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

Biogen

Status and phase: Completed; Phase 2

Conditions: Acute Ischemic Stroke

Treatments: Drug: Placebo; Drug: natalizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02730455

101SK202

2015-004783-11 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 277 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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277 participants in 3 patient groups

natalizumab high dose

Experimental group

Description:

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.

Treatment:

Drug: natalizumab

natalizumab low dose

Experimental group

Description:

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.

Treatment:

Drug: natalizumab

Placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo