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

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ClinicalTrials.gov Identifier: NCT02730455
Recruitment Status : Completed
First Posted : April 6, 2016
Results First Posted : January 8, 2019
Last Update Posted : January 8, 2019
Sponsor:
Information provided by (Responsible Party):
Biogen

Brief 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. 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

Condition or disease Intervention/treatment Phase
Acute Ischemic Stroke Drug: natalizumab Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 277 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : July 18, 2016
Actual Primary Completion Date : November 20, 2017
Actual Study Completion Date : November 20, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Natalizumab

Arm Intervention/treatment
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 Name: 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 Name: 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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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).

  5. 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.

  6. 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.

  7. 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.

  8. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02730455


  Show 53 Study Locations
Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen
  Study Documents (Full-Text)

Documents provided by Biogen:
Study Protocol  [PDF] May 19, 2017
Statistical Analysis Plan  [PDF] December 5, 2017


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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02730455     History of Changes
Other Study ID Numbers: 101SK202
2015-004783-11 ( EudraCT Number )
First Posted: April 6, 2016    Key Record Dates
Results First Posted: January 8, 2019
Last Update Posted: January 8, 2019
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Biogen:
Stroke

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