Antiangiogenic drugs, such as bevacizumab, are a new treatment strategy in Hereditary Hemorrhagic Telangiectasia (HHT). Its systemic administration in patients with HHT improves liver damage-related symptoms and epistaxis (cases reported and on-going study-ClinicalTrials.gov Identifier #NCT00843440-). To limit the systemic adverse effects of bevacizumab and to ease administration, a local administration seems suitable.

A clinical case recently showed the benefits of bevacizumab nasal spray in these patients. Its results were confirmed in a characterization study on bevacizumab transport through porcine nasal mucosa (in press).

It seems necessary to assess the tolerance and efficacy of bevacizumab nasal spray in humans for the treatment of epistaxis in HHT with a prospective phase 1 study.

The primary objective of the study is to evaluate the tolerance of increasing doses of bevacizumab administered as a nasal spray in patients with HHT-related epistaxis.

This phase-1, randomized, double-blind, placebo-controlled, monocentric study is to be carried out sequentially (dose escalation) on 5 groups of 8 patients. Each group is made up of 6 verum and 2 placebos.

Inclusion Criteria:

• Age ≥ 18 years.
• Patients who give voluntary, informed consent and sign a consent form.
• Patients affiliated with the French universal health care system.
• Patients treated for HHT, that has been confirmed clinically (presence of at lease 3 Curaçao criteria) and/or by molecular biology.
• Patients who fill out epistaxis tally sheets completely in the three months before inclusion.
• Patients who present severe epistaxis averaging over 30 minutes in the three months before inclusion ((duration M1 + duration M2 + duration M3) / 3).
• Patients whose number of red blood cell transfusions in the six months before inclusion is known.
• Patients who have not undergone nasal surgery in the three months before inclusion.

Exclusion Criteria:

• Pregnant women or women who could become pregnant during the study.
• Patients not affiliated with the French universal health care system.
• Patients who are protected adults according to the terms of the law (French public health laws).
• Refusal to give consent.
• Patients whose HHT diagnosis has not be confirmed clinically and/or by molecular biology.
• Infectious episode.
• Patients presenting unchecked hypertension at the time of inclusion (systolic BP > 150 mmHg and/or diastolic BP > 100 mmHg) with or without treatment. -Patients with hypertension can be included, once blood pressure levels have been controlled by appropriate medical treatment.
• Participation in another therapeutic trial in the 28 days before inclusion. Patients who have already being treated with bevacizumab by intravenous infusion.
• A known hypersensitivity to the active substance or one of its excipients.A known hypersensitivity to products containing Chinese hamster ovarian (CHO) cells or to other human or humanized recombinant antibodies.