<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03227263</url>
  </required_header>
  <id_info>
    <org_study_id>69HCL17_0018</org_study_id>
    <secondary_id>2017-001031-39</secondary_id>
    <nct_id>NCT03227263</nct_id>
  </id_info>
  <brief_title>BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT).</brief_title>
  <acronym>BABH</acronym>
  <official_title>BABH Study: Efficacy and Safety of Bevacizumab on Severe Bleedings Associated With Hemorrhagic Hereditary Telangiectasia (HHT). A National, Multicenter Phase III Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospices Civils de Lyon</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The recognized manifestations of HHT are all due to abnormalities of vascular structure.&#xD;
      Epistaxis and digestive arteriovenous malformations may be responsible for severe hemorrhages&#xD;
      in 5% of HHT patients, requiring repeated blood transfusions and are associated with high&#xD;
      morbidity. There is currently no standard and efficient management of this severe symptom. It&#xD;
      is also well known that HHT-associated hemorrhages have the greatest negative impact on&#xD;
      quality of life among HHT patients, and is responsible for anemia, blood transfusions,&#xD;
      hospitalizations, depressive syndrome and a high psycho-social impact.&#xD;
&#xD;
      Since 2006, it has been suggested by animal models and then by clinical reports that&#xD;
      anti-VEGF therapy may be useful to treat HHT. 4 case reports have been published on efficacy&#xD;
      of intravenous bevacizumab, a humanized monoclonal antibody in HHT on severe hemorrhages.&#xD;
&#xD;
      Intravenous bevacizumab has been used in a previous clinical trial to measure efficacy and&#xD;
      tolerance of this drug in HHT patients with severe liver involvement. Furthermore, a&#xD;
      reduction was observed in the duration of the nosebleeds after treatment and was encouraging&#xD;
      to treat bleeding. We completed this study by a pharmacokinetic-pharmacodynamic (PK-PD) model&#xD;
      in order to assess the individual concentration-effect relationship of bevacizumab.&#xD;
&#xD;
      However, no randomized prospective study has been performed and published to evaluate the&#xD;
      efficacy in this indication. A total of 24 patients will be randomized versus placebo in a&#xD;
      multicenter phase III trial. The Avastin or placebo will be infused at 5mg/kg every 14 days&#xD;
      with a total of 6 cures with a 3 months following period.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 28, 2017</start_date>
  <completion_date type="Actual">May 15, 2020</completion_date>
  <primary_completion_date type="Actual">May 15, 2020</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>number of red blood cell transfusions</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>hemoglobin</measure>
    <time_frame>3 months</time_frame>
    <description>The relative evolution in hemoglobin level at 3 months after the beginning of the treatment is compared to the value measured at inclusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>hemoglobin</measure>
    <time_frame>6 months</time_frame>
    <description>The relative evolution in hemoglobin level at 6 months after the beginning of the treatment is compared to the value measured at inclusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>epistaxis frequency</measure>
    <time_frame>3 months before treatment up to 6 months from the inclusion</time_frame>
    <description>Comparison of an average over a 3-month period before and after the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>duration of nosebleeds</measure>
    <time_frame>3 months before treatment up to 6 months from the inclusion</time_frame>
    <description>Comparison of an average over a 3-month period before and after the treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>digestive vascular malformations</measure>
    <time_frame>6 months</time_frame>
    <description>Comparison of digestive endoscopy before and after treatment if gastrointestinal bleeding have already externalized before treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>quality of life (SF36).</measure>
    <time_frame>3 months</time_frame>
    <description>Comparison of SF36 questionnaire before and after treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>quality of life (SF36).</measure>
    <time_frame>6 months</time_frame>
    <description>Comparison of SF36 questionnaire before and after treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>severity epistaxis score (ESS).</measure>
    <time_frame>3 months</time_frame>
    <description>Comparison of ESS questionnaire before and after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>severity epistaxis score (ESS).</measure>
    <time_frame>6 months.</time_frame>
    <description>Comparison of ESS questionnaire before and after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate pharmacokinetics of bevacizumab dose</measure>
    <time_frame>Before each 6 infusions</time_frame>
    <description>Description of bevacizumab serum concentrations over time, the relationship between bevacizumab concentrations and adverse events and clinical/biological endpoints</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate pharmacokinetics of bevacizumab dose</measure>
    <time_frame>2 hours after the first treatment infusion</time_frame>
    <description>Description of bevacizumab serum concentrations over time, the relationship between bevacizumab concentrations and adverse events and clinical/biological endpoints</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>adverse events</measure>
    <time_frame>up to 6 months</time_frame>
    <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.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Rendu Osler Disease</condition>
  <condition>Telangiectasia, Hereditary Hemorrhagic</condition>
  <arm_group>
    <arm_group_label>Bevacizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous infusion of Bevacizumab at a dose of 5 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>Bevacizumab (Avastin®) concentrate at 25mg/mL is diluted at 5 mg/kg for infusion every 14 days for 6 consecutive administrations</description>
    <arm_group_label>Bevacizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sodium chloride 0.9%</intervention_name>
    <description>0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  Patients who have given their free informed and signed consent.&#xD;
&#xD;
          -  Patients affiliated to a social security scheme or similar.&#xD;
&#xD;
          -  Patients monitored for clinically confirmed HHT (presence of at least three Curaçao&#xD;
             criteria) and / or with molecular biology confirmation.&#xD;
&#xD;
          -  Blood transfusions with the requirement for at least 4 units of blood in the 3-month&#xD;
             period before study enrollment, related to epistaxis or digestive bleeding.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are pregnant or nursing (lactating), women of child-bearing potential&#xD;
             without reliable contraception during the treatment and for at least 6 months after&#xD;
             the last dose.&#xD;
&#xD;
          -  Patients who are protected adults under the terms of the law (French Public Health&#xD;
             Code).&#xD;
&#xD;
          -  Refusal to consent.&#xD;
&#xD;
          -  Patients for whom the diagnosis of HHT has not been confirmed clinically and / or by&#xD;
             molecular biology study.&#xD;
&#xD;
          -  Active infection and/or fever&gt;38°C&#xD;
&#xD;
          -  Participation in another clinical trial within 28 days prior to inclusion.&#xD;
&#xD;
          -  Hypersensitivity to the active substance or to any of the excipients.&#xD;
&#xD;
          -  Known hypersensitivity to products of Chinese hamster ovary cells (CHO) or other&#xD;
             recombinant human or humanized antibodies.&#xD;
&#xD;
          -  Patients who have taken Avastin ® intravenously in the 6 months prior to inclusion.&#xD;
&#xD;
          -  Patients who have had a therapeutic endoscopy for gastrointestinal bleeding or ENT&#xD;
             surgery for epistaxis will have to wait at least 3 months less after treatment to be&#xD;
             included if bleeding persists.&#xD;
&#xD;
          -  Patients who had a surgery in the month prior inclusion or planned surgery within 6&#xD;
             months&#xD;
&#xD;
          -  Severe peripheral arterial disease with ulcerations&#xD;
&#xD;
          -  Unhealed wound&#xD;
&#xD;
          -  Thrombosis in the 6 months prior to inclusion&#xD;
&#xD;
          -  Anticoagulant treatment&#xD;
&#xD;
          -  Uncontrolled high blood pressure&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>DUPUIS-GIROD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospices Civils de Lyon</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU d'Angers</name>
      <address>
        <city>Angers</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Ambroise Paré</name>
      <address>
        <city>Boulogne Billancourt</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Femme Mère Enfant</name>
      <address>
        <city>Bron</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Montpellier Hôpital St Eloi</name>
      <address>
        <city>Montpellier</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>July 21, 2017</study_first_submitted>
  <study_first_submitted_qc>July 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2017</study_first_posted>
  <last_update_submitted>October 14, 2021</last_update_submitted>
  <last_update_submitted_qc>October 14, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hereditary Hemorrhagic Telangiectasia (HHT)</keyword>
  <keyword>VEGF therapy</keyword>
  <keyword>Bevacizumab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Telangiectasis</mesh_term>
    <mesh_term>Telangiectasia, Hereditary Hemorrhagic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03227263
org study id: 69HCL17_0018
secondary id: 2017-001031-39
nct id: NCT03227263
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: number of red blood cell transfusions
time frame: 6 months
measure: hemoglobin
time frame: 3 months
description: The relative evolution in hemoglobin level at 3 months after the beginning of the treatment is compared to the value measured at inclusion
measure: hemoglobin
time frame: 6 months
description: The relative evolution in hemoglobin level at 6 months after the beginning of the treatment is compared to the value measured at inclusion
measure: epistaxis frequency
time frame: 3 months before treatment up to 6 months from the inclusion
description: Comparison of an average over a 3-month period before and after the treatment.
measure: duration of nosebleeds
time frame: 3 months before treatment up to 6 months from the inclusion
description: Comparison of an average over a 3-month period before and after the treatment.
measure: digestive vascular malformations
time frame: 6 months
description: Comparison of digestive endoscopy before and after treatment if gastrointestinal bleeding have already externalized before treatment
measure: quality of life (SF36).
time frame: 3 months
description: Comparison of SF36 questionnaire before and after treatment.
measure: quality of life (SF36).
time frame: 6 months
description: Comparison of SF36 questionnaire before and after treatment.
measure: severity epistaxis score (ESS).
time frame: 3 months
description: Comparison of ESS questionnaire before and after treatment
measure: severity epistaxis score (ESS).
time frame: 6 months.
description: Comparison of ESS questionnaire before and after treatment
measure: To evaluate pharmacokinetics of bevacizumab dose
time frame: Before each 6 infusions
description: Description of bevacizumab serum concentrations over time, the relationship between bevacizumab concentrations and adverse events and clinical/biological endpoints
measure: To evaluate pharmacokinetics of bevacizumab dose
time frame: 2 hours after the first treatment infusion
description: Description of bevacizumab serum concentrations over time, the relationship between bevacizumab concentrations and adverse events and clinical/biological endpoints
measure: adverse events
time frame: up to 6 months
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.
arm group label: Bevacizumab
arm group type: Experimental
description: Intravenous infusion of Bevacizumab at a dose of 5 mg/kg
arm group label: Placebo
arm group type: Placebo Comparator
description: 0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations
intervention type: Drug
intervention name: Bevacizumab
description: Bevacizumab (Avastin®) concentrate at 25mg/mL is diluted at 5 mg/kg for infusion every 14 days for 6 consecutive administrations
arm group label: Bevacizumab
intervention type: Drug
intervention name: sodium chloride 0.9%
description: 0.9% of sodium chloride is infused every 14 days for 6 consecutive administrations
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: DUPUIS-GIROD, MD
role: Principal Investigator
affiliation: Hospices Civils de Lyon
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Telangiectasis
mesh term: Telangiectasia, Hereditary Hemorrhagic
mesh term: Bevacizumab
sharing ipd: No