Back to resultsEfficacy of a Bevacizumab Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT) (ALEGORI)
Primary Purpose
Hereditary Hemorrhagic Telangiectasia, Epistaxis
Status
Terminated
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Bevacizumab
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hereditary Hemorrhagic Telangiectasia focused on measuring Epistaxis, Bevacizumab
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.
Sites / Locations
- Hôpital Louis Pradel
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Bevacizumab 25mg
Bevacizumab 50mg
Bevacizumab 75mg
Placebo
Arm Description
Three administrations of 25 mg of Bevacizumab spaced of 14 days
Three administrations of 50 mg of Bevacizumab spaced of 14 days
Three administrations of 75 mg of Bevacizumab spaced of 14 days
Three administrations of placebo spaced of 14 days
Outcomes
Primary Outcome Measures
mean duration of epistaxis
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 Outcome Measures
adverse events
Adverse events observed along a repeated administration of bevacizumab (nasal spray administration) : evaluation by epistaxis monitoring along the study and by a clinical exam before each treatment and 6 months after the end of the treatment.
mean monthly epistaxis duration
To evaluate the efficacy at 6 months after the end of the treatment on the duration of the nosebleeds for the dose retained versus placebo
frequency and duration of epistaxis
Evolution of the frequency and the mean monthly duration of epistaxis at 3 and 6 months for the dose retained
Quality of life
Evolution of the quality of life score (SF-36) between the inclusion, 3 months and 6 months after the end of the treatment
Number of red blood cells transfusion
Evolution of the number of red blood cells transfusion between the inclusion and 3 and 6 months after the end of the treatment.
Change in hemoglobinemia and serum ferritin
Evolution of hemoglobinemia and serum ferritin at inclusion,3 and 6 months after the end of the treatment for the retained dose
Kinetics of monthly epistaxis duration
To describe the nosebleed kinetics for the dose retained and the placebo throughout the study
Full Information
NCT ID
NCT02106520
First Posted
April 1, 2014
Last Updated
November 19, 2015
Sponsor
Hospices Civils de Lyon
1. Study Identification
Unique Protocol Identification Number
NCT02106520
Brief Title
Efficacy of a Bevacizumab Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
Acronym
ALEGORI
Official Title
Efficacy of a Bevacizumab Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2015
Overall Recruitment Status
Terminated
Why Stopped
DSMB's decision following the first step analysis
Study Start Date
April 2014 (undefined)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
September 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Hemorrhagic Telangiectasia, Epistaxis
Keywords
Epistaxis, Bevacizumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Bevacizumab 25mg
Arm Type
Experimental
Arm Description
Three administrations of 25 mg of Bevacizumab spaced of 14 days
Arm Title
Bevacizumab 50mg
Arm Type
Experimental
Arm Description
Three administrations of 50 mg of Bevacizumab spaced of 14 days
Arm Title
Bevacizumab 75mg
Arm Type
Experimental
Arm Description
Three administrations of 75 mg of Bevacizumab spaced of 14 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Three administrations of placebo spaced of 14 days
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Three administrations of Bevacizumab spaced of 14 days
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
Three administrations of placebo spaced of 14 days
Primary Outcome Measure Information:
Title
mean duration of epistaxis
Description
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).
Time Frame
3 months after treatment
Secondary Outcome Measure Information:
Title
adverse events
Description
Adverse events observed along a repeated administration of bevacizumab (nasal spray administration) : evaluation by epistaxis monitoring along the study and by a clinical exam before each treatment and 6 months after the end of the treatment.
Time Frame
before and 6 months after treatment
Title
mean monthly epistaxis duration
Description
To evaluate the efficacy at 6 months after the end of the treatment on the duration of the nosebleeds for the dose retained versus placebo
Time Frame
6 months after the end of the treatment
Title
frequency and duration of epistaxis
Description
Evolution of the frequency and the mean monthly duration of epistaxis at 3 and 6 months for the dose retained
Time Frame
3 months and 6 months after the end of the treatment
Title
Quality of life
Description
Evolution of the quality of life score (SF-36) between the inclusion, 3 months and 6 months after the end of the treatment
Time Frame
3 months and 6 months aftert the end of the treatment
Title
Number of red blood cells transfusion
Description
Evolution of the number of red blood cells transfusion between the inclusion and 3 and 6 months after the end of the treatment.
Time Frame
3 months and 6 months after the end of the treatment
Title
Change in hemoglobinemia and serum ferritin
Description
Evolution of hemoglobinemia and serum ferritin at inclusion,3 and 6 months after the end of the treatment for the retained dose
Time Frame
1 month, 3 months and 6 months
Title
Kinetics of monthly epistaxis duration
Description
To describe the nosebleed kinetics for the dose retained and the placebo throughout the study
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sophie DUPUIS-GIROD, MD
Organizational Affiliation
Service de génétique, Hôpital Louis Pradel, Hospices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Louis Pradel
City
Bron
ZIP/Postal Code
69677
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
27599328
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.
Results Reference
derived
Learn more about this trial
Efficacy of a Bevacizumab Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
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