Back to resultsEffect of Natalizumab on Infarct Volume in Acute Ischemic Stroke (ACTION)
Primary Purpose
Acute Ischemic Stroke
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
natalizumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Acute Ischemic Stroke
Eligibility Criteria
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.
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
natalizumab
Placebo
Arm Description
300 mg single intravenous (IV) injection
A single IV dose of placebo
Outcomes
Primary Outcome Measures
Change in Infarct Volume From Baseline (Diffusion-Weighted Imaging [DWI]) to Day 5 (Fluid-Attenuated Inversion Recovery [FLAIR])
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.
Secondary Outcome Measures
Change in Infarct Volume From Baseline (DWI) to 24 Hours (FLAIR)
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.
Change in Infarct Volume From Baseline (DWI) to Day 30 (FLAIR)
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.
Change in Infarct Volume From 24 Hours (FLAIR) to Day 5 (FLAIR)
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.
Change in Infarct Volume From 24 Hours (FLAIR) to Day 30 (FLAIR)
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.
Change in Infarct Volume From Day 5 (FLAIR) to Day 30 (FLAIR)
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.
Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and 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.
Modified Rankin Scale (mRS) Distribution at 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.
Barthel Index at 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.
Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01955707
Brief Title
Effect of Natalizumab on Infarct Volume in Acute Ischemic Stroke
Acronym
ACTION
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
January 2014 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
April 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Ischemic Stroke
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
161 (Actual)
8. Arms, Groups, and Interventions
Arm Title
natalizumab
Arm Type
Experimental
Arm Description
300 mg single intravenous (IV) injection
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
A single IV dose of placebo
Intervention Type
Drug
Intervention Name(s)
natalizumab
Other Intervention Name(s)
Tysabri, BG00002
Intervention Description
Administered as described in the treatment arm
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matched placebo
Primary Outcome Measure Information:
Title
Change in Infarct Volume From Baseline (Diffusion-Weighted Imaging [DWI]) to Day 5 (Fluid-Attenuated Inversion Recovery [FLAIR])
Description
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.
Time Frame
Baseline, Day 5
Secondary Outcome Measure Information:
Title
Change in Infarct Volume From Baseline (DWI) to 24 Hours (FLAIR)
Description
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.
Time Frame
Baseline, 24 hrs
Title
Change in Infarct Volume From Baseline (DWI) to Day 30 (FLAIR)
Description
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.
Time Frame
Baseline, Day 30
Title
Change in Infarct Volume From 24 Hours (FLAIR) to Day 5 (FLAIR)
Description
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.
Time Frame
24 hours, Day 5
Title
Change in Infarct Volume From 24 Hours (FLAIR) to Day 30 (FLAIR)
Description
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.
Time Frame
24 hours, Day 30
Title
Change in Infarct Volume From Day 5 (FLAIR) to Day 30 (FLAIR)
Description
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.
Time Frame
Day 5, Day 30
Title
Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90
Description
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.
Time Frame
Baseline, 24 hours, Day 5, Day 30, Day 90
Title
Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90
Description
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.
Time Frame
Day 5, Day 30, and Day 90
Title
Barthel Index at Day 5, Day 30, and Day 90
Description
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.
Time Frame
Day 5, Day 30, and Day 90
Title
Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
Up to Day 90 ± 5 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
San Diego
State/Province
California
Country
United States
Facility Name
Research Site
City
Gainesville
State/Province
Florida
Country
United States
Facility Name
Research Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Research Site
City
Golden Valley
State/Province
Minnesota
ZIP/Postal Code
55422
Country
United States
Facility Name
Research Site
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Research Site
City
Lake Success
State/Province
New York
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Research Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Research Site
City
Akron
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45409
Country
United States
Facility Name
Research Site
City
Toledo
State/Province
Ohio
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
Country
United States
Facility Name
Research Site
City
Tualatin
State/Province
Oregon
ZIP/Postal Code
97062
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
Research Site
City
Dallas
State/Province
Texas
Country
United States
Facility Name
Research Site
City
Charlottesville
State/Province
Virginia
Country
United States
Facility Name
Research Site
City
Milwaukee
State/Province
Wisconsin
Country
United States
Facility Name
Research Site
City
Altenburg
ZIP/Postal Code
04600
Country
Germany
Facility Name
Research Site
City
Bad Neustadt
ZIP/Postal Code
97616
Country
Germany
Facility Name
Research Site
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Facility Name
Research Site
City
Bonn
Country
Germany
Facility Name
Research Site
City
Duesseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Research Site
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Research Site
City
Frankfurt
ZIP/Postal Code
60528
Country
Germany
Facility Name
Research Site
City
Hannover
Country
Germany
Facility Name
Research Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Research Site
City
Idar-Oberstein
ZIP/Postal Code
55743
Country
Germany
Facility Name
Research Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Research Site
City
Ludwigshafen
ZIP/Postal Code
67063
Country
Germany
Facility Name
Research Site
City
Ludwigshafen
Country
Germany
Facility Name
Research Site
City
Mannheim
Country
Germany
Facility Name
Research Site
City
Trier
ZIP/Postal Code
54290
Country
Germany
Facility Name
Research Site
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Research Site
City
Ulm
Country
Germany
Facility Name
Research Site
City
Albacete
ZIP/Postal Code
02006
Country
Spain
Facility Name
Research Site
City
Badalona
ZIP/Postal Code
8916
Country
Spain
Facility Name
Research Site
City
Barakaldo
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
8003
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
8035
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
8036
Country
Spain
Facility Name
Research Site
City
Girona
ZIP/Postal Code
17007
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Research Site
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Research Site
City
Santiago de Compostela
ZIP/Postal Code
15706
Country
Spain
Facility Name
Research Site
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
Research Site
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Research Site
City
Valencia
Country
Spain
Facility Name
Research Site
City
Valladolid
ZIP/Postal Code
47005
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
28229893
Citation
Elkins J, Veltkamp R, Montaner J, Johnston SC, Singhal AB, Becker K, Lansberg MG, Tang W, Chang I, Muralidharan K, Gheuens S, Mehta L, Elkind MSV. Safety and efficacy of natalizumab in patients with acute ischaemic stroke (ACTION): a randomised, placebo-controlled, double-blind phase 2 trial. Lancet Neurol. 2017 Mar;16(3):217-226. doi: 10.1016/S1474-4422(16)30357-X. Epub 2017 Feb 15.
Results Reference
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Effect of Natalizumab on Infarct Volume in Acute Ischemic Stroke
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