Clinical trial NCT01955707: Effect of Natalizumab on Infarct Volume in Acute Ischemic Stroke
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2013-10-07
Enrollment: 161
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
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 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.


Eligibility criteria: Key Inclusion Criteria:

* 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:

* 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.
* 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.

Primary outcomes:
measure: Change in Infarct Volume From Baseline (Diffusion-Weighted Imaging [DWI]) to Day 5 (Fluid-Attenuated Inversion Recovery [FLAIR])
timeFrame: Baseline, Day 5
Secondary outcomes:
measure: Change in Infarct Volume From Baseline (DWI) to 24 Hours (FLAIR)
timeFrame: Baseline, 24 hrs
measure: Change in Infarct Volume From Baseline (DWI) to Day 30 (FLAIR)
timeFrame: Baseline, Day 30
measure: Change in Infarct Volume From 24 Hours (FLAIR) to Day 5 (FLAIR)
timeFrame: 24 hours, Day 5
measure: Change in Infarct Volume From 24 Hours (FLAIR) to Day 30 (FLAIR)
timeFrame: 24 hours, Day 30
measure: Change in Infarct Volume From Day 5 (FLAIR) to Day 30 (FLAIR)
timeFrame: Day 5, Day 30
measure: Change in National Institute of Health Stroke Scale (NIHSS) Score From Baseline to 24 Hours, Day 5, Day 30, and Day 90
timeFrame: Baseline, 24 hours, Day 5, Day 30, Day 90
measure: Modified Rankin Scale (mRS) Distribution at Day 5, Day 30, and Day 90
timeFrame: Day 5, Day 30, and Day 90
measure: Barthel Index at Day 5, Day 30, and Day 90
timeFrame: Day 5, Day 30, and Day 90
measure: Number of Participants Who Experience Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Day 90 ± 5 days
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Research Site
state: California
city: Gainesville
country: United States
facility: Research Site
state: Florida
city: Kansas City
country: United States
facility: Research Site
state: Kansas
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Golden Valley
country: United States
facility: Research Site
state: Minnesota
city: St. Louis
country: United States
facility: Research Site
state: Missouri
city: Lake Success
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Akron
country: United States
facility: Research Site
state: Ohio
city: Dayton
country: United States
facility: Research Site
state: Ohio
city: Toledo
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Tualatin
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Altenburg
country: Germany
facility: Research Site
city: Bad Neustadt
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bonn
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: Hannover
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Idar-Oberstein
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Ludwigshafen
country: Germany
facility: Research Site
city: Ludwigshafen
country: Germany
facility: Research Site
city: Mannheim
country: Germany
facility: Research Site
city: Trier
country: Germany
facility: Research Site
city: Tübingen
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: Barakaldo
country: Spain
facility: Research Site
city: Barcelona
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: Madrid
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Valladolid
country: Spain
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.