframe: BL (Day 1), Day 30, Day 90 and Day 180
Number of participants with suicidal ideation via Columbia Suicide Severity Rating Scale (CSSRS)
Timeframe: Da y 1, Da y 6, Day 30, Day 60, Day 90 and Day 180
Maximum observed plasma concentration (Cmax) for GSK249320
Timeframe: Pre-dose and post-dose up to Day 180
Time to reach maximum observed plasma concentration (Tmax) GSK249320
Timeframe: Pre-dose and post-dose up to Day 180
PK as measured by plasma decay half-life (t1/2) GSK249320
Timeframe: Up to Day 180
Area under the concentration-time curve from 0 to 5 days [AUC(0-5d)] and area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time [AUC(0-inf)] for GSK249320
Timeframe: Pre-dose and post-dose up to Day 180
Clearance (CL) for GSK249320
Timeframe: Up to Day 180
Volume of distribution (V1 and V2) and Volume at steady state (Vss) for GSK249320
Timeframe: Up to Day 180
Antibodies against GSK249320, assessed using Electrochemi-luminescent assay (ECL) assay
Timeframe: Day 1, Day 30, Day 180, EW visit and Follow-up visit
Interventions:
Drug: GSK249320 100/mg
Drug: Placebo
Enrollment:
134
Observational study model:
Not applicable
Primary completion date:
2014-28-07
Time perspective:
Not applicable
Clinical publications:
Steven C. Cramer, Lori A. Enney, Colleen K. Russell, Monica Simeoni, Thomas R. Thompson. Proof-of-Concept Randomized Trial of the Monoclonal Antibody GSK249320 Versus Placebo in Stroke Patients. Stroke . 2017;48(3):692-698.
Medical condition
Cerebrovascular Accident
Product
refanezumab
Collaborators
Not applicable
Study date(s)
May 2013 to July 2014
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 90 years
Accepts healthy volunteers
No
- 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].
- 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.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Freiburg, Baden-Wuerttemberg, Germany, 79106
Status
Study Complete
Location
GSK Investigational Site
Torquay, United Kingdom, TQ2 7AA
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Portland, Oregon, United States, 97239
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
Status
Study Complete
Location
GSK Investigational Site
Orange, California, United States, 92868-4280
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37232
Status
Study Complete
Location
GSK Investigational Site
Peoria, Illinois, United States, 61637
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Osnabrueck, Niedersachsen, Germany, 49076
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Newcastle upon Tyne, United Kingdom, NE1 4LP
Status
Study Complete
Location
GSK Investigational Site
Greenfield Park, Québec, Canada, J4V 2H1
Status
Study Complete
Location
GSK Investigational Site
Ulm, Baden-Wuerttemberg, Germany, 89081
Status
Study Complete
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45122
Status
Study Complete
Location
GSK Investigational Site
Liverpool, United Kingdom, L7 8XP
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Lexington, Kentucky, United States, 40536
Status
Study Complete
Location
GSK Investigational Site
Jacksonville, Florida, United States, 32209
Status
Study Complete
Location
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48149
Status
Study Complete
Location
GSK Investigational Site
Friedrichshafen, Baden-Wuerttemberg, Germany, 88048
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Terminated (halted prematurely)
Actual primary completion date
2014-28-07
Actual study completion date
2014-28-07
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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