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:
Hospices Civils de Lyon
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
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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:
Genetics Home Reference related topics:
capillary malformation-arteriovenous malformation syndrome
hereditary hemorrhagic telangiectasia
Parkes Weber syndrome
Drug Information available for:
Bevacizumab
U.S. FDA Resources
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 More Information
Additional Information:
No publications provided
| 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 May 21, 2013