Clinical trial NCT02730455: Safety and Efficacy of Intravenous Natalizumab in Acute Ischemic Stroke
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Keywords: Stroke
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2016-04-06
Enrollment: 277
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants With Composite Global Measure of Functional Disability Excellent Outcome at Day 90
timeFrame: Day 90
Secondary outcomes:
measure: Percentage of Participants With Excellent Outcome in mRS Score at Day 90
timeFrame: Day 90
measure: Percentage of Participants With Excellent Outcome in BI Score at Day 90
timeFrame: Day 90
measure: Stroke Impact Scale-16 (SIS-16) Score Using a Repeated Measures Mixed Effects Model at Day 90
timeFrame: Day 90
measure: Montreal Cognitive Assessment (MoCA) Score at Day 90
timeFrame: Day 90
measure: Change From Baseline in National Institute of Health Stroke Scale (NIHSS) Score at Day 90
timeFrame: Baseline, Day 90
measure: Number of Participants Experiencing Adverse Events (AE)
timeFrame: Baseline up to Day 90
measure: Number of Participants Experiencing Serious Adverse Events (SAE)
timeFrame: Baseline up to Day 90
measure: Percentage of Participants With Dose Response at Day 90
timeFrame: Day 90
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Sacramento
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Gainesville
country: United States
facility: Research Site
state: Florida
city: Fort Wayne
country: United States
facility: Research Site
state: Indiana
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Abington
country: United States
facility: Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Altenburg
country: Germany
facility: Research Site
city: Bad Neustadt/Saale
country: Germany
facility: Research Site
city: Bamberg
country: Germany
facility: Research Site
city: Bergisch Gladbach
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Duesseldorf
country: Germany
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Ludwigshafen
country: Germany
facility: Research Site
city: Mannheim
country: Germany
facility: Research Site
city: Minden
country: Germany
facility: Research Site
city: Muenster
country: Germany
facility: Research Site
city: Trier
country: Germany
facility: Research Site
city: Tuebingen
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Albacete
country: Spain
facility: Research Site
city: Badalona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Girona
country: Spain
facility: Research Site
city: Lugo
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valladolid
country: Spain
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
state: Greater London
city: London
country: United Kingdom
facility: Research Site
state: Greater London
city: Harrow
country: United Kingdom
facility: Research Site
state: Middlesex
city: Stoke on Trent
country: United Kingdom
facility: Research Site
state: Staffordshire
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.