Clinical trial NCT02106520: Efficacy of a Bevacizumab Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
Official title: Efficacy of a Bevacizumab Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Hereditary Hemorrhagic Telangiectasia
Epistaxis
Keywords: Epistaxis
Bevacizumab
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2014-04-08
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years.
* Patients who have given their free informed and signed consent.
* Patients affiliated to a social security scheme or similar.
* Patients monitored for clinically confirmed HHT (presence of at least 3 Curaçao criteria) and/or confirmed by molecular biology.
* Patients who have not undergone nasal surgery in the 3 months prior to inclusion.
* 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:

* Women who are pregnant or likely to become so in the course of the study.
* Patients not affiliated to a social security scheme.
* Patients who are protected adults under the terms of the law (French Public Health Code).
* Refusal to consent.
* Patients for whom the diagnosis of HHT has not been confirmed clinically and/or by molecular biology.
* Patients with an on-going infectious condition.
* Participation in another clinical trial within the 28 days prior to inclusion.
* Known hypersensitivity to the active ingredient or one of the excipients.
* Known hypersensitivity to products of Chinese hamster ovary cells (CHO) or other human or humanized recombinant antibodies.
* Patients who have incompletely filled in the nosebleed grids in the 3 months preceding the treatment.
* 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.
* Patients who have received Avastin® intravenously in the 6 months prior to inclusion.

Primary outcomes:
measure: mean duration of epistaxis
timeFrame: 3 months after treatment
Secondary outcomes:
measure: adverse events
timeFrame: before and 6 months after treatment
measure: mean monthly epistaxis duration
timeFrame: 6 months after the end of the treatment
measure: frequency and duration of epistaxis
timeFrame: 3 months and 6 months after the end of the treatment
measure: Quality of life
timeFrame: 3 months and 6 months aftert the end of the treatment
measure: Number of red blood cells transfusion
timeFrame: 3 months and 6 months after the end of the treatment
measure: Change in hemoglobinemia and serum ferritin
timeFrame: 1 month, 3 months and 6 months
measure: Kinetics of monthly epistaxis duration
timeFrame: 6 months
Other outcomes:
Locations:
city: Bron
country: France
facility: Hôpital Louis Pradel
Study officials:
affiliation: Service de génétique, Hôpital Louis Pradel, Hospices Civils de Lyon
name: Sophie DUPUIS-GIROD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dupuis-Girod S, Ambrun A, Decullier E, Fargeton AE, Roux A, Breant V, Colombet B, Riviere S, Cartier C, Lacombe P, Chinet T, Blivet S, Blondel JH, Gilbert-Dussardier B, Dufour X, Michel J, Harle JR, Dessi P, Faure F. Effect of Bevacizumab Nasal Spray on Epistaxis Duration in Hereditary Hemorrhagic Telangectasia: A Randomized Clinical Trial. JAMA. 2016 Sep 6;316(9):934-42. doi: 10.1001/jama.2016.11387.