Intra-Arterial Bevacizumab as an Adjunct to Middle Meningeal Artery Embolization for Chronic Subdural Hematoma

Overview

This is a Phase 1, open-label, single-center, dose-escalation study evaluating the safety and tolerability of intra-arterial bevacizumab (IA-BEV) given as an adjunct to middle meningeal artery embolization (MMAE) in adults with non-surgical chronic subdural hematoma (cSDH). Up to 18 participants who are already scheduled to undergo MMAE as standard of care will receive a single dose of bevacizumab, delivered directly into the middle meningeal artery immediately before embolization, during the same procedure. Three dose levels (2.0, 3.5, and 5.0 mg/kg) will be tested using a standard 3+3 dose-escalation design to identify the maximum tolerated dose. The study will also collect imaging and blood biomarker data to help understand which patients may benefit most from this combined treatment approach.

Chronic subdural hematoma (cSDH) is a common and growing neurological condition, particularly in older adults, and standard surgical treatment carries meaningful perioperative risk. Middle meningeal artery embolization (MMAE) has emerged as an effective standalone or adjunctive treatment, but a meaningful proportion of patients do not achieve adequate hematoma resolution with embolization alone. Vascular endothelial growth factor (VEGF)-driven angiogenesis within the hematoma membrane is believed to underlie continued hematoma growth and treatment failure. Bevacizumab, an anti-VEGF monoclonal antibody, may interrupt this process when delivered directly into the middle meningeal artery at the time of embolization. This study will enroll up to 18 adults undergoing MMAE as standard of care, assigning them to one of three sequential dose cohorts (2.0, 3.5, or 5.0 mg/kg) of intra-arterial bevacizumab using a 3+3 dose-escalation design. The primary objective is to characterize the safety and tolerability of IA-BEV and identify a maximum tolerated dose. Secondary objectives include volumetric hematoma response, functional and neurological outcomes, and clinical event rates through 180 days. Exploratory objectives include correlating treatment response with Nakaguchi radiographic subtype, dual-energy CT membrane imaging biomarkers, and VEGF concentrations sampled from the middle meningeal artery at the time of the procedure.