Efficacy and Safety of Anti-angiogenic Therapy With IV Bevacizumab in Patients With Symptomatic Cerebral Arteriovenous Malformations

NCT06264531 | Recruiting Phase 2 DMC

• 1 other identifier: JDS_2023_12
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Brain arteriovenous malformations (AVMs) are responsible for hemorrhagic strokes, particularly in children and young adults. They can also be responsible for chronic neurological disorders: motor or sensory deficits, disturbances of higher functions, epilepsy or disabling headaches. The management of brain AVMs is complex and requires a multidisciplinary approach in an expert center. Available therapies include endovascular embolization, neurosurgical resection and/or radiosurgery. These procedures carry a risk of neurological complications, and are reserved for small AVMs located at a distance from highly functional cerebral structures. To date, no drug therapy is recommended if interventional treatment is not possible. Several studies on resected brain AVM tissue have demonstrated that these malformations are the site of significant evolutionary inflammatory and neo-angiogenesis processes. Other studies have specifically shown that VEGF (vascular endothelial growth factor) levels are increased in AVMs. More recently, a pre-clinical study showed that anti-angiogenic treatment with Bevacizumab reduced vascular proliferation within AVMs in mice. Finally, a Phase II clinical trial in patients with Rendu-Osler disease (a genetic vascular disorder characterized by recurrent epistaxis, cutaneous telangiectasia and the presence of visceral AVMs) showed a clinical benefit of IV Bevacizumab on the symptomatology of these vascular malformations, with a reduction in the risk of hemorrhage and the extent of hepatic arteriovenous shunts. A randomized Phase III trial is currently underway (NCT03227263) to assess the efficacy of IV Bevacizumab in Rendu-Osler disease. The aim of our study is to assess the efficacy of IV Bevacizumab on the disabling symptoms associated with symptomatic brain AVMs.

Conditions

Cerebral AV Malformation

Outcome Measures

Primary Outcomes (1)

• Proportion of patients showing at least one of the following improvements : cognition, neurological symptoms, epilepsy symptoms, headaches.

  Proportion of patients showing at least one of the following improvements : * change of at least 5 points in Montreal Cognitive Assessment score (from 0 to 30 ; higher score meaning a better outcome) * change of at least 4 points in National Institutes of Health Stroke Scale ( from 0 to 42 : higher score meaning a worse outcome) * change of at least one stage on the Epilepsy Balance Score (from 1 to 5 ; higher score meaning a worse outcome) * change of at least 12 points on the Headache ImpactTest-6 score (from 36 to 78 : higher score meaning a worse outcome)

  month 6

Study Arms (2)

bevacizumab

EXPERIMENTAL

Bevacizumab 5 mg/kg as a slow infusion over 90 minutes every 14 days for a total of 6 injections

Drug: Bevacizumab

placebo

PLACEBO COMPARATOR

NaCl 0.9% as a slow infusion over 90 minutes every 14 days for a total of 6 injections

Drug: Placebo

Interventions

Bevacizumab DRUG

Bevacizumab 5 mg/kg as a slow infusion over 90 minutes every 14 days for a total of 6 injections

bevacizumab

Placebo DRUG

NaCl 0.9% slow infusion over 90 minutes every 14 days for a total of 6 injections

placebo

Eligibility Criteria

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

You may qualify if:

• Patient over 18 years of age
• With a symptomatic cerebral AVM (chronic headache, focal neurological deficit, cognitive impairment, epilepsy) of Spetzler and Martin grade III, IV or V.
• Whose symptoms are sufficiently severe to allow significant improvement with treatment:
• MoCA score ≤ 25 and/or
• NIHSS score ≥ 4 and/or
• Epilepsy Balance Score ≥ 2 and/or
• HIT-6 score ≥ 48
• With functional signs and symptoms not sequellar to a previous bleeding episode AND disabling (mRS\>1)
• Ineligible for therapeutic intervention (endovascular or neurosurgery or radiosurgery)
• With normal bone marrow, liver and kidney function
• Having received informed consent to participate in the study
• Affiliated or beneficiary of a social security scheme

You may not qualify if:

• Known allergy to bevacizumab or an excipient.
• Hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanized antibodies.
• Contraindication to cerebral MRI
• Absolute or relative contraindication to gadolinium injection
• Proteinuria ≥ 2+ on urine dipstick (patients with proteinuria ≥2+ on urine dipstick will need to have proteinuria ≤ 1g protein on 24-hour urine to be eligible)
• Uncontrolled hypertension (PAS \>150 and/or PAD \> 100 mmHg)
• History of hypertensive crisis or hypertensive encephalopathy
• Congestive heart failure (New York Heart Association Grade II or higher)
• Previous myocardial infarction or unstable angina in the preceding 12 months
• Symptomatic peripheral vascular disease
• Vascular disease (aortic aneurysm, aortic dissection)
• Significant unhealed wound, ulcer or bone fracture
• Atrial fibrillation
• Patient under legal protection
• Pregnant or breast-feeding women

Sponsors & Collaborators

• Fondation Ophtalmologique Adolphe de Rothschild: lead

Study Sites (1)

HFAR

Paris, Île-de-France Region, 75019, France

RECRUITING

MeSH Terms

Conditions

Intracranial Arteriovenous Malformations

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Central Nervous System Vascular Malformations; Nervous System Malformations; Arteriovenous Malformations; Vascular Malformations; Cardiovascular Abnormalities; Cardiovascular Diseases; Vascular Diseases; Intracranial Arterial Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Jean-Philippe Désilles, MD, PhD

CONTACT

01 48 03 64 54; jpdesilles@for.paris

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2024
• First Posted: February 20, 2024
• Study Start: January 16, 2026
• Primary Completion (Estimated): January 15, 2028
• Study Completion (Estimated): January 15, 2029
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)