A Safety and Efficacy Study of Intravenous (IV) Elezanumab Assessing Change in Neurologic Function in Adult Participants With Acute Ischemic Stroke

Study Overview
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Brief Summary
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Stroke is one of the leading causes death and major functional disability worldwide. Treatment options for acute stroke are limited with many patients having residual neurologic impairment. The purpose of this study is to evaluate the safety and efficacy of elezanumab and assess change in neurologic function in participants following an acute ischemic stroke. Elezanumab is an investigational drug being developed for the treatment of acute ischemic stroke. This 52-week study is double-blinded', which means that neither the participants nor the study doctors will know who will be given elezanumab and who will be given placebo (does not contain treatment drug). Participants will be assigned to one of two groups, called treatment arms. Participants in one arm will receive elezanumab and participants in the other arm will receive placebo. There is a 1 in 2 chance that participants will be assigned to placebo. Approximately 120 subjects will be enrolled in 45 sites worldwide. Participants will be randomized to elezanumab or placebo by intravenous (IV) infusion within 24 hours of last known normal (time when the participant was last known to be without signs and symptoms of the current stroke) and every 4 weeks thereafter for 48 weeks for a total of 13 doses. There may be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of elezanumab will be checked by medical assessments, blood tests, evaluation of side effects, and completion of questionnaires.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Proof-of-Concept Study to Assess the Safety and Efficacy of Elezanumab in Acute Ischemic Stroke

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: Elezanumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of acute ischemic stroke, supported by acute brain computed tomography (CT) or magnetic resonance imaging (MRI) consistent with the clinical diagnosis. Able to randomize within 24 hours of last known normal. National Institute of Health Stroke Scale (NIHSS) total score of 7 to 21, inclusive. Participants or their legally authorized representative confirms that prior to index stroke, no significant impairment in participant's ability to perform activities of daily living without assistance. Exclusion Criteria: Evidence of severe stroke on imaging based on available acute imaging studies performed under the standard of care. Evidence of acute seizure at the onset of index stroke without conclusive imaging of ischemic stroke. Evidence of acute myocardial infarction. Symptoms are considered likely to resolve within the subsequent few hours (e.g., transient ischemic attack [TIA]). Known history prior to randomization of clinically significant medical conditions (other than current acute ischemic stroke) or any other reason, including any physical, psychological, or psychiatric condition that in the investigator's opinion would compromise the safety or interfere with the participant's participation in this study. Known medical history of repeated episodes of complex migraine. Participants with history of complex migraine, but with imaging conclusively demonstrating an acute ischemic stroke are still allowed. Female who is pregnant, breastfeeding, or considering becoming pregnant during the study or for within 39 weeks (5 half-lives) after the last dose of study drug. Known receipt of any investigational product within 30 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of study drug. No current enrollment in another interventional clinical study, including pharmacologic and behavioral interventional studies.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elezanumab<br>Participants will receive elezanumab dose A | Drug: Elezanumab<br>* Intravenous (IV) infusion<br>* Other names: ABT-555;|
| Placebo Comparator: Placebo<br>Participants will receive placebo for elezanumab | Drug: Placebo<br>* Intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institutes of Health Stroke Scale (NIHSS) Total Score During the Treatment Period | The National Institutes of Health Stroke Scale (NIHSS) is a neurological examination used to quantitatively measure the severity of acute stroke by evaluating impact of cerebral infarction on level of consciousness, gaze, visual field, facial palsy, motor ability of arm and leg, limb ataxia, sensation, language, dysarthria, and extinction/inattention. Domains are scored on a scale of 0 to 2, 0 to 3, or 0 to 4, for a total range of 0 -42 points with higher scores indicating impairment. | Week 0 through Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Status based on Modified Rankin Scale (mRS) | The mRS is used to assess participant's disability and functional dependence. It is a 6-point scale ranging from 0 (no symptoms) to 5 (severe disability), with additional rating of 6 if the participant is deceased. | Week 0 through Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Ischemic Stroke, ABT-555, Elezanumab, EAISE