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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01955707
Recruitment Status : Completed
First Posted : October 7, 2013
Results First Posted : July 1, 2016
Last Update Posted : July 1, 2016
Sponsor:
Information provided by (Responsible Party):
Biogen

Tracking Information
First Submitted Date  ICMJE September 30, 2013
First Posted Date  ICMJE October 7, 2013
Results First Submitted Date  ICMJE February 4, 2016
Results First Posted Date  ICMJE July 1, 2016
Last Update Posted Date July 1, 2016
Study Start Date  ICMJE January 2014
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 24, 2016)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 30, 2013)
Change in Infarct Volume From Baseline (Diffusion-Weighted Imaging [DWI]) to Day 5 (Fluid-Attenuated Inversion Recovery [FLAIR]) [ Time Frame: Day 5 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2016)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 30, 2013)
  • Change in Infarct Volume From Baseline (DWI) to Day 30 (FLAIR) [ Time Frame: Day 30 ]
  • Change in Infarct Volume From 24 hours (DWI) to Day 5 and Day 30 (FLAIR) [ Time Frame: Up to 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: Up to Day 90 ]
  • Modified Rankin Scale (mRS) distribution at Day 5, Day 30, and Day 90 [ Time Frame: Up to Day 90 ]
  • Barthel Index at Day 5, Day 30, and Day 90 [ Time Frame: Up to Day 90 ]
  • Number of subjects who experience Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Day 90 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Natalizumab on Infarct Volume in Acute Ischemic Stroke
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Acute Ischemic Stroke
Intervention  ICMJE
  • Drug: natalizumab
    Administered as described in the treatment arm
    Other Names:
    • Tysabri
    • BG00002
  • Drug: Placebo
    Matched placebo
Study Arms  ICMJE
  • Experimental: natalizumab
    300 mg single intravenous (IV) injection
    Intervention: Drug: natalizumab
  • Placebo Comparator: Placebo
    A single IV dose of placebo
    Intervention: Drug: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 5, 2015)
161
Original Estimated Enrollment  ICMJE
 (submitted: September 30, 2013)
200
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date February 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01955707
Other Study ID Numbers  ICMJE 101SK201
EUDRA CT NO: 2013-001514-15
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP