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

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ClinicalTrials.gov Identifier: NCT02106520
Recruitment Status : Terminated (DSMB's decision following the first step analysis)
First Posted : April 8, 2014
Last Update Posted : November 20, 2015
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

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


Condition or disease Intervention/treatment Phase
Hereditary Hemorrhagic Telangiectasia Epistaxis Drug: Bevacizumab Drug: placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy of a Bevacizumab Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (HHT)
Study Start Date : April 2014
Actual Primary Completion Date : June 2015
Actual Study Completion Date : September 2015


Arm Intervention/treatment
Experimental: Bevacizumab 25mg
Three administrations of 25 mg of Bevacizumab spaced of 14 days
Drug: Bevacizumab
Other Name: Three administrations of Bevacizumab spaced of 14 days

Experimental: Bevacizumab 50mg
Three administrations of 50 mg of Bevacizumab spaced of 14 days
Drug: Bevacizumab
Other Name: Three administrations of Bevacizumab spaced of 14 days

Experimental: Bevacizumab 75mg
Three administrations of 75 mg of Bevacizumab spaced of 14 days
Drug: Bevacizumab
Other Name: Three administrations of Bevacizumab spaced of 14 days

Placebo Comparator: Placebo
Three administrations of placebo spaced of 14 days
Drug: placebo
Other Name: Three administrations of placebo spaced of 14 days




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. adverse events [ Time Frame: before and 6 months after treatment ]
    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.

  2. mean monthly epistaxis duration [ Time Frame: 6 months after the end of the treatment ]
    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

  3. frequency and duration of epistaxis [ Time Frame: 3 months and 6 months after the end of the treatment ]
    Evolution of the frequency and the mean monthly duration of epistaxis at 3 and 6 months for the dose retained

  4. Quality of life [ Time Frame: 3 months and 6 months aftert the end of the treatment ]
    Evolution of the quality of life score (SF-36) between the inclusion, 3 months and 6 months after the end of the treatment

  5. Number of red blood cells transfusion [ Time Frame: 3 months and 6 months after the end of the treatment ]
    Evolution of the number of red blood cells transfusion between the inclusion and 3 and 6 months after the end of the treatment.

  6. Change in hemoglobinemia and serum ferritin [ Time Frame: 1 month, 3 months and 6 months ]
    Evolution of hemoglobinemia and serum ferritin at inclusion,3 and 6 months after the end of the treatment for the retained dose

  7. Kinetics of monthly epistaxis duration [ Time Frame: 6 months ]
    To describe the nosebleed kinetics for the dose retained and the placebo throughout the study



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02106520


Locations
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France
Hôpital Louis Pradel
Bron, France, 69677
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
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Principal Investigator: Sophie DUPUIS-GIROD, MD Service de génétique, Hôpital Louis Pradel, Hospices Civils de Lyon

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT02106520     History of Changes
Other Study ID Numbers: 2013.827
First Posted: April 8, 2014    Key Record Dates
Last Update Posted: November 20, 2015
Last Verified: November 2015

Keywords provided by Hospices Civils de Lyon:
Epistaxis
Bevacizumab

Additional relevant MeSH terms:
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Telangiectasis
Epistaxis
Telangiectasia, Hereditary Hemorrhagic
Vascular Diseases
Cardiovascular Diseases
Nose Diseases
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Hemorrhage
Pathologic Processes
Signs and Symptoms, Respiratory
Signs and Symptoms
Hemostatic Disorders
Hemorrhagic Disorders
Hematologic Diseases
Vascular Malformations
Cardiovascular Abnormalities
Congenital Abnormalities
Bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors