Acute Ischemic StrokePhase 2ACTION2NCT02730455
Safety and Efficacy of Intravenous Natalizumab in Acute Ischemic Stroke
A Phase 2 study testing natalizumab in people with Acute Ischemic Stroke, run by Biogen at 53 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 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
- 277 participants
- Where
- 53 sitesin 4 countries
- Study dates
- 18 Jul 2016to 20 Nov 2017
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
53 sites in 4 countries.
53 sites in 4 countries
Germany19 sites
Research Site
Altenburg, 04600
Research Site
Bad Neustadt/Saale, 97616
Research Site
Bamberg, 96049
Research Site
Bergisch Gladbach, 51465
Research Site
Dresden, 01067
Research Site
Dresden, 01307
Research Site
Düsseldorf, 40225
Research Site
Erlangen, 91054
Research Site
Frankfurt, 60528
Research Site
Hamburg, 20246
Research Site
Heidelberg, 69120
Research Site
Leipzig, 04103
Research Site
Ludwigshafen, 67063
Research Site
Mannheim, 68167
Research Site
Minden, 32429
Research Site
Münster, 48149
Research Site
Trier, 54292
Research Site
Tübingen, 72076
Research Site
Ulm, 89081
United States18 sites
Research Site
Abington, Pennsylvania, 19001
Research Site
Boston, Massachusetts, 02114
Research Site
Charleston, South Carolina, 29425
Research Site
Columbus, Ohio, 43210
Research Site
Durham, North Carolina, 19104
Research Site
Fort Wayne, Indiana, 46845
Research Site
Gainesville, Florida, 32611
Research Site
Knoxville, Tennessee, 37920-6999
Research Site
Los Angeles, California, 90024
Research Site
New York, New York, 10032
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Portland, Oregon, 97201
Research Site
Portland, Oregon, 97225
Research Site
Portland, Oregon, 97239
Research Site
Sacramento, California, 95816
Research Site
San Diego, California, 92103
Research Site
St Louis, Missouri, 63110
Research Site
Washington D.C., District of Columbia, 20007
Spain12 sites
Research Site
Albacete, 02008
Research Site
Badalona, 08916
Research Site
Barcelona, 08003
Research Site
Barcelona, 08035
Research Site
Girona, 17007
Research Site
Lugo, 27003
Research Site
Madrid, 28007
Research Site
Madrid, 28034
Research Site
Málaga, 29010
Research Site
Seville, 41013
Research Site
Seville, 41017
Research Site
Valladolid, 47005
United Kingdom4 sites
Research Site
Harrow, Middlesex, HA1 3UJ
Research Site
London, Greater London, SW17 0QT
Research Site
London, Greater London, W6 8RF
Research Site
Stoke-on-Trent, Staffordshire, ST4 6QG
About this study
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
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
- Conditions
- Acute Ischemic Stroke
- Being tested
- natalizumab, Placebo
- Keywords
- Stroke
- Medical subject headings
- Ischemic Stroke, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
natalizumabDrug
Also called BG00002
Administered as specified in the treatment arm
PlaceboDrug
Matched placebo
| Study group | Role | What they receive |
|---|---|---|
| natalizumab high dose | Experimental | 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. Receives: Drug: natalizumab |
| natalizumab low dose | Experimental | 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. Receives: Drug: natalizumab |
| Placebo | Experimental | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 90
Secondary outcomes (8)
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.
Measured: Day 90
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.
Measured: Day 90
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.
Measured: Day 90
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).
Measured: Day 90
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.
Measured: Baseline, Day 90
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.
Measured: Baseline up to Day 90
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.
Measured: Baseline up to Day 90
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.
Measured: Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2016 (estimated)
- Study start18 Jul 2016
- Primary completion20 Nov 2017
- Study completion20 Nov 2017
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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 277 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
- NCT02730455
- Sponsor's protocol ID
- 101SK202
- Other IDs
- 2015-004783-11, 2015
- Acronym
- ACTION2
- Status last verified
- Dec 2018
- First submitted
- 10 Mar 2016
- Last updated
- 8 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 32591475
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02730455
- Acronym / sponsor ID
- ACTION2 / 101SK202
- Conditions
- Acute Ischemic Stroke
- Keywords
- Stroke
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 277 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 18 Jul 2016 (actual)
- Primary completion
- 20 Nov 2017 (actual)
- Study completion
- 20 Nov 2017 (actual)
- First posted
- 6 Apr 2016 (estimated)
- Results
- Posted 8 Jan 2019
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 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| natalizumab high dose | Experimental | Drug: natalizumabSingle 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. |
| natalizumab low dose | Experimental | Drug: natalizumabSingle 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. |
| Placebo | Experimental | Drug: PlaceboSingle 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (10 listed)
- 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
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: BG00002Administered as specified in the treatment arm | Drug | natalizumab high dose, natalizumab low dose |
| PlaceboMatched placebo | Drug | Placebo |
Primary outcome
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.
8 secondary outcomes
Percentage of Participants With Excellent Outcome in mRS Score at Day 90
Time frame: Day 90
Percentage of Participants With Excellent Outcome in BI Score at Day 90
Time frame: Day 90
Stroke Impact Scale-16 (SIS-16) Score Using a Repeated Measures Mixed Effects Model at Day 90
Time frame: Day 90
Montreal Cognitive Assessment (MoCA) Score at Day 90
Time frame: Day 90
Change From Baseline in National Institute of Health Stroke Scale (NIHSS) Score at Day 90
Time frame: Baseline, Day 90
Number of Participants Experiencing Adverse Events (AE)
Time frame: Baseline up to Day 90
Number of Participants Experiencing Serious Adverse Events (SAE)
Time frame: Baseline up to Day 90
Percentage of Participants With Dose Response at Day 90
Time frame: Day 90
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32591475Elkind 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.
Related trials for Acute Ischemic Stroke
Not yet recruiting
Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke
Acute Ischemic Stroke
RecruitingObservational study
ELATE Study: Evaluating Large-vessel Acute Thrombectomy in Extended Time Window
Acute Ichemic Stroke
Not yet recruiting
Selective Intra-Arterial Hypothermia After Endovascular Treatment for Acute Basilar Artery Occlusion
Acute Ischemic Stroke, Basilar Artery Occlusion
RecruitingObservational study
Continuous Dual Aspiration Technique With Zoom System for Stroke
Ischemic Stroke, Acute Stroke
Not yet recruitingPhase 2/3
A Multicenter, Open-label, Randomized, Non-inferiority Clinical Trial With Blinded Endpoint Assessment of Early Tirofiban After Intravenous Thrombolysis in Acute Ischemic Stroke
Acute Ischemic Stroke
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
53 sites in 4 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 53 sites in 4 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 8 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in Germany, United States, Spain, United Kingdom. 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. 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 8 Jan 2019). 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?
Percentage of Participants With Composite Global Measure of Functional Disability Excellent Outcome at Day 90 (time frame: Day 90). 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 NCT02730455, 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 8 Jan 2019.