Efficacy of a Bevacizumab Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- mean duration of epistaxis
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Bevacizumab 25mg
Three administrations of 25 mg of Bevacizumab spaced of 14 days
干预措施: Bevacizumab (Drug)
Bevacizumab 50mg
Three administrations of 50 mg of Bevacizumab spaced of 14 days
干预措施: Bevacizumab (Drug)
Bevacizumab 75mg
Three administrations of 75 mg of Bevacizumab spaced of 14 days
干预措施: Bevacizumab (Drug)
Placebo
Three administrations of placebo spaced of 14 days
干预措施: placebo (Drug)
结局指标
主要结局
mean duration of epistaxis
时间窗: 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).
次要结局
- 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)