Phase 2a Study Of Elezanumab In Patients With Acute Ischemic Stroke

Introduction: Treatment of acute ischemic stroke focuses on reperfusion but is limited by timing and other exclusions, and despite intervention, patients may sustain residual neurologic impairment. In addition to initial excitotoxic reactions following occlusion, upregulation of factors such as repulsive guidance molecule A (RGMa) inhibits cell survival and neuronal repair in infarcted regions. In vivo neutralization of RGMa is associated with decreased lesion size, reduced glial scarring, and enhanced functional recovery in animal models of cerebral artery occlusion; thus, RGMa suppression represents a novel therapeutic target due to its potential protective and restorative mechanisms. Elezanumab is an investigational monoclonal antibody that binds specifically to RGMa and is being evaluated for its function after ischemic stroke. Methods: Elezanumab in Acute Ischemic Stroke (EAISE) is a 52-week, phase 2a, randomized, double-blind, placebo-controlled study evaluating safety, efficacy, and pharmacokinetics of elezanumab in patients with acute ischemic stroke (NCT04309474). Patients will be randomized 1:1 within 23 hours since “last known normal” to receive elezanumab or placebo and every 4 weeks thereafter through week 48. Patients must be aged 30-90 years with a clinical diagnosis of acute ischemic stroke in anterior circulation and have a National Institutes of Health Stroke Scale (NIHSS) total score of 7 to 21. Patients who receive tissue plasminogen activator or endovascular therapy will be eligible if they continue to exhibit an NIHSS of 7 to 21 after treatment. Patients with evidence of seizure on stroke onset and history of repeated episodes of complex migraines will be excluded. Results: Projected enrollment is 120 patients across 45 sites in multiple countries. Primary endpoint is the NIHSS total score throughout the treatment period. Secondary endpoint is a favorable outcome based on the modified Rankin Scale, defined as a score of 0-2 at week 52. Exploratory outcomes include activities of daily living, cognition, mood, and fluid and imaging biomarkers. Conclusion: This phase 2 study will evaluate safety and efficacy of elezanumab, a novel therapeutic intervention to improve neurological recovery after acute ischemic stroke.