Back to resultsSafety and Efficacy of Intravenous Natalizumab in Acute Ischemic Stroke (ACTION2)
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 focused on measuring Stroke
Eligibility Criteria
Key Inclusion Criteria:
- Clinical diagnosis of supratentorial acute ischemic stroke defined by LKN ≤24 hours prior to study treatment initiation.
- Score of 5 to 23 points, inclusive, on the NIHSS at Screening for subjects initiating treatment ≤9 hours from LKN. Note: NIHSS eligibility must be confirmed within 60 minutes prior to randomization.
- Score of 5 to 15 points, inclusive, on the NIHSS at Screening for subjects initiating treatment >9 to ≤24 hours from LKN. Note: NIHSS eligibility must be confirmed within 60 minutes prior to randomization.
- Prior to index stroke, patient was able to perform basic activities of daily living without assistance: dressing, eating, walking, bathing, and using the toilet.
- For those subjects who underwent a cranial MRI, there is at least 1 acute infarct with a diameter of ≥2 cm on baseline brain diffusion-weighted imaging.
Key Exclusion Criteria:
- Lacunar or isolated brainstem or cerebellar stroke based on clinical assessment and available acute imaging studies performed under the standard of care.
- Presence of acute intracranial hemorrhage on acute brain CT or MRI. However, petechial hemorrhages of ≤1 cm are not exclusionary.
- Severe stroke defined by imaging criteria based on either one of the following:
- Alberta Stroke Program Early CT (ASPECT) score of 0 to 4 based on head CT or
- Acute infarct volume on MRI diffusion weighed imaging greater than or equal to 70 mL
- Seizure at the onset of stroke.
- Known history of prior treatment with natalizumab.
- Known history of active viral hepatitis B or C.
- Signs and symptoms of active or acute infection.
NOTE: Other protocol-defined inclusion/exclusion criteria may apply.
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
natalizumab high dose
natalizumab low dose
Placebo
Arm Description
Single IV (intravenous) dose natalizumab at baseline at one of two treatment windows, either within 9 hours of last known normal (LKN) or between 9-24 hours after LKN.
Single IV (intravenous) dose natalizumab at baseline at one of two treatment windows, either within 9 hours of last known normal (LKN) or between 9-24 hours after LKN.
Single dose of Placebo IV at baseline at one of two treatment windows, either within 9 hours of last known normal (LKN) or between 9-24 hours after LKN.
Outcomes
Primary Outcome Measures
Percentage of Participants With Composite Global Measure of Functional Disability Excellent Outcome at Day 90
The composite global measure of functional disability excellent outcome was based on a score of 0 or 1 on the modified Rankin Scale (mRS) and a score of >=95 on the Barthel Index (BI). mRS measures independence, rather than neurological function, with specific tasks pre- and post-stroke. The scale consists of 7 grades, from 0 to 6, with 0 corresponding to no symptoms and 6 corresponding to death. BI consists of 10 items that measure a participant's daily functioning, specifically the activities of daily living and mobility. The items include feeding, moving from wheelchair to bed and returning, grooming, transferring to and from a toilet, bathing, walking on a level surface, going up and down stairs, dressing, and maintaining continence of bowels and bladder. The scores for each of the items are summed to create a total score of 0 to 100. The higher the score, the more "independent" the participant is.
Secondary Outcome Measures
Percentage of Participants With Excellent Outcome in mRS Score at Day 90
Excellent mRS is defined as mRS score of 0 or 1. mRS measures independence, rather than neurological function, with specific tasks pre- and poststroke. The scale consists of 7 grades, from 0 to 6, with 0 corresponding to no symptoms and 6 corresponding to death.
Percentage of Participants With Excellent Outcome in BI Score at Day 90
Excellent BI outcome is defined as a score of >=95. BI consists of 10 items that measure a participant's daily functioning, specifically the activities of daily living and mobility. The items include feeding, moving from wheelchair to bed and returning, grooming, transferring to and from a toilet, bathing, walking on a level surface, going up and down stairs, dressing, and maintaining continence of bowels and bladder. The scores for each of the items are summed to create a total score of 0 to 100. The higher the score, the more "independent" the participant is.
Stroke Impact Scale-16 (SIS-16) Score Using a Repeated Measures Mixed Effects Model at Day 90
The SIS-16 is a 16-item physical dimension instrument that was developed as a brief, stand-alone tool for measuring the physical aspects of stroke recovery. The 16 physical aspects are rated on a 1 to 5 scale as follows: not difficult at all (5), a little difficult (4), somewhat difficult (3), very difficult (2), and could not do at all (1). Total score range is 16 to 80, with higher scores indicating higher levels of health-related quality of life and function.
Montreal Cognitive Assessment (MoCA) Score at Day 90
The MoCA is a global cognitive screening test with favorable psychometric properties It screens 8 domains: visuospatial/executive, naming, memory, attention, language, abstraction, delayed recall, and orientation. Time to administer the MoCA is approximately 10 minutes. The total possible score is 0 to 30 points; a score of 26 or above is considered normal, <10 (severe cognitive impairment), 10-17 (moderate cognitive impairment) and >=18 (mild cognitive impairment).
Change From Baseline in National Institute of Health Stroke Scale (NIHSS) Score at Day 90
The NIHSS is a reliable tool for rapidly evaluating the effects of acute cerebral infarction. A trained observer rates the participant's ability to answer questions and perform activities relating to level of consciousness, language, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, sensory loss, and extinction and inattention (formerly neglect). There are 15 items. Total score ranges from 0 as normal to a maximum possible total severity score of 42 for all items. Higher the score, more the severity. A negative change from Baseline indicates improvement.
Number of Participants Experiencing Adverse Events (AE)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Number of Participants Experiencing Serious Adverse Events (SAE)
A SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization, results in a significant disability/incapacity or congenital anomaly.
Percentage of Participants With Dose Response at Day 90
Percentage of participants with dose response was evaluated in proportion of excellent outcome on mRS and BI.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02730455
Brief Title
Safety and Efficacy of Intravenous Natalizumab in Acute Ischemic Stroke
Acronym
ACTION2
Official Title
Multicenter, Double-Blind, Placebo-Controlled, Randomized, Parallel-Group, Dose-Ranging Study to Evaluate the Safety and Efficacy of Intravenous Natalizumab (BG00002) in Acute Ischemic Stroke
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
July 18, 2016 (Actual)
Primary Completion Date
November 20, 2017 (Actual)
Study Completion Date
November 20, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of the study is to assess the clinical effects of natalizumab versus placebo in acute ischemic stroke on clinical measures of functional independence and activities of daily living. The secondary objective of the study is to explore dose and exposure response and the clinical treatment effects of natalizumab versus placebo in acute ischemic stroke on the following: measures of independence, activities of daily living, neurologic function, quality of life, cognition, and safety and tolerability
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Ischemic Stroke
Keywords
Stroke
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
277 (Actual)
8. Arms, Groups, and Interventions
Arm Title
natalizumab high dose
Arm Type
Experimental
Arm Description
Single IV (intravenous) dose natalizumab at baseline at one of two treatment windows, either within 9 hours of last known normal (LKN) or between 9-24 hours after LKN.
Arm Title
natalizumab low dose
Arm Type
Experimental
Arm Description
Single IV (intravenous) dose natalizumab at baseline at one of two treatment windows, either within 9 hours of last known normal (LKN) or between 9-24 hours after LKN.
Arm Title
Placebo
Arm Type
Experimental
Arm Description
Single dose of Placebo IV at baseline at one of two treatment windows, either within 9 hours of last known normal (LKN) or between 9-24 hours after LKN.
Intervention Type
Drug
Intervention Name(s)
natalizumab
Other Intervention Name(s)
BG00002
Intervention Description
Administered as specified in the treatment arm
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matched placebo
Primary Outcome Measure Information:
Title
Percentage of Participants With Composite Global Measure of Functional Disability Excellent Outcome at Day 90
Description
The composite global measure of functional disability excellent outcome was based on a score of 0 or 1 on the modified Rankin Scale (mRS) and a score of >=95 on the Barthel Index (BI). mRS measures independence, rather than neurological function, with specific tasks pre- and post-stroke. The scale consists of 7 grades, from 0 to 6, with 0 corresponding to no symptoms and 6 corresponding to death. BI consists of 10 items that measure a participant's daily functioning, specifically the activities of daily living and mobility. The items include feeding, moving from wheelchair to bed and returning, grooming, transferring to and from a toilet, bathing, walking on a level surface, going up and down stairs, dressing, and maintaining continence of bowels and bladder. The scores for each of the items are summed to create a total score of 0 to 100. The higher the score, the more "independent" the participant is.
Time Frame
Day 90
Secondary Outcome Measure Information:
Title
Percentage of Participants With Excellent Outcome in mRS Score at Day 90
Description
Excellent mRS is defined as mRS score of 0 or 1. mRS measures independence, rather than neurological function, with specific tasks pre- and poststroke. The scale consists of 7 grades, from 0 to 6, with 0 corresponding to no symptoms and 6 corresponding to death.
Time Frame
Day 90
Title
Percentage of Participants With Excellent Outcome in BI Score at Day 90
Description
Excellent BI outcome is defined as a score of >=95. BI consists of 10 items that measure a participant's daily functioning, specifically the activities of daily living and mobility. The items include feeding, moving from wheelchair to bed and returning, grooming, transferring to and from a toilet, bathing, walking on a level surface, going up and down stairs, dressing, and maintaining continence of bowels and bladder. The scores for each of the items are summed to create a total score of 0 to 100. The higher the score, the more "independent" the participant is.
Time Frame
Day 90
Title
Stroke Impact Scale-16 (SIS-16) Score Using a Repeated Measures Mixed Effects Model at Day 90
Description
The SIS-16 is a 16-item physical dimension instrument that was developed as a brief, stand-alone tool for measuring the physical aspects of stroke recovery. The 16 physical aspects are rated on a 1 to 5 scale as follows: not difficult at all (5), a little difficult (4), somewhat difficult (3), very difficult (2), and could not do at all (1). Total score range is 16 to 80, with higher scores indicating higher levels of health-related quality of life and function.
Time Frame
Day 90
Title
Montreal Cognitive Assessment (MoCA) Score at Day 90
Description
The MoCA is a global cognitive screening test with favorable psychometric properties It screens 8 domains: visuospatial/executive, naming, memory, attention, language, abstraction, delayed recall, and orientation. Time to administer the MoCA is approximately 10 minutes. The total possible score is 0 to 30 points; a score of 26 or above is considered normal, <10 (severe cognitive impairment), 10-17 (moderate cognitive impairment) and >=18 (mild cognitive impairment).
Time Frame
Day 90
Title
Change From Baseline in National Institute of Health Stroke Scale (NIHSS) Score at Day 90
Description
The NIHSS is a reliable tool for rapidly evaluating the effects of acute cerebral infarction. A trained observer rates the participant's ability to answer questions and perform activities relating to level of consciousness, language, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, sensory loss, and extinction and inattention (formerly neglect). There are 15 items. Total score ranges from 0 as normal to a maximum possible total severity score of 42 for all items. Higher the score, more the severity. A negative change from Baseline indicates improvement.
Time Frame
Baseline, Day 90
Title
Number of Participants Experiencing Adverse Events (AE)
Description
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time Frame
Baseline up to Day 90
Title
Number of Participants Experiencing Serious Adverse Events (SAE)
Description
A SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization, results in a significant disability/incapacity or congenital anomaly.
Time Frame
Baseline up to Day 90
Title
Percentage of Participants With Dose Response at Day 90
Description
Percentage of participants with dose response was evaluated in proportion of excellent outcome on mRS and BI.
Time Frame
Day 90
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Clinical diagnosis of supratentorial acute ischemic stroke defined by LKN ≤24 hours prior to study treatment initiation.
Score of 5 to 23 points, inclusive, on the NIHSS at Screening for subjects initiating treatment ≤9 hours from LKN. Note: NIHSS eligibility must be confirmed within 60 minutes prior to randomization.
Score of 5 to 15 points, inclusive, on the NIHSS at Screening for subjects initiating treatment >9 to ≤24 hours from LKN. Note: NIHSS eligibility must be confirmed within 60 minutes prior to randomization.
Prior to index stroke, patient was able to perform basic activities of daily living without assistance: dressing, eating, walking, bathing, and using the toilet.
For those subjects who underwent a cranial MRI, there is at least 1 acute infarct with a diameter of ≥2 cm on baseline brain diffusion-weighted imaging.
Key Exclusion Criteria:
Lacunar or isolated brainstem or cerebellar stroke based on clinical assessment and available acute imaging studies performed under the standard of care.
Presence of acute intracranial hemorrhage on acute brain CT or MRI. However, petechial hemorrhages of ≤1 cm are not exclusionary.
Severe stroke defined by imaging criteria based on either one of the following:
Alberta Stroke Program Early CT (ASPECT) score of 0 to 4 based on head CT or
Acute infarct volume on MRI diffusion weighed imaging greater than or equal to 70 mL
Seizure at the onset of stroke.
Known history of prior treatment with natalizumab.
Known history of active viral hepatitis B or C.
Signs and symptoms of active or acute infection.
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
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Facility Name
Research Site
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
Research Site
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Research Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Research Site
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
Facility Name
Research Site
City
Fort Wayne
State/Province
Indiana
ZIP/Postal Code
46845
Country
United States
Facility Name
Research Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Research Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
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
19104
Country
United States
Facility Name
Research Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97201
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97225
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Research Site
City
Abington
State/Province
Pennsylvania
ZIP/Postal Code
19001
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Research Site
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Research Site
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920-6999
Country
United States
Facility Name
Research Site
City
Altenburg
ZIP/Postal Code
04600
Country
Germany
Facility Name
Research Site
City
Bad Neustadt/Saale
ZIP/Postal Code
97616
Country
Germany
Facility Name
Research Site
City
Bamberg
ZIP/Postal Code
96049
Country
Germany
Facility Name
Research Site
City
Bergisch Gladbach
ZIP/Postal Code
51465
Country
Germany
Facility Name
Research Site
City
Dresden
ZIP/Postal Code
01067
Country
Germany
Facility Name
Research Site
City
Dresden
ZIP/Postal Code
01307
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
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Research Site
City
Heidelberg
ZIP/Postal Code
69120
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
Mannheim
ZIP/Postal Code
68167
Country
Germany
Facility Name
Research Site
City
Minden
ZIP/Postal Code
32429
Country
Germany
Facility Name
Research Site
City
Muenster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Research Site
City
Trier
ZIP/Postal Code
54292
Country
Germany
Facility Name
Research Site
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Research Site
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Research Site
City
Albacete
ZIP/Postal Code
02008
Country
Spain
Facility Name
Research Site
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Research Site
City
Girona
ZIP/Postal Code
17007
Country
Spain
Facility Name
Research Site
City
Lugo
ZIP/Postal Code
27003
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Research Site
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Research Site
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Research Site
City
Sevilla
ZIP/Postal Code
41017
Country
Spain
Facility Name
Research Site
City
Valladolid
ZIP/Postal Code
47005
Country
Spain
Facility Name
Research Site
City
London
State/Province
Greater London
ZIP/Postal Code
SW17 0QT
Country
United Kingdom
Facility Name
Research Site
City
London
State/Province
Greater London
ZIP/Postal Code
W6 8RF
Country
United Kingdom
Facility Name
Research Site
City
Harrow
State/Province
Middlesex
ZIP/Postal Code
HA1 3UJ
Country
United Kingdom
Facility Name
Research Site
City
Stoke on Trent
State/Province
Staffordshire
ZIP/Postal Code
ST4 6QG
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
32591475
Citation
Elkind MSV, Veltkamp R, Montaner J, Johnston SC, Singhal AB, Becker K, Lansberg MG, Tang W, Kasliwal R, Elkins J. Natalizumab in acute ischemic stroke (ACTION II): A randomized, placebo-controlled trial. Neurology. 2020 Aug 25;95(8):e1091-e1104. doi: 10.1212/WNL.0000000000010038. Epub 2020 Jun 26.
Results Reference
derived
Learn more about this trial
Safety and Efficacy of Intravenous Natalizumab in Acute Ischemic Stroke
We'll reach out to this number within 24 hrs