Proof of Concept (POC) in Patients With Ischaemic Stroke

NCT01808261 | Terminated Phase 2 Results DMC

• 1 other identifier: 104615
• Study Type: interventional
• Target: 134
• Locations: 4 countries
• Sites: 36

Brief Summary

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

Conditions

Cerebrovascular Accident

Keywords

Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline (BL) to Month 3/ Day 90 in Gait Velocity

  Gait is the way or manner in which a person walks. Gait velocity (walking speed) is an objective, quantitative measure of lower extremity motor recovery in individuals who have had a stroke. Participants were asked to walk at their usual pace over a level, indoor 10 meter (m) distance and were allowed to use their normal assistive devices. The time (seconds\[s\]) taken by the participants to travel the 10 m distance was recorded. Gait velocity (m/s) as assessed by study personnel was derived as: 10 divided by time to walk 10 m. Two trials of gait velocity were conducted at each time point. Change from BL was calculated as the mean Month 3/Day 90 value minus the mean BL value. BL was defined as Day 1. The measure type displayed are posterior means.

  BL (Day 1) and Month 3/Day 90

Secondary Outcomes (27)

• Mean Change From BL to Month 6/ Day 180 in Gait Velocity

  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

  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

  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

  BL (Day 1) Day 90 and Day 180

• Number of Falls Over Time

  BL (Day 1), Day 90 and Day 180

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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). Placebo is for intravenous (IV) use only.

Drug: Placebo

GSK249320 100/mg

ACTIVE COMPARATOR

Clear to opalescent, colorless to pale yellow or pale brown, and is supplied as a sterile, concentrated solution (1000mg/vial). GSK249320 is for IV use only.

Drug: GSK249320 100/mg

Interventions

GSK249320 100/mg DRUG

Clear to opalescent, colorless to pale yellow or pale brown, and is supplied as a sterile, concentrated solution (1000mg/vial). GSK249320 is for IV use only.

GSK249320 100/mg

Placebo DRUG

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). Placebo is for intravenous (IV) use only.

Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (36)

GSK Investigational Site

Orange, California, 92868-4280, United States

Location

GSK Investigational Site

Jacksonville, Florida, 32209, United States

Location

GSK Investigational Site

Peoria, Illinois, 61637, United States

Location

GSK Investigational Site

Lexington, Kentucky, 40536, United States

Location

GSK Investigational Site

Portland, Oregon, 97239, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37232, United States

Location

GSK Investigational Site

Edmonton, Alberta, T6G 2B7, Canada

Location

GSK Investigational Site

Edmonton, Alberta, T6L 5X8, Canada

Location

GSK Investigational Site

London, Ontario, N6A 5A5, Canada

Location

GSK Investigational Site

Toronto, Ontario, M4N 3M5, Canada

Location

GSK Investigational Site

Greenfield Park, Quebec, J4V 2H1, Canada

Location

GSK Investigational Site

Saint-Jérôme, Quebec, J7Z 5T3, Canada

Location

GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

GSK Investigational Site

Friedrichshafen, Baden-Wurttemberg, 88048, Germany

Location

GSK Investigational Site

Ulm, Baden-Wurttemberg, 89081, Germany

Location

GSK Investigational Site

Erlangen, Bavaria, 91054, Germany

Location

GSK Investigational Site

Celle, Lower Saxony, 29223, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Osnabrück, Lower Saxony, 49076, Germany

Location

GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

Location

GSK Investigational Site

Münster, North Rhine-Westphalia, 48149, Germany

Location

GSK Investigational Site

Leipzig, Saxony, 04103, Germany

Location

GSK Investigational Site

Bremen, 28177, Germany

Location

GSK Investigational Site

Hamburg, 22417, Germany

Location

GSK Investigational Site

Hamburg, 22763, Germany

Location

GSK Investigational Site

Cambridge, CB2 0QQ, United Kingdom

Location

GSK Investigational Site

Exeter, EX2 5DW, United Kingdom

Location

GSK Investigational Site

Glasgow, G51 4TF, United Kingdom

Location

GSK Investigational Site

Harrow, HA1 3UJ, United Kingdom

Location

GSK Investigational Site

Liverpool, L7 8XP, United Kingdom

Location

GSK Investigational Site

London, SE5 9RS, United Kingdom

Location

GSK Investigational Site

London, SW17 0QT, United Kingdom

Location

GSK Investigational Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

GSK Investigational Site

Romford, RM7 0AG, United Kingdom

Location

GSK Investigational Site

Salford, M6 8HD, United Kingdom

Location

GSK Investigational Site

Torquay, TQ2 7AA, United Kingdom

Location

Related Publications (1)

• Cramer SC, Enney LA, Russell CK, Simeoni M, Thompson TR. Proof-of-Concept Randomized Trial of the Monoclonal Antibody GSK249320 Versus Placebo in Stroke Patients. Stroke. 2017 Mar;48(3):692-698. doi: 10.1161/STROKEAHA.116.014517. Epub 2017 Feb 22.

  PMID: 28228578 DERIVED

Related Links

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

MeSH Terms

Conditions

Stroke; Ischemic Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Limitations and Caveats

The study was terminated early, on 27 May 2014, at the planned interim analysis for futility.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2013
• First Posted: March 11, 2013
• Study Start: May 18, 2013
• Primary Completion: July 28, 2014
• Study Completion: July 28, 2014
• Last Updated: November 17, 2017
• Results First Posted: October 3, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will share

Locations

US (6); GB (11); DE (13); CA (6)