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

NCT07729098 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: SM-UMB
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Chronic Subdural Hematoma

Keywords

bevacizumab; middle meningeal artery embolization; intra-arterial chemotherapy; VEGF

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities

  Incidence of dose-limiting toxicities probably or definitely related to IA-BEV

  30 Days of Treatment

• Incidence of SAE's

  Incidence of dose-limiting toxicities (DLTs) and serious adverse events (SAEs) probably or definitely related to IA-BEV

  30 Days of Study Treatment

Secondary Outcomes (7)

• Incidence of acute neurological worsening

  Within 24 hours post-procedure

• Volumetric change in cSDH size

  30, 90, and 180 days

• Rates of surgical rescue, unplanned hospitalization, neurological death, and all-cause mortality

  Through 6 months

• Functional status

  30, 90, and 180 days

• Neurological Status

  30 and 180 days

Other Outcomes (3)

• Distribution of Nakaguchi radiographic subtype and association with treatment response

  Baseline through 180 days

• Dual-energy CT (DECT)-derived membrane biomarkers (volume, maturity grade, iodine leakage) as predictors of outcome

  Baseline through 180 days

• MMA-to-peripheral VEGF concentration ratio as a molecular biomarker of treatment response

  Day of procedure

Study Arms (1)

IA-BEV + MMAE

EXPERIMENTAL

Participants receive intra-arterial bevacizumab (dose per assigned cohort: 2.0, 3.5, or 5.0 mg/kg) via selective MMA microcatheter infusion immediately prior to standard-of-care middle meningeal artery embolization, within the same procedural session.

Drug: Bevacizumab (intra-arterial)

Interventions

Bevacizumab (intra-arterial) DRUG

Single intra-arterial infusion of bevacizumab (reference product or FDA-approved biosimilar) at 2.0, 3.5, or 5.0 mg/kg, delivered via microcatheter into the middle meningeal artery over 5-10 minutes, immediately before MMAE.

IA-BEV + MMAE

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-85 years
• Scheduled to undergo MMAE as standard of care for cSDH, no concurrent surgical evacuation planned (prior surgery for the target cSDH allowed if ≥14 days elapsed)
• Radiographically confirmed cSDH meeting specified unilateral/bilateral density criteria
• cSDH volume 20-100 cc
• Midline shift \<8 mm
• Markwalder Grade 1 or 2
• Subject or LAR able to provide written informed consent

You may not qualify if:

• Requires immediate/urgent surgical evacuation
• Prior large craniotomy, membranectomy, or MMAE for the current target cSDH
• Life expectancy \<1 year
• Uncontrolled bleeding disorder (INR \>1.7, aPTT \>35s, platelets \<100,000/μL)
• Concurrent intracranial hemorrhage outside the target subdural space
• Persistent neurological deficit from another acute/chronic neurological condition
• Pregnancy or lactation
• Known/suspected intracranial neoplasm or mass lesion
• Active alcohol/substance use disorder within 12 months
• Baseline mRS ≥3
• Uncontrolled severe hypertension (SBP \>220 or DBP \>120, or IV antihypertensive need within 24h pre-procedure)
• Thromboembolic event within 6 months (DVT, PE, TIA, stroke)
• Contraindication to VTE prophylaxis
• eGFR \<60 mL/min/1.73m² or acute kidney injury at screening
• Known hypersensitivity to bevacizumab or its components

Sponsors & Collaborators

• Dheeraj Gandhi: lead

MeSH Terms

Conditions

Hematoma, Subdural, Chronic

Interventions

Bevacizumab; Infusions, Intra-Arterial

Condition Hierarchy (Ancestors)

Hematoma, Subdural; Intracranial Hemorrhage, Traumatic; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Vascular Diseases; Cardiovascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hematoma; Hemorrhage; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Infusions, Parenteral; Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Kaitlyn Henry, MS

CONTACT

410-328-0939; khenry@som.umaryland.edu

Najme Hosseini, MD

CONTACT

410-328-4068; nhosseini@som.umaryland.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MBBS, MD, FACR

Model Details: Sequential 3+3 dose-escalation cohorts (not separate arms)

Study Record Dates

• First Submitted: July 16, 2026
• First Posted: July 27, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: July 27, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share