Back to resultsThe ELLIPSE Study: A Phase-1 Study Evaluating the Tolerance of Bevacizumab Nasal Spray to Treat Epistaxis in Hereditary Hemorrhagic Telangiectasia (ELLIPSE)
Primary Purpose
Rendu Osler Disease, Telangiectasia, Hereditary Hemorrhagic
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Rendu Osler Disease focused on measuring Hereditary Hemorrhagic Telangiectasia (HHT), Antiangiogenic therapies, Bevacizumab
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Bevacizumab
Arm Description
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.
Outcomes
Primary Outcome Measures
Tolerance
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
Study the systemic passage and pharmacokinetics of bevacizumab in these patients.
Efficacy
Evaluate the efficacy of bevacizumab nasal spray on the appearance of epistaxis (number, frequency)
Efficacy
Evaluate the efficacy of bevacizumab nasal spray on hemoglobinema and ferritin
Efficacy
Evaluate the efficacy of bevacizumab nasal spray on the number of red blood cell transfusions
Full Information
NCT ID
NCT01507480
First Posted
December 6, 2011
Last Updated
October 14, 2021
Sponsor
Hospices Civils de Lyon
1. Study Identification
Unique Protocol Identification Number
NCT01507480
Brief Title
The ELLIPSE Study: A Phase-1 Study Evaluating the Tolerance of Bevacizumab Nasal Spray to Treat Epistaxis in Hereditary Hemorrhagic Telangiectasia
Acronym
ELLIPSE
Official Title
The ELLIPSE Study: A Phase-1 Study Evaluating the Tolerance of Bevacizumab Nasal Spray to Treat Epistaxis in Hereditary Hemorrhagic Telangiectasia.
Study Type
Interventional
2. Study Status
Record Verification Date
December 2011
Overall Recruitment Status
Completed
Study Start Date
October 2011 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rendu Osler Disease, Telangiectasia, Hereditary Hemorrhagic
Keywords
Hereditary Hemorrhagic Telangiectasia (HHT), Antiangiogenic therapies, Bevacizumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
ParticipantInvestigator
Allocation
N/A
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bevacizumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
AVASTIN
Intervention Description
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:
Primary Outcome Measure Information:
Title
Tolerance
Description
Evaluate the tolerance of increasing doses of bevacizumab administered as a nasal spray in patients with HHT-related epistaxis.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Systemic passage and pharmacokinetics
Description
Study the systemic passage and pharmacokinetics of bevacizumab in these patients.
Time Frame
3 months
Title
Efficacy
Description
Evaluate the efficacy of bevacizumab nasal spray on the appearance of epistaxis (number, frequency)
Time Frame
3 months
Title
Efficacy
Description
Evaluate the efficacy of bevacizumab nasal spray on hemoglobinema and ferritin
Time Frame
3 months
Title
Efficacy
Description
Evaluate the efficacy of bevacizumab nasal spray on the number of red blood cell transfusions
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frederic FAURE, MD
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
24481211
Citation
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.
Results Reference
derived
Links:
URL
http://www.rendu-osler.fr
Description
Related Info
Learn more about this trial
The ELLIPSE Study: A Phase-1 Study Evaluating the Tolerance of Bevacizumab Nasal Spray to Treat Epistaxis in Hereditary Hemorrhagic Telangiectasia
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