Safety and Efficacy of Intravenous Natalizumab in Acute Ischemic Stroke

NCT02730455 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 101SK2022015-004783-11
• Study Type: interventional
• Target: 277
• Locations: 4 countries
• Sites: 53

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

Conditions

Acute Ischemic Stroke

Keywords

Stroke

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 90

Secondary Outcomes (8)

• Percentage of Participants With Excellent Outcome in mRS Score at Day 90

  Day 90

• Percentage of Participants With Excellent Outcome in BI Score at Day 90

  Day 90

• Stroke Impact Scale-16 (SIS-16) Score Using a Repeated Measures Mixed Effects Model at Day 90

  Day 90

• Montreal Cognitive Assessment (MoCA) Score at Day 90

  Day 90

• Change From Baseline in National Institute of Health Stroke Scale (NIHSS) Score at Day 90

  Baseline, Day 90

Study Arms (3)

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.

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.

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.

Drug: Placebo

Interventions

natalizumab DRUG

Administered as specified in the treatment arm

Also known as: BG00002

natalizumab high dose; natalizumab low dose

Placebo DRUG

Matched placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Lacunar or isolated brainstem or cerebellar stroke based on clinical assessment and available acute imaging studies performed under the standard of care.
• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (53)

Research Site

Los Angeles, California, 90024, United States

Location

Research Site

Sacramento, California, 95816, United States

Location

Research Site

San Diego, California, 92103, United States

Location

Research Site

Washington D.C., District of Columbia, 20007, United States

Location

Research Site

Gainesville, Florida, 32611, United States

Location

Research Site

Fort Wayne, Indiana, 46845, United States

Location

Research Site

Boston, Massachusetts, 02114, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

New York, New York, 10032, United States

Location

Research Site

Durham, North Carolina, 19104, United States

Location

Research Site

Columbus, Ohio, 43210, United States

Location

Research Site

Portland, Oregon, 97201, United States

Location

Research Site

Portland, Oregon, 97225, United States

Location

Research Site

Portland, Oregon, 97239, United States

Location

Research Site

Abington, Pennsylvania, 19001, United States

Location

Research Site

Philadelphia, Pennsylvania, 19104, United States

Location

Research Site

Charleston, South Carolina, 29425, United States

Location

Research Site

Knoxville, Tennessee, 37920-6999, United States

Location

Research Site

Altenburg, 04600, Germany

Location

Research Site

Bad Neustadt/Saale, 97616, Germany

Location

Research Site

Bamberg, 96049, Germany

Location

Research Site

Bergisch Gladbach, 51465, Germany

Location

Research Site

Dresden, 01067, Germany

Location

Research Site

Dresden, 01307, Germany

Location

Research Site

Düsseldorf, 40225, Germany

Location

Research Site

Erlangen, 91054, Germany

Location

Research Site

Frankfurt, 60528, Germany

Location

Research Site

Hamburg, 20246, Germany

Location

Research Site

Heidelberg, 69120, Germany

Location

Research Site

Leipzig, 04103, Germany

Location

Research Site

Ludwigshafen, 67063, Germany

Location

Research Site

Mannheim, 68167, Germany

Location

Research Site

Minden, 32429, Germany

Location

Research Site

Münster, 48149, Germany

Location

Research Site

Trier, 54292, Germany

Location

Research Site

Tübingen, 72076, Germany

Location

Research Site

Ulm, 89081, Germany

Location

Research Site

Albacete, 02008, Spain

Location

Research Site

Badalona, 08916, Spain

Location

Research Site

Barcelona, 08003, Spain

Location

Research Site

Barcelona, 08035, Spain

Location

Research Site

Girona, 17007, Spain

Location

Research Site

Lugo, 27003, Spain

Location

Research Site

Madrid, 28007, Spain

Location

Research Site

Madrid, 28034, Spain

Location

Research Site

Málaga, 29010, Spain

Location

Research Site

Seville, 41013, Spain

Location

Research Site

Seville, 41017, Spain

Location

Research Site

Valladolid, 47005, Spain

Location

Research Site

London, Greater London, SW17 0QT, United Kingdom

Location

Research Site

London, Greater London, W6 8RF, United Kingdom

Location

Research Site

Harrow, Middlesex, HA1 3UJ, United Kingdom

Location

Research Site

Stoke-on-Trent, Staffordshire, ST4 6QG, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 32591475 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

Natalizumab

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Biogen Study Medical Director
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2016
• First Posted: April 6, 2016
• Study Start: July 18, 2016
• Primary Completion: November 20, 2017
• Study Completion: November 20, 2017
• Last Updated: January 8, 2019
• Results First Posted: January 8, 2019

Record last verified: 2018-12

Locations

US (18); DE (19); GB (4); ES (12)