The ELLIPSE Study: A Phase-1 Study Evaluating the Tolerance of Bevacizumab Nasal Spray to Treat Epistaxis in Hereditary Hemorrhagic Telangiectasia

NCT01507480 | Completed Phase 1 DMC

• 1 other identifier: 2010-650
• Study Type: interventional
• Target: 42
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Rendu Osler Disease; Telangiectasia, Hereditary Hemorrhagic

Keywords

Hereditary Hemorrhagic Telangiectasia (HHT); Antiangiogenic therapies; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• Tolerance

  Evaluate the tolerance of increasing doses of bevacizumab administered as a nasal spray in patients with HHT-related epistaxis.

  3 months

Secondary Outcomes (4)

• Systemic passage and pharmacokinetics

  3 months

• Efficacy

  3 months

• Efficacy

  3 months

• Efficacy

  3 months

Study Arms (1)

Bevacizumab

EXPERIMENTAL

This 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.

Drug: Bevacizumab

Interventions

Bevacizumab DRUG

There are five increasing doses of bevacizumab nasal spray (25mg/mL): 10 mg, 25 mg, 50 mg, 75, mg and 100 mg. Each test dose is a single dose divided into five fractions and administered into each nostril every 30 minutes for 2 hours:

Also known as: AVASTIN

Bevacizumab

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Related Publications (1)

• Dupuis-Girod S, Ambrun A, Decullier E, Samson G, Roux A, Fargeton AE, Rioufol C, Schwiertz V, Disant F, Chapuis F, Donazzolo Y, Paintaud G, Edery P, Faure F. ELLIPSE Study: a Phase 1 study evaluating the tolerance of bevacizumab nasal spray in the treatment of epistaxis in hereditary hemorrhagic telangiectasia. MAbs. 2014 May-Jun;6(3):794-9. doi: 10.4161/mabs.28025. Epub 2014 Jan 30.

  PMID: 24481211 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Telangiectasia, Hereditary Hemorrhagic

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Telangiectasis; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Malformations; Cardiovascular Abnormalities; 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

Study Officials

• Frederic FAURE, MD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2011
• First Posted: January 11, 2012
• Study Start: October 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: October 19, 2021

Record last verified: 2011-12