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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon
ClinicalTrials.gov Identifier:
NCT01507480
First received: December 6, 2011
Last updated: May 13, 2013
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Hemorrhagic Hereditary Telangiectasia
Drug: Bevacizumab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The ELLIPSE Study: A Phase-1 Study Evaluating the Tolerance of Bevacizumab Nasal Spray to Treat Epistaxis in Hereditary Hemorrhagic Telangiectasia.

Resource links provided by NLM:


Further study details as provided by Hospices Civils de Lyon:

Primary Outcome Measures:
  • Tolerance [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    Evaluate the tolerance of increasing doses of bevacizumab administered as a nasal spray in patients with HHT-related epistaxis.


Secondary Outcome Measures:
  • Systemic passage and pharmacokinetics [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    Study the systemic passage and pharmacokinetics of bevacizumab in these patients.

  • Efficacy [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    Evaluate the efficacy of bevacizumab nasal spray on the appearance of epistaxis (number, frequency)

  • Efficacy [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    Evaluate the efficacy of bevacizumab nasal spray on hemoglobinema and ferritin

  • Efficacy [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    Evaluate the efficacy of bevacizumab nasal spray on the number of red blood cell transfusions


Enrollment: 42
Study Start Date: October 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab
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
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:
Other Name: AVASTIN

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01507480

Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
Principal Investigator: Frederic FAURE, MD Hospices Civils de Lyon
  More Information

Additional Information:
No publications provided by Hospices Civils de Lyon

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT01507480     History of Changes
Other Study ID Numbers: 2010-650
Study First Received: December 6, 2011
Last Updated: May 13, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Hospices Civils de Lyon:
Hemorrhagic Hereditary Telangiectasia (HHT)
Antiangiogenic therapies
Bevacizumab

Additional relevant MeSH terms:
Epistaxis
Telangiectasia, Hereditary Hemorrhagic
Telangiectasis
Nose Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Hemorrhage
Pathologic Processes
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Hemorrhagic Disorders
Hematologic Diseases
Vascular Malformations
Cardiovascular Abnormalities
Congenital Abnormalities
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014