Efficacy of a Bevacizumab Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) (ALEGORI)

Civil Hospices of Lyon

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Hereditary Hemorrhagic Telangiectasia; Epistaxis

Treatments: Drug: placebo; Drug: Bevacizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT02106520

2013.827

Details and patient eligibility

About

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

Enrollment: 80 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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80 participants in 4 patient groups, including a placebo group

Bevacizumab 25mg

Experimental group

Description:

Three administrations of 25 mg of Bevacizumab spaced of 14 days

Treatment:

Drug: Bevacizumab

Bevacizumab 50mg

Experimental group

Description:

Three administrations of 50 mg of Bevacizumab spaced of 14 days

Treatment:

Drug: Bevacizumab

Bevacizumab 75mg

Experimental group

Description:

Three administrations of 75 mg of Bevacizumab spaced of 14 days

Treatment:

Drug: Bevacizumab

Placebo

Placebo Comparator group

Description:

Three administrations of placebo spaced of 14 days

Treatment:

Drug: placebo