Safety and Efficacy of Intravenous Natalizumab in Acute Ischemic Stroke (ACTION2)

December 18, 2018 updated by: Biogen

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
277

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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/Saale, Germany, 97616
        • Research Site
      • Bamberg, Germany, 96049
        • Research Site
      • Bergisch Gladbach, Germany, 51465
        • Research Site
      • Dresden, Germany, 01307
        • Research Site
      • Dresden, Germany, 01067
        • Research Site
      • Duesseldorf, Germany, 40225
        • Research Site
      • Erlangen, Germany, 91054
        • Research Site
      • Frankfurt, Germany, 60528
        • Research Site
      • Hamburg, Germany, 20246
        • Research Site
      • Heidelberg, Germany, 69120
        • Research Site
      • Leipzig, Germany, 04103
        • Research Site
      • Ludwigshafen, Germany, 67063
        • Research Site
      • Mannheim, Germany, 68167
        • Research Site
      • Minden, Germany, 32429
        • Research Site
      • Muenster, Germany, 48149
        • Research Site
      • Trier, Germany, 54292
        • Research Site
      • Tuebingen, Germany, 72076
        • Research Site
      • Ulm, Germany, 89081
        • Research Site
  • Spain
      • Albacete, Spain, 02008
        • Research Site
      • Badalona, Spain, 08916
        • Research Site
      • Barcelona, Spain, 08035
        • Research Site
      • Barcelona, Spain, 08003
        • Research Site
      • Girona, Spain, 17007
        • Research Site
      • Lugo, Spain, 27003
        • Research Site
      • Madrid, Spain, 28034
        • Research Site
      • Madrid, Spain, 28007
        • Research Site
      • Malaga, Spain, 29010
        • Research Site
      • Sevilla, Spain, 41013
        • Research Site
      • Sevilla, Spain, 41017
        • Research Site
      • Valladolid, Spain, 47005
        • Research Site
  • United Kingdom
    • Greater London
      • London, Greater London, United Kingdom, W6 8RF
        • Research Site
      • London, Greater London, United Kingdom, SW17 0QT
        • Research Site
    • Middlesex
      • Harrow, Middlesex, United Kingdom, HA1 3UJ
        • Research Site
    • Staffordshire
      • Stoke on Trent, Staffordshire, United Kingdom, ST4 6QG
        • Research Site
  • United States
    • California
      • Los Angeles, California, United States, 90024
        • Research Site
      • Sacramento, California, United States, 95816
        • Research Site
      • San Diego, California, United States, 92103
        • Research Site
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Research Site
    • Florida
      • Gainesville, Florida, United States, 32611
        • Research Site
    • Indiana
      • Fort Wayne, Indiana, United States, 46845
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Research Site
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Research Site
    • New York
      • New York, New York, United States, 10032
        • Research Site
    • North Carolina
      • Durham, North Carolina, United States, 19104
        • Research Site
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Research Site
    • Oregon
      • Portland, Oregon, United States, 97239
        • Research Site
      • Portland, Oregon, United States, 97225
        • Research Site
      • Portland, Oregon, United States, 97201
        • Research Site
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Research Site
      • Philadelphia, Pennsylvania, United States, 19104
        • Research Site
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Research Site
    • Tennessee
      • Knoxville, Tennessee, United States, 37920-6999
        • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: natalizumab high dose
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.
Drug: natalizumab
Administered as specified in the treatment arm
Other Names:
  • BG00002
EXPERIMENTAL: natalizumab low dose
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.
Drug: natalizumab
Administered as specified in the treatment arm
Other Names:
  • BG00002
EXPERIMENTAL: Placebo
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.
Drug: Placebo
Matched placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Composite Global Measure of Functional Disability Excellent Outcome at Day 90
Time Frame: 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.
Day 90

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Excellent Outcome in mRS Score at Day 90
Time Frame: 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.
Day 90
Percentage of Participants With Excellent Outcome in BI Score at Day 90
Time Frame: 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.
Day 90
Stroke Impact Scale-16 (SIS-16) Score Using a Repeated Measures Mixed Effects Model at Day 90
Time Frame: 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.
Day 90
Montreal Cognitive Assessment (MoCA) Score at Day 90
Time Frame: 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).
Day 90
Change From Baseline in National Institute of Health Stroke Scale (NIHSS) Score at Day 90
Time Frame: Baseline, 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.
Baseline, Day 90
Number of Participants Experiencing Adverse Events (AE)
Time Frame: Baseline up to Day 90
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.
Baseline up to Day 90
Number of Participants Experiencing Serious Adverse Events (SAE)
Time Frame: Baseline up to Day 90
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.
Baseline up to Day 90
Percentage of Participants With Dose Response at Day 90
Time Frame: Day 90
Percentage of participants with dose response was evaluated in proportion of excellent outcome on mRS and BI.
Day 90

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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 (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 18, 2016

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 20, 2017

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 20, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 10, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 1, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 6, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 8, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 18, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 101SK202
  • 2015-004783-11 (EUDRACT_NUMBER)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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