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Trial record 1 of 2 for:    natalizumab | stroke
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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

Tracking Information
First Submitted Date  ICMJE March 10, 2016
First Posted Date  ICMJE April 6, 2016
Results First Submitted Date  ICMJE October 18, 2018
Results First Posted Date  ICMJE January 8, 2019
Last Update Posted Date January 8, 2019
Actual Study Start Date  ICMJE July 18, 2016
Actual Primary Completion Date November 20, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 18, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 1, 2016)
  • Composite global measure of functional disability based on a score of 0 or 1 on the modified Rankin Scale (mRS) [ Time Frame: Day 5 to Day 90 ]
    The mRS measures independence, 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. The mRS takes less than 5 minutes to administer and will be completed by a telephone interview for any participants who fail to attend their Day 90 follow-up or early termination visit.
  • Score of ≥95 on the Barthel Index (BI) [ Time Frame: Day 5 to Day 90 ]
    The BI consists of 10 items that measure a person'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. Each item is measured on a 10 point scale with a maximum score of 100 with higher scores indicating higher independence of the participant in performing these tasks. The BI takes less than 5 minutes to administer.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2018)
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2016)
  • modified Rankin Scale (mRS) score [ Time Frame: Day 5 to Day 90 ]
  • Barthel Index (BI) score [ Time Frame: Day 5 to Day 90 ]
  • Stroke Impact Scale-16 (SIS-16) score [ Time Frame: Day 5 to Day 90 ]
    The SIS-16 is a 16-item physical dimension instrument that measures 16 physical aspects rated on a scale of 1 (could not do at all) to 5 (not difficult at all). The SIS-16 takes less than 5 minutes to administer and will be completed by a telephone interview for any participants who fail to attend their Day 90 follow-up or early termination visit.
  • Montreal Cognitive Assessment (MoCA) score [ Time Frame: Day 5 to Day 90 ]
    The MoCA is a global cognitive screening test which screens 8 domains of psychometric properties: visuospatial/executive, naming, memory, attention, language, abstraction, delayed recall, and orientation with a highest score of 30 points. This assessment takes approximately 10 minutes to administer.
  • Number of participants experiencing adverse events (AE) [ Time Frame: Baseline to Day 90 ]
  • Number of Participants Experiencing Serious Adverse Events (SAE) [ Time Frame: Baseline to Day 90 ]
  • National Institute of Health Stroke Scale (NIHSS) score [ Time Frame: Baseline to Day 90 ]
    The NIHSS is used to assess the effects of acute cerebral infarction. This score 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). This is a 15 item questionnaire on a rating of 3 to 5 grades, with 0 as normal and a maximum possible of 42 for all items and takes about 10 minutes to administer.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Intravenous Natalizumab in Acute Ischemic Stroke
Official Title  ICMJE 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
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Acute Ischemic Stroke
Intervention  ICMJE
  • Drug: natalizumab
    Administered as specified in the treatment arm
    Other Name: BG00002
  • Drug: Placebo
    Matched placebo
Study Arms  ICMJE
  • 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.
    Intervention: Drug: natalizumab
  • 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.
    Intervention: Drug: natalizumab
  • 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.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 18, 2018)
277
Original Estimated Enrollment  ICMJE
 (submitted: April 1, 2016)
240
Actual Study Completion Date  ICMJE November 20, 2017
Actual Primary Completion Date November 20, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02730455
Other Study ID Numbers  ICMJE 101SK202
2015-004783-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Biogen
Study Sponsor  ICMJE Biogen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Biogen
PRS Account Biogen
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP