Effect of Natalizumab on Infarct Volume in Acute Ischemic Stroke (ACTION)

May 24, 2016 updated by: Biogen

A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Parallel-Group Study to Evaluate the Safety and Efficacy of Intravenous Natalizumab (BG00002) on Reducing Infarct Volume in Acute Ischemic Stroke

The primary objective of the study is to determine whether one 300 mg dose of intravenous (IV) natalizumab reduces change in infarct volume from Baseline to Day 5 on magnetic resonance imaging (MRI) in participants with acute ischemic stroke when given at ≤6 hours or at >6 to ≤9 hours from when they were last known normal (LKN).

The secondary objectives of this study in this study population are as follows: to assess the efficacy of natalizumab on change in infarct volume from Baseline to Day 30; to assess efficacy of natalizumab on change in infarct volume from 24 hours to Day 5 and Day 30; to assess the efficacy of natalizumab on clinical measures of stroke outcome; to assess the safety of natalizumab in participants with acute ischemic stroke.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

161

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Altenburg, Germany, 04600
        • Research Site
      • Bad Neustadt, Germany, 97616
        • Research Site
      • Berlin, Germany, 12203
        • Research Site
      • Bonn, Germany
        • Research Site
      • Duesseldorf, Germany, 40225
        • Research Site
      • Erlangen, Germany, 91054
        • Research Site
      • Frankfurt, Germany, 60528
        • Research Site
      • Hannover, Germany
        • Research Site
      • Heidelberg, Germany, 69120
        • Research Site
      • Idar-Oberstein, Germany, 55743
        • Research Site
      • Leipzig, Germany, 04103
        • Research Site
      • Ludwigshafen, Germany
        • Research Site
      • Ludwigshafen, Germany, 67063
        • Research Site
      • Mannheim, Germany
        • Research Site
      • Trier, Germany, 54290
        • Research Site
      • Tübingen, Germany, 72076
        • Research Site
      • Ulm, Germany
        • Research Site
  • Spain
      • Albacete, Spain, 02006
        • Research Site
      • Badalona, Spain, 8916
        • Research Site
      • Barakaldo, Spain
        • Research Site
      • Barcelona, Spain, 8035
        • Research Site
      • Barcelona, Spain, 8036
        • Research Site
      • Barcelona, Spain, 8003
        • Research Site
      • Girona, Spain, 17007
        • Research Site
      • Madrid, Spain, 28034
        • Research Site
      • Pamplona, Spain, 31008
        • Research Site
      • Santiago de Compostela, Spain, 15706
        • Research Site
      • Sevilla, Spain, 41009
        • Research Site
      • Sevilla, Spain, 41013
        • Research Site
      • Valencia, Spain
        • Research Site
      • Valladolid, Spain, 47005
        • Research Site
  • United States
    • California
      • San Diego, California, United States
        • Research Site
    • Florida
      • Gainesville, Florida, United States
        • Research Site
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Research Site
    • Minnesota
      • Golden Valley, Minnesota, United States, 55422
        • Research Site
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Research Site
    • New York
      • Lake Success, New York, United States
        • Research Site
      • New York, New York, United States, 10032
        • Research Site
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Research Site
    • Ohio
      • Akron, Ohio, United States
        • Research Site
      • Dayton, Ohio, United States, 45409
        • Research Site
      • Toledo, Ohio, United States
        • Research Site
    • Oregon
      • Portland, Oregon, United States
        • Research Site
      • Tualatin, Oregon, United States, 97062
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Research Site
    • Tennessee
      • Nashville, Tennessee, United States
        • Research Site
    • Texas
      • Dallas, Texas, United States
        • Research Site
    • Virginia
      • Charlottesville, Virginia, United States
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, United States
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • Diagnosis of acute ischemic stroke.
  • Score of ≥6 points on the National Institute of Health Stroke Scale (NIHSS) at Screening.
  • At least 1 acute infarct with largest diameter of more than 2 cm on Baseline brain diffusion-weighted imaging (DWI).
  • Participants who have received reperfusion therapy may be eligible to participate but must meet all eligibility criteria and perform the Baseline study magnetic resonance imaging (MRI) after reperfusion therapy has been completed.
  • Subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for at least 3 months after their dose of study treatment.

Key Exclusion Criteria:

  • Presence of any intracranial hemorrhage (ICH) on head computed tomography (CT) or non-petechial ICH on screening MRI.
  • Stroke isolated to the brainstem.
  • Presence of coma
  • Expected to die OR unable to be evaluated within 5 days.
  • Hypotension requiring the use of intravenous (IV) vasopressor support or systolic blood pressure <90 mmHg at the time of randomization.
  • Known prior treatment with natalizumab.
  • Immunocompromised subjects, as determined by the Investigator.
  • History of progressive multifocal leukoencephalopathy (PML).
  • Contraindications to MRI, e.g., implanted pacemaker or other contraindicated implanted metal devices, history of or risk for side effects from gadolinium, or claustrophobia that cannot be medically managed.

NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: natalizumab
300 mg single intravenous (IV) injection
Drug: natalizumab
Administered as described in the treatment arm
Other Names:
  • Tysabri
  • BG00002
Placebo Comparator: Placebo
A single IV dose of placebo
Drug: Placebo
Matched placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Infarct Volume From Baseline (Diffusion-Weighted Imaging [DWI]) to Day 5 (Fluid-Attenuated Inversion Recovery [FLAIR])
Time Frame: Baseline, Day 5
Relative growth of infarct volume from Baseline (relative growth = FLAIR at Day 5 divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth.
Baseline, Day 5

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Infarct Volume From Baseline (DWI) to 24 Hours (FLAIR)
Time Frame: Baseline, 24 hrs
Relative growth of infarct volume from Baseline (relative growth = FLAIR at 24 hours divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth.
Baseline, 24 hrs
Change in Infarct Volume From Baseline (DWI) to Day 30 (FLAIR)
Time Frame: Baseline, Day 30
Relative growth of infarct volume from Baseline (relative growth = FLAIR at Day 30 divided by Baseline DWI). Geometric mean calculated as the exponential of the mean log relative growth.
Baseline, Day 30
Change in Infarct Volume From 24 Hours (FLAIR) to Day 5 (FLAIR)
Time Frame: 24 hours, Day 5
Relative growth of infarct volume from 24 hours (relative growth = FLAIR at Day 5 divided by FLAIR at 24 hours). Geometric mean calculated as the exponential of the mean log relative growth.
24 hours, Day 5
Change in Infarct Volume From 24 Hours (FLAIR) to Day 30 (FLAIR)
Time Frame: 24 hours, Day 30
Relative growth in infarct volume from Baseline (relative growth = FLAIR Day 30 divided by FLAIR at 24 hours ). Geometric mean calculated as the exponential of the mean log relative growth.
24 hours, Day 30
Change in Infarct Volume From Day 5 (FLAIR) to Day 30 (FLAIR)
Time Frame: Day 5, Day 30
Relative growth of infarct volume from Day 5 (relative growth = FLAIR at Day 30 divided by FLAIR at Day 5). Geometric mean calculated as the exponential of the mean log relative growth.
Day 5, Day 30
Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90
Time Frame: Baseline, 24 hours, Day 5, Day 30, Day 90
The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Scores for the NIHSS range from 0 to 42, with 0 representing no symptoms and 42 representing death.
Baseline, 24 hours, Day 5, Day 30, Day 90
Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90
Time Frame: Day 5, Day 30, and Day 90
The mRS measures independence, rather than neurologic function, with specific tasks pre- and post-stroke, respectively. The scale consists of 7 grades, from 0 to 6, with 0 corresponding to no symptoms and 6 corresponding to death. The distribution of mRS scores was summarized at each timepoint. An excellent outcome on the mRS was defined as a score of 0 or 1, while a good outcome was defined as a score of 0, 1, or 2.
Day 5, Day 30, and Day 90
Barthel Index at Day 5, Day 30, and Day 90
Time Frame: Day 5, Day 30, and Day 90
The Barthel Index consists of 10 items that measure a person's daily functioning, specifically the activities of daily living and mobility, and can be used to determine a baseline level of functioning and to monitor change in activities of daily living over time. The scores for each of the items are summed to create a total score up to a potential of 100, with higher scores representing a greater level of independence.
Day 5, Day 30, and Day 90
Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to Day 90 ± 5 days
AE: any untoward medical occurrence that does not necessarily have a causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose: results in death; in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. Events were categorized as severe, moderate, or mild, and related or not related to study treatment.
Up to Day 90 ± 5 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biogen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2014

Primary Completion (Actual)

February 1, 2015

Study Completion (Actual)

April 1, 2015

Study Registration Dates

First Submitted

September 30, 2013

First Submitted That Met QC Criteria

September 30, 2013

First Posted (Estimate)

October 7, 2013

Study Record Updates

Last Update Posted (Estimate)

July 1, 2016

Last Update Submitted That Met QC Criteria

May 24, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 101SK201
  • EUDRA CT NO: 2013-001514-15

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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