Hereditary Hemorrhagic TelangiectasiaPhase 2/3ALEGORINCT02106520
Efficacy of a Bevacizumab Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
A Phase 2/3 study testing Bevacizumab in people with Hereditary Hemorrhagic Telangiectasia and Epistaxis, run by Hospices Civils de Lyon at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hereditary Hemorrhagic Telangiectasia, Epistaxis
- What is being tested?
- Bevacizumab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2014to Sep 2015
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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 locations and contacts
1 site in 1 country.
About this study
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.
Read more
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
- Being tested
- Bevacizumab, placebo
- Keywords
- Epistaxis, Bevacizumab
- Medical subject headings
- Telangiectasia, Hereditary Hemorrhagic, Epistaxis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Three administrations of Bevacizumab spaced of 14 days
placeboDrug
Also called Three administrations of placebo spaced of 14 days
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab 25mg | Experimental | Three administrations of 25 mg of Bevacizumab spaced of 14 days Receives: Drug: Bevacizumab |
| Bevacizumab 50mg | Experimental | Three administrations of 50 mg of Bevacizumab spaced of 14 days Receives: Drug: Bevacizumab |
| Bevacizumab 75mg | Experimental | Three administrations of 75 mg of Bevacizumab spaced of 14 days Receives: Drug: Bevacizumab |
| Placebo | Placebo comparator | Three administrations of placebo spaced of 14 days Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 3 months after treatment
Secondary outcomes (7)
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.
Measured: before and 6 months after 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
Measured: 6 months after the end of the treatment
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
Measured: 3 months and 6 months after the end of the treatment
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
Measured: 3 months and 6 months aftert 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.
Measured: 3 months 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
Measured: 1 month, 3 months and 6 months
Kinetics of monthly epistaxis duration
To describe the nosebleed kinetics for the dose retained and the placebo throughout the study
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2014 (estimated)
- Study startApr 2014
- Primary completionJun 2015
- Study completionSep 2015
Why it stopped: DSMB's decision following the first step analysis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary Hemorrhagic TelangiectasiaStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sophie DUPUIS-GIROD, MD, Principal investigator, Service de génétique, Hôpital Louis Pradel, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02106520
- Sponsor's protocol ID
- 2013.827
- Acronym
- ALEGORI
- Status last verified
- Nov 2015
- First submitted
- 1 Apr 2014
- Last updated
- 20 Nov 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 27599328
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of a Bevacizumab Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
- ClinicalTrials.gov ID
- NCT02106520
- Acronym / sponsor ID
- ALEGORI / 2013.827
- Conditions
- Hereditary Hemorrhagic Telangiectasia, Epistaxis
- Keywords
- Epistaxis, Bevacizumab
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: DSMB's decision following the first step analysis
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- Jun 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 8 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab 25mg | Experimental | Drug: BevacizumabThree administrations of 25 mg of Bevacizumab spaced of 14 days |
| Bevacizumab 50mg | Experimental | Drug: BevacizumabThree administrations of 50 mg of Bevacizumab spaced of 14 days |
| Bevacizumab 75mg | Experimental | Drug: BevacizumabThree administrations of 75 mg of Bevacizumab spaced of 14 days |
| Placebo | Placebo comparator | Drug: placeboThree administrations of placebo spaced of 14 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BevacizumabAlso: Three administrations of Bevacizumab spaced of 14 days | Drug | Bevacizumab 25mg, Bevacizumab 50mg, Bevacizumab 75mg |
| placeboAlso: Three administrations of placebo spaced of 14 days | Drug | Placebo |
Primary outcome
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).
7 secondary outcomes
adverse events
Time frame: before and 6 months after treatment
mean monthly epistaxis duration
Time frame: 6 months after the end of the treatment
frequency and duration of epistaxis
Time frame: 3 months and 6 months after the end of the treatment
Quality of life
Time frame: 3 months and 6 months aftert the end of the treatment
Number of red blood cells transfusion
Time frame: 3 months and 6 months after the end of the treatment
Change in hemoglobinemia and serum ferritin
Time frame: 1 month, 3 months and 6 months
Kinetics of monthly epistaxis duration
Time frame: 6 months
Results and safety
The study was stopped early (reason given: DSMB's decision following the first step analysis). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2015.
- Derived from this study: PubMed 27599328Dupuis-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sophie DUPUIS-GIROD, MD principal investigator
Service de génétique, Hôpital Louis Pradel, Hospices Civils de Lyon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Bevacizumab in people with Hereditary Hemorrhagic Telangiectasia and Epistaxis, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: DSMB's decision following the first step analysis). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mean duration of epistaxis (time frame: 3 months after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02106520, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2015.