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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT01955707
First received: September 30, 2013
Last updated: May 24, 2016
Last verified: May 2016
  Purpose

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.


Condition Intervention Phase
Acute Ischemic Stroke
Drug: natalizumab
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • Change in Infarct Volume From Baseline (Diffusion-Weighted Imaging [DWI]) to Day 5 (Fluid-Attenuated Inversion Recovery [FLAIR]) [ Time Frame: Baseline, Day 5 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, 24 hrs ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 161
Study Start Date: January 2014
Study Completion Date: April 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01955707

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Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen
  More Information

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01955707     History of Changes
Other Study ID Numbers: 101SK201  EUDRA CT NO: 2013‐001514‐15 
Study First Received: September 30, 2013
Results First Received: February 4, 2016
Last Updated: May 24, 2016
Health Authority: Spain: Spanish Agency of Medicines
Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Additional relevant MeSH terms:
Stroke
Ischemia
Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia
Natalizumab
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2016