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

NCT ID: NCT02106520

Last Updated: 2015-11-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2015-09-30

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

Conditions

Hereditary Hemorrhagic Telangiectasia; Epistaxis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Bevacizumab 25mg

Three administrations of 25 mg of Bevacizumab spaced of 14 days

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Bevacizumab 50mg

Three administrations of 50 mg of Bevacizumab spaced of 14 days

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Bevacizumab 75mg

Three administrations of 75 mg of Bevacizumab spaced of 14 days

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: DRUG

Placebo

Three administrations of placebo spaced of 14 days

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Interventions

Bevacizumab

Intervention Type: DRUG

placebo

Intervention Type: DRUG

Other Intervention Names

Three administrations of Bevacizumab spaced of 14 days; Three administrations of placebo spaced of 14 days

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sophie DUPUIS-GIROD, MD

Role: PRINCIPAL_INVESTIGATOR

Service de génétique, Hôpital Louis Pradel, Hospices Civils de Lyon

Locations

Hôpital Louis Pradel

Bron, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 27599328 (View on PubMed)

Other Identifiers

2013.827

Identifier Type: -

Identifier Source: org_study_id