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BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT). (BABH)

Primary Purpose

Rendu Osler Disease, Telangiectasia, Hereditary Hemorrhagic

Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Bevacizumab
sodium chloride 0.9%
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rendu Osler Disease focused on measuring Hereditary Hemorrhagic Telangiectasia (HHT), VEGF therapy, Bevacizumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 three Curaçao criteria) and / or with molecular biology confirmation.
  • Blood transfusions with the requirement for at least 4 units of blood in the 3-month period before study enrollment, related to epistaxis or digestive bleeding.

Exclusion Criteria:

  • Women who are pregnant or nursing (lactating), women of child-bearing potential without reliable contraception during the treatment and for at least 6 months after the last dose.
  • 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 study.
  • Active infection and/or fever>38°C
  • Participation in another clinical trial within 28 days prior to inclusion.
  • Hypersensitivity to the active substance or to any of the excipients.
  • Known hypersensitivity to products of Chinese hamster ovary cells (CHO) or other recombinant human or humanized antibodies.
  • Patients who have taken Avastin ® intravenously in the 6 months prior to inclusion.
  • Patients who have had a therapeutic endoscopy for gastrointestinal bleeding or ENT surgery for epistaxis will have to wait at least 3 months less after treatment to be included if bleeding persists.
  • Patients who had a surgery in the month prior inclusion or planned surgery within 6 months
  • Severe peripheral arterial disease with ulcerations
  • Unhealed wound
  • Thrombosis in the 6 months prior to inclusion
  • Anticoagulant treatment
  • Uncontrolled high blood pressure

Sites / Locations

  • CHU d'Angers
  • Hôpital Ambroise Paré
  • Hôpital Femme Mère Enfant
  • CHU de Montpellier Hôpital St Eloi

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Bevacizumab

Placebo

Arm Description

Intravenous infusion of Bevacizumab at a dose of 5 mg/kg

0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations

Outcomes

Primary Outcome Measures

number of red blood cell transfusions

Secondary Outcome Measures

hemoglobin
The relative evolution in hemoglobin level at 3 months after the beginning of the treatment is compared to the value measured at inclusion
hemoglobin
The relative evolution in hemoglobin level at 6 months after the beginning of the treatment is compared to the value measured at inclusion
epistaxis frequency
Comparison of an average over a 3-month period before and after the treatment.
duration of nosebleeds
Comparison of an average over a 3-month period before and after the treatment.
digestive vascular malformations
Comparison of digestive endoscopy before and after treatment if gastrointestinal bleeding have already externalized before treatment
quality of life (SF36).
Comparison of SF36 questionnaire before and after treatment.
quality of life (SF36).
Comparison of SF36 questionnaire before and after treatment.
severity epistaxis score (ESS).
Comparison of ESS questionnaire before and after treatment
severity epistaxis score (ESS).
Comparison of ESS questionnaire before and after treatment
To evaluate pharmacokinetics of bevacizumab dose
Description of bevacizumab serum concentrations over time, the relationship between bevacizumab concentrations and adverse events and clinical/biological endpoints
To evaluate pharmacokinetics of bevacizumab dose
Description of bevacizumab serum concentrations over time, the relationship between bevacizumab concentrations and adverse events and clinical/biological endpoints
adverse events
To assess the safety of bevacizumab.Tolerance will be evaluated by recording adverse events and by clinical examinations during the treatment period and the follow up period.

Full Information

First Posted
July 21, 2017
Last Updated
October 14, 2021
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT03227263
Brief Title
BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT).
Acronym
BABH
Official Title
BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT). A National, Multicenter Phase III Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Completed
Study Start Date
September 28, 2017 (Actual)
Primary Completion Date
May 15, 2020 (Actual)
Study Completion Date
May 15, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The recognized manifestations of HHT are all due to abnormalities of vascular structure. Epistaxis and digestive arteriovenous malformations may be responsible for severe hemorrhages in 5% of HHT patients, requiring repeated blood transfusions and are associated with high morbidity. There is currently no standard and efficient management of this severe symptom. It is also well known that HHT-associated hemorrhages have the greatest negative impact on quality of life among HHT patients, and is responsible for anemia, blood transfusions, hospitalizations, depressive syndrome and a high psycho-social impact. Since 2006, it has been suggested by animal models and then by clinical reports that anti-VEGF therapy may be useful to treat HHT. 4 case reports have been published on efficacy of intravenous bevacizumab, a humanized monoclonal antibody in HHT on severe hemorrhages. Intravenous bevacizumab has been used in a previous clinical trial to measure efficacy and tolerance of this drug in HHT patients with severe liver involvement. Furthermore, a reduction was observed in the duration of the nosebleeds after treatment and was encouraging to treat bleeding. We completed this study by a pharmacokinetic-pharmacodynamic (PK-PD) model in order to assess the individual concentration-effect relationship of bevacizumab. However, no randomized prospective study has been performed and published to evaluate the efficacy in this indication. A total of 24 patients will be randomized versus placebo in a multicenter phase III trial. The Avastin or placebo will be infused at 5mg/kg every 14 days with a total of 6 cures with a 3 months following period.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rendu Osler Disease, Telangiectasia, Hereditary Hemorrhagic
Keywords
Hereditary Hemorrhagic Telangiectasia (HHT), VEGF therapy, Bevacizumab

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bevacizumab
Arm Type
Experimental
Arm Description
Intravenous infusion of Bevacizumab at a dose of 5 mg/kg
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
Bevacizumab (Avastin®) concentrate at 25mg/mL is diluted at 5 mg/kg for infusion every 14 days for 6 consecutive administrations
Intervention Type
Drug
Intervention Name(s)
sodium chloride 0.9%
Intervention Description
0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations
Primary Outcome Measure Information:
Title
number of red blood cell transfusions
Time Frame
6 months
Secondary Outcome Measure Information:
Title
hemoglobin
Description
The relative evolution in hemoglobin level at 3 months after the beginning of the treatment is compared to the value measured at inclusion
Time Frame
3 months
Title
hemoglobin
Description
The relative evolution in hemoglobin level at 6 months after the beginning of the treatment is compared to the value measured at inclusion
Time Frame
6 months
Title
epistaxis frequency
Description
Comparison of an average over a 3-month period before and after the treatment.
Time Frame
3 months before treatment up to 6 months from the inclusion
Title
duration of nosebleeds
Description
Comparison of an average over a 3-month period before and after the treatment.
Time Frame
3 months before treatment up to 6 months from the inclusion
Title
digestive vascular malformations
Description
Comparison of digestive endoscopy before and after treatment if gastrointestinal bleeding have already externalized before treatment
Time Frame
6 months
Title
quality of life (SF36).
Description
Comparison of SF36 questionnaire before and after treatment.
Time Frame
3 months
Title
quality of life (SF36).
Description
Comparison of SF36 questionnaire before and after treatment.
Time Frame
6 months
Title
severity epistaxis score (ESS).
Description
Comparison of ESS questionnaire before and after treatment
Time Frame
3 months
Title
severity epistaxis score (ESS).
Description
Comparison of ESS questionnaire before and after treatment
Time Frame
6 months.
Title
To evaluate pharmacokinetics of bevacizumab dose
Description
Description of bevacizumab serum concentrations over time, the relationship between bevacizumab concentrations and adverse events and clinical/biological endpoints
Time Frame
Before each 6 infusions
Title
To evaluate pharmacokinetics of bevacizumab dose
Description
Description of bevacizumab serum concentrations over time, the relationship between bevacizumab concentrations and adverse events and clinical/biological endpoints
Time Frame
2 hours after the first treatment infusion
Title
adverse events
Description
To assess the safety of bevacizumab.Tolerance will be evaluated by recording adverse events and by clinical examinations during the treatment period and the follow up period.
Time Frame
up to 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 three Curaçao criteria) and / or with molecular biology confirmation. Blood transfusions with the requirement for at least 4 units of blood in the 3-month period before study enrollment, related to epistaxis or digestive bleeding. Exclusion Criteria: Women who are pregnant or nursing (lactating), women of child-bearing potential without reliable contraception during the treatment and for at least 6 months after the last dose. 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 study. Active infection and/or fever>38°C Participation in another clinical trial within 28 days prior to inclusion. Hypersensitivity to the active substance or to any of the excipients. Known hypersensitivity to products of Chinese hamster ovary cells (CHO) or other recombinant human or humanized antibodies. Patients who have taken Avastin ® intravenously in the 6 months prior to inclusion. Patients who have had a therapeutic endoscopy for gastrointestinal bleeding or ENT surgery for epistaxis will have to wait at least 3 months less after treatment to be included if bleeding persists. Patients who had a surgery in the month prior inclusion or planned surgery within 6 months Severe peripheral arterial disease with ulcerations Unhealed wound Thrombosis in the 6 months prior to inclusion Anticoagulant treatment Uncontrolled high blood pressure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
DUPUIS-GIROD, MD
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU d'Angers
City
Angers
Country
France
Facility Name
Hôpital Ambroise Paré
City
Boulogne Billancourt
Country
France
Facility Name
Hôpital Femme Mère Enfant
City
Bron
Country
France
Facility Name
CHU de Montpellier Hôpital St Eloi
City
Montpellier
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT).

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