ELLIPSE Study: a Phase 1 study evaluating the tolerance of bevacizumab nasal spray in the treatment of epistaxis in hereditary hemorrhagic telangiectasia.

Abstract

BACKGROUND:

Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited genetic vascular disorder in which epistaxis is the most frequent manifestation, responsible for high morbidity. Management of this symptom has no standard, and local treatments are often aggressive. Their efficacy is variable and has not been proven. Anti-angiogenic drugs, such as bevacizumab, are a new treatment strategy. Its systemic administration in patients with HHT improves liver damage-related symptoms and epistaxis. To limit the systemic adverse effects of bevacizumab and to ease administration, a local administration seems suitable.

PRIMARY OBJECTIVE:

To evaluate the tolerance of increasing doses of bevacizumab administered as a nasal spray in patients with HHT-related epistaxis. Secondary objectives were to study the bioavailability and efficacy of bevacizumab against epistaxis when given as a nasal spray.

METHODOLOGY:

Phase 1, randomized, double-blind, placebo-controlled, monocentric study performed sequentially (dose escalation) on 5 groups of 8 patients. Each group was made up of 6 verum and 2 placebos. Five increasing doses of bevacizumab nasal spray (25 mg/mL) were evaluated: 12.5, 25, 50, 75 and 100 mg.

RESULTS:

A total of 40 patients were included between October 2011 and October 2012. Bevacizumab nasal spray was well tolerated in all patients and the drug was not detected in their serum. No dose limiting toxicity was observed. No efficacy was observed at any dose in this study.

CONCLUSION:

Based on these results, bevacizumab nasal spray is a safe treatment of epistaxis in HHT. However, a randomized Phase 2 study is needed to determine its efficacy.

TRIAL REGISTRATION:

ClinicalTrials.gov Identifier #NCT01507480.

• Authors: Sophie Dupuis-Girod, Alexis Ambrun, Evelyne Decullier, Géraldine Samson, Adeline Roux, Anne-Emmanuelle Fargeton, Catherine Rioufol, Verane Schwiertz, François Disant, François Chapuis, Yves Donazzolo, Gilles Paintaud, Patrick Edery, Frederic Faure
• Journal: mAbs (MAbs) 2014 May-Jun Vol. 6 Issue 3 Pg. 794-9 ISSN: 1942-0870 [Electronic] United States
• PMID: 24481211 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal, Humanized
• Nasal Sprays
• Bevacizumab

Topics

• Adult
• Aged
• Angiogenesis Inhibitors (administration & dosage, adverse effects, pharmacokinetics)
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects, pharmacokinetics)
• Bevacizumab
• Blood Transfusion
• Dose-Response Relationship, Immunologic
• Double-Blind Method
• Epistaxis (etiology, therapy)
• Female
• Humans
• Male
• Middle Aged
• Nasal Sprays
• Telangiectasia, Hereditary Hemorrhagic (complications, therapy)
• Treatment Outcome