Acute Ischemic StrokePhase 2ACTIONNCT01955707
Effect of Natalizumab on Infarct Volume in Acute Ischemic Stroke
A Phase 2 study testing natalizumab in people with Acute Ischemic Stroke, run by Biogen at 50 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Acute Ischemic Stroke
- What is being tested?
- natalizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 161 participants
- Where
- 50 sitesin 3 countries
- Study dates
- Jan 2014to Apr 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
50 sites in 3 countries.
50 sites in 3 countries
United States19 sites
Research Site
Akron, Ohio
Research Site
Boston, Massachusetts, 02114
Research Site
Charlottesville, Virginia
Research Site
Dallas, Texas
Research Site
Dayton, Ohio, 45409
Research Site
Durham, North Carolina, 27710
Research Site
Gainesville, Florida
Research Site
Golden Valley, Minnesota, 55422
Research Site
Kansas City, Kansas, 66160
Research Site
Lake Success, New York
Research Site
Milwaukee, Wisconsin
Research Site
Nashville, Tennessee
Research Site
New York, New York, 10032
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Portland, Oregon
Research Site
San Diego, California
Research Site
St Louis, Missouri, 63110
Research Site
Toledo, Ohio
Research Site
Tualatin, Oregon, 97062
Germany17 sites
Research Site
Altenburg, 04600
Research Site
Bad Neustadt an der Saale, 97616
Research Site
Berlin, 12203
Research Site
Bonn
Research Site
Düsseldorf, 40225
Research Site
Erlangen, 91054
Research Site
Frankfurt, 60528
Research Site
Hanover
Research Site
Heidelberg, 69120
Research Site
Idar-Oberstein, 55743
Research Site
Leipzig, 04103
Research Site
Ludwigshafen, 67063
Research Site
Ludwigshafen
Research Site
Mannheim
Research Site
Trier, 54290
Research Site
Tübingen, 72076
Research Site
Ulm
Spain14 sites
Research Site
Albacete, 02006
Research Site
Badalona, 8916
Research Site
Barakaldo
Research Site
Barcelona, 8003
Research Site
Barcelona, 8035
Research Site
Barcelona, 8036
Research Site
Girona, 17007
Research Site
Madrid, 28034
Research Site
Pamplona, 31008
Research Site
Santiago de Compostela, 15706
Research Site
Seville, 41009
Research Site
Seville, 41013
Research Site
Valencia
Research Site
Valladolid, 47005
About this study
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
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.
- Conditions
- Acute Ischemic Stroke
- Being tested
- natalizumab, Placebo
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
natalizumabDrug
Also called Tysabri, BG00002
Administered as described in the treatment arm
PlaceboDrug
Matched placebo
| Study group | Role | What they receive |
|---|---|---|
| natalizumab | Experimental | 300 mg single intravenous (IV) injection Receives: Drug: natalizumab |
| Placebo | Placebo comparator | A single IV dose of placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Day 5
Secondary outcomes (9)
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.
Measured: Baseline, 24 hrs
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.
Measured: Baseline, Day 30
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.
Measured: 24 hours, Day 5
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.
Measured: 24 hours, Day 30
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.
Measured: Day 5, Day 30
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.
Measured: Baseline, 24 hours, Day 5, Day 30, Day 90
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.
Measured: Day 5, Day 30, and Day 90
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.
Measured: Day 5, Day 30, and Day 90
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.
Measured: Up to Day 90 ± 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2013 (estimated)
- Study startJan 2014
- Primary completionFeb 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 161 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01955707
- Sponsor's protocol ID
- 101SK201
- Other IDs
- EUDRA CT NO: 2013-001514-15
- Acronym
- ACTION
- Status last verified
- May 2016
- First submitted
- 30 Sep 2013
- Last updated
- 1 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 28229893
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01955707
- Acronym / sponsor ID
- ACTION / 101SK201
- Conditions
- Acute Ischemic Stroke
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 161 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- Jan 2014
- Primary completion
- Feb 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 7 Oct 2013 (estimated)
- Results
- Posted 1 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| natalizumab | Experimental | Drug: natalizumab300 mg single intravenous (IV) injection |
| Placebo | Placebo comparator | Drug: PlaceboA single IV dose of placebo |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| natalizumabAlso: Tysabri, BG00002Administered as described in the treatment arm | Drug | natalizumab |
| PlaceboMatched placebo | Drug | Placebo |
Primary outcome
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.
9 secondary outcomes
Change in Infarct Volume From Baseline (DWI) to 24 Hours (FLAIR)
Time frame: Baseline, 24 hrs
Change in Infarct Volume From Baseline (DWI) to Day 30 (FLAIR)
Time frame: Baseline, Day 30
Change in Infarct Volume From 24 Hours (FLAIR) to Day 5 (FLAIR)
Time frame: 24 hours, Day 5
Change in Infarct Volume From 24 Hours (FLAIR) to Day 30 (FLAIR)
Time frame: 24 hours, Day 30
Change in Infarct Volume From Day 5 (FLAIR) to Day 30 (FLAIR)
Time frame: Day 5, 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: Baseline, 24 hours, Day 5, Day 30, Day 90
Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90
Time frame: Day 5, Day 30, and Day 90
Barthel Index at Day 5, Day 30, and Day 90
Time frame: Day 5, Day 30, and Day 90
Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to Day 90 ± 5 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28229893Elkins 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Biogen
50 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing natalizumab in people with Acute Ischemic Stroke, run by Biogen at 50 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 50 sites in United States, Germany, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Infarct Volume From Baseline (Diffusion-Weighted Imaging [DWI]) to Day 5 (Fluid-Attenuated Inversion Recovery [FLAIR]) (time frame: Baseline, Day 5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01955707, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2016.