Efficacy of a Bevacizumab Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
Overview
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Hospices Civils de Lyon
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- mean duration of epistaxis
Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Bevacizumab 25mg
Three administrations of 25 mg of Bevacizumab spaced of 14 days
Intervention: Bevacizumab (Drug)
Bevacizumab 50mg
Three administrations of 50 mg of Bevacizumab spaced of 14 days
Intervention: Bevacizumab (Drug)
Bevacizumab 75mg
Three administrations of 75 mg of Bevacizumab spaced of 14 days
Intervention: Bevacizumab (Drug)
Placebo
Three administrations of placebo spaced of 14 days
Intervention: placebo (Drug)
Outcomes
Primary Outcomes
mean duration of epistaxis
Time Frame: 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 Outcomes
- adverse events(before and 6 months after treatment)
- mean monthly epistaxis duration(6 months after the end of the treatment)
- frequency and duration of epistaxis(3 months and 6 months after the end of the treatment)
- Quality of life(3 months and 6 months aftert the end of the treatment)
- Number of red blood cells transfusion(3 months and 6 months after the end of the treatment)
- Change in hemoglobinemia and serum ferritin(1 month, 3 months and 6 months)
- Kinetics of monthly epistaxis duration(6 months)