ALEGORI: Efficacy of a Bevacizumab Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
Study Details
Study Description
Brief Summary
Hereditary Hemorrhagic Telangiectasia (HHT) is a rare (~ 1/6000) but ubiquitous genetic disease. It is associated with abnormal angiogenesis and autosomal dominant inheritance, leading to telangiectasias and arteriovenous fistulae. More than 95% of patients are concerned by epistaxis (nosebleeds). These events are spontaneous, repeated, irregular, both diurnal and nocturnal, a source of anemia, disabling and very socially embarrassing.
Anti-angiogenic treatments, including bevacizumab, are a new therapeutic option in HHT.
The aim of this study is to evaluate 3 months after the end of the treatment the efficacy on the duration of the nosebleeds with 3 different doses (25, 50 and 75 mg) of bevacizumab administered as a nasal spray in a repeated manner (3 administrations) in patients with Hereditary Hemorrhagic Telangiectasia complicated by nosebleeds.
This randomized, double-blind, placebo-controlled, seamless phase II/III study is to be carried out on 4 groups of 20 patients for first step and 2 groups of 20 to 40 patients for second step
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2/Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Bevacizumab 25mg Three administrations of 25 mg of Bevacizumab spaced of 14 days |
Drug: Bevacizumab
Other Names:
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Experimental: Bevacizumab 50mg Three administrations of 50 mg of Bevacizumab spaced of 14 days |
Drug: Bevacizumab
Other Names:
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Experimental: Bevacizumab 75mg Three administrations of 75 mg of Bevacizumab spaced of 14 days |
Drug: Bevacizumab
Other Names:
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Placebo Comparator: Placebo Three administrations of placebo spaced of 14 days |
Drug: placebo
Other Names:
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Outcome Measures
Primary Outcome Measures
- mean duration of epistaxis [3 months after treatment]
To evaluate 3 months after the end of the treatment the efficacy on the duration of the nosebleeds with 3 different doses (25, 50 and 75 mg) of bevacizumab administered as a nasal spray in a repeated manner (3 administrations).
Secondary Outcome Measures
- adverse events [before and 6 months after treatment]
Adverse events observed along a repeated administration of bevacizumab (nasal spray administration) : evaluation by epistaxis monitoring along the study and by a clinical exam before each treatment and 6 months after the end of the treatment.
- mean monthly epistaxis duration [6 months after the end of the treatment]
To evaluate the efficacy at 6 months after the end of the treatment on the duration of the nosebleeds for the dose retained versus placebo
- frequency and duration of epistaxis [3 months and 6 months after the end of the treatment]
Evolution of the frequency and the mean monthly duration of epistaxis at 3 and 6 months for the dose retained
- Quality of life [3 months and 6 months aftert the end of the treatment]
Evolution of the quality of life score (SF-36) between the inclusion, 3 months and 6 months after the end of the treatment
- Number of red blood cells transfusion [3 months and 6 months after the end of the treatment]
Evolution of the number of red blood cells transfusion between the inclusion and 3 and 6 months after the end of the treatment.
- Change in hemoglobinemia and serum ferritin [1 month, 3 months and 6 months]
Evolution of hemoglobinemia and serum ferritin at inclusion,3 and 6 months after the end of the treatment for the retained dose
- Kinetics of monthly epistaxis duration [6 months]
To describe the nosebleed kinetics for the dose retained and the placebo throughout the study
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 18 years.
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Patients who have given their free informed and signed consent.
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Patients affiliated to a social security scheme or similar.
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Patients monitored for clinically confirmed HHT (presence of at least 3 Curaçao criteria) and/or confirmed by molecular biology.
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Patients who have not undergone nasal surgery in the 3 months prior to inclusion.
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Patient with nosebleeds of a monthly duration of more than 20 minutes and justified by follow-up grids completed for at least the 3 months prior to the time of inclusion.
Exclusion Criteria:
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Women who are pregnant or likely to become so in the course of the study.
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Patients not affiliated to a social security scheme.
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Patients who are protected adults under the terms of the law (French Public Health Code).
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Refusal to consent.
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Patients for whom the diagnosis of HHT has not been confirmed clinically and/or by molecular biology.
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Patients with an on-going infectious condition.
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Participation in another clinical trial within the 28 days prior to inclusion.
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Known hypersensitivity to the active ingredient or one of the excipients.
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Known hypersensitivity to products of Chinese hamster ovary cells (CHO) or other human or humanized recombinant antibodies.
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Patients who have incompletely filled in the nosebleed grids in the 3 months preceding the treatment.
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Patients who do not present with nosebleeds with a monthly average duration over the 3 months preceding the treatment of more than 20 minutes ((duration M1 + duration M2 + duration M3) / 3). Remark: only the 3 months strictly preceding the treatment will be taken into account, even if the grids have been completed over a longer period.
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Patients who have received Avastin® intravenously in the 6 months prior to inclusion.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Hôpital Louis Pradel | Bron | France | 69677 |
Sponsors and Collaborators
- Hospices Civils de Lyon
Investigators
- Principal Investigator: Sophie DUPUIS-GIROD, MD, Service de génétique, Hôpital Louis Pradel, Hospices Civils de Lyon
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2013.827