<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/NCT03010436</url>
  </required_header>
  <id_info>
    <org_study_id>HS-3010</org_study_id>
    <nct_id>NCT03010436</nct_id>
  </id_info>
  <brief_title>Benralizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis (EGPA) Study</brief_title>
  <acronym>BITE</acronym>
  <official_title>The Efficacy and Safety of Benralizumab In the Treatment of Eosinophilic Grandulomatosis With Polyangiitis (EGPA) Study: BITE</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Jewish Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National Jewish Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Benralizumab is a type of medicine called a monoclonal antibody that is made in the research&#xD;
      clinic; it works by blocking a specific protein in the body called interleukin-5. The study&#xD;
      medicine, benralizumab, is not yet approved for doctors to treat patients with EGPA. It is&#xD;
      considered an experimental drug in this study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is open-label which means that all subjects will receive the study medication. The&#xD;
      medicine-benralizumab-will be given to subjects in addition to the medicines they are already&#xD;
      taking to treat their EGPA such as oral steroids (e.g. prednisone) and medicines that reduce&#xD;
      the activity of their immune system. Drugs that are sometimes used (i.e., standard of care)&#xD;
      to reduce the activity of the immune system in EGPA (in addition to oral steroids) include&#xD;
      azathioprine, methotrexate, mycophenolate mofetil and cyclophosphamide. Information about how&#xD;
      the stud drug that you get affects the subjects body and their health will be collected&#xD;
      through a number of tests, procedures and questions.&#xD;
&#xD;
      The study medicine, benralizumab, will be given to subjects as one injection 30 mg under skin&#xD;
      every four weeks for 12 weeks and then every 8 weeks for 16 weeks for a total of 5&#xD;
      treatments. During the treatment phase of this study, a study staff member will call the&#xD;
      subjects to see how they are doing, what medications they are taking and if they are able to&#xD;
      decrease their steroid use. The study is a total of 9 study visits in a 44 week time period.&#xD;
      Everyone who takes part in the study will continue to receive his/her existing treatments for&#xD;
      EGPA (although their dose of oral steroids may be reduced during the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">April 15, 2017</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Actual">July 25, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>All adverse events will be reported by count of events (safety and tolerability )</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>All adverse events will be reported to AstraZeneca and the IRB in accordance with the policy of National Jewish Health and the FDA. Serious adverse events, whether or not considered related to the investigational drug, will be recorded on the SAE event form will be sent to AstraZeneca within 24 hours of submission to the FDA.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in corticosteroid dosage</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Change in steroid dose will be assessed by comparing the corticosteroid dose to subjects at the end of the steroid stable phase and compare to steroid dose at the end of treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the rate of EGPA exacerbations during the study period.</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Change in the rate of exacerbations will be assessed by comparing the rate of exacerbations during the study period with the rate during the washout and safety-monitoring period as well as with the self-reported rate of exacerbations from the year prior to the study.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Open-Label</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All subjects will receive the study medication- benralizumab</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Benralizumab</intervention_name>
    <description>one injection 30 mg under the subjects skin every 4 weeks for 8 weeks and then every 8 weeks for 24 weeks for a total of 5 treatments.</description>
    <arm_group_label>Open-Label</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed Consent: Able to give written informed consent prior to participation in the&#xD;
             study, which will include the ability to comply with the requirements and restrictions&#xD;
             listed in the consent form. Subjects must be able to read, comprehend, and write at a&#xD;
             level sufficient to complete study related materials.&#xD;
&#xD;
          -  Gender and Age: Male or female subjects &gt;18 years old&#xD;
&#xD;
          -  EGPA diagnosis: subjects who have been diagnosed with EGPA for at least 6 months based&#xD;
             on the history or presence of: asthma plus eosinophilia (&gt;1.0x109/L and/or &gt;10% of&#xD;
             leucocytes) plus at least two of the following additional features of EGPA&#xD;
&#xD;
               1. A biopsy showing histopathological evidence of eosinophilic vasculitis, or&#xD;
                  perivascular eosinophilic infiltration, or eosinophil-rich granulomatous&#xD;
                  inflammation;&#xD;
&#xD;
               2. Neuropathy, mono or poly (motor deficit or nerve conduction abnormality);&#xD;
&#xD;
               3. Pulmonary infiltrates, non-fixed;&#xD;
&#xD;
               4. Sino-nasal abnormality;&#xD;
&#xD;
               5. Cardiomyopathy (established by echocardiography or MRI);&#xD;
&#xD;
               6. Glomerulonephritis (haematuria, red cell casts, proteinuria);&#xD;
&#xD;
               7. Alveolar haemorrhage (by bronchoalveolar lavage);&#xD;
&#xD;
               8. Palpable purpura;&#xD;
&#xD;
               9. ANCA positive (MPO or PR3).&#xD;
&#xD;
          -  Subjects who have received cyclophosphamide can be included after a 4-week washout&#xD;
             prior to visit 0 (first injection).&#xD;
&#xD;
          -  Subjects who have received a methotrexate, azathioprine, or mycophenolate mofetil&#xD;
             induction regimen may be included if on a stable dose for at least 4 weeks prior to&#xD;
             visit 0.&#xD;
&#xD;
          -  Corticosteroid therapy: Subject must be on a stable dose of oral prednisolone or&#xD;
             prednisone of ≥5 mg/day for at least 4 weeks prior to visit 0.&#xD;
&#xD;
          -  Immunosuppressive therapy: If receiving immunosuppressive therapy (including&#xD;
             methotrexate, azathioprine, or mycophenolate mofetil, but excluding restricted&#xD;
             medications below) the dosage must be stable for the 4 weeks prior to visit 0 and&#xD;
             during the study (dose reductions for safety reasons will be permitted).&#xD;
&#xD;
          -  Female subjects: Women of childbearing potential (WOCBP) must use an effective form of&#xD;
             birth control (confirmed by the Investigator). Effective forms of birth control&#xD;
             include: true sexual abstinence, a vasectomized sexual partner, Implanon, female&#xD;
             sterilization by tubal occlusion, any effective IUD intrauterine device/IUS&#xD;
             levonogestrel Intrauterine system, Depo-Provera(tm) injections, oral contraceptive,&#xD;
             and Evra Patch(tm) or Nuvaring(tm). WOCBP must agree to use effective method of birth&#xD;
             control, as defined above, from enrolment, throughout the study duration and within 16&#xD;
             weeks after last dose of IP, and have negative serum pregnancy test result on Visit 0.&#xD;
&#xD;
          -  Women not of childbearing potential are defined as women who are either permanently&#xD;
             sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who&#xD;
             are postmenopausal. Women will be considered postmenopausal if they have been&#xD;
             amenorrheic for 12 months prior to the planned date of visit -1 without an alternative&#xD;
             medical cause. The following age-specific requirements apply:&#xD;
&#xD;
          -  Women &lt;50 years old would be considered postmenopausal if they have been amenorrheic&#xD;
             for 12 months or more following cessation of exogenous hormonal treatment and follicle&#xD;
             stimulating hormone (FSH) levels in the postmenopausal range.&#xD;
&#xD;
          -  Women ≥50 years old would be considered postmenopausal if they have been amenorrheic&#xD;
             for 12 months or more following cessation of all exogenous hormonal treatment.&#xD;
&#xD;
          -  All male subjects who are sexually active must agree to use an acceptable method of&#xD;
             contraception (condom with or without spermicide, vasectomy) from Visit 0 until 16&#xD;
             weeks after their last dose.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hypereosinophilic Syndrome&#xD;
&#xD;
          -  Wegener's Granulomatosis&#xD;
&#xD;
          -  History of cancer: Subjects who have had basal cell carcinoma, localized squamous cell&#xD;
             carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that&#xD;
             the subject is in remission and curative therapy was completed at least 12 months&#xD;
             prior to the date informed consent, and assent when applicable was obtained. Subjects&#xD;
             who have had other malignancies are eligible provided that the subject is in remission&#xD;
             and curative therapy was completed at least 5 years prior to the date informed&#xD;
             consent, and assent when applicable, was obtained.&#xD;
&#xD;
          -  A helminth parasitic infection diagnosed within 24 weeks prior to the date informed&#xD;
             consent is obtained that has not been treated with, or has failed to respond to&#xD;
             standard of care therapy.&#xD;
&#xD;
          -  Pregnant or nursing&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.5 times&#xD;
             the upper limit of normal (ULN) confirmed during screening period.&#xD;
&#xD;
          -  If female and of child-bearing potential, must have negative pregnancy test and must&#xD;
             adhere to acceptable method of contraception (with &lt;1% failure rate) during the study&#xD;
             and for four months after the study.&#xD;
&#xD;
          -  Receipt of any investigational non biologic within 30 days or 5 half-lives prior to&#xD;
             visit 0, whichever is longer.&#xD;
&#xD;
          -  A history of known immunodeficiency disorder including a positive human&#xD;
             immunodeficiency virus (HIV) test.&#xD;
&#xD;
          -  Any other medical illness that precludes study involvement&#xD;
&#xD;
          -  Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a&#xD;
             positive medical history for hepatitis B or C. Subjects with a history of hepatitis B&#xD;
             vaccination without history of hepatitis B are allowed to be enrolled.&#xD;
&#xD;
          -  Patients who are currently receiving or have previously received benralizumab or any&#xD;
             other type of anti-interleukin therapy (i.e. mepolizumab, reslizumab, lebrikizumab&#xD;
             etc.) within the last 4 months or 5 half-lives whichever is longer.&#xD;
&#xD;
          -  History of anaphylaxis to any biologic therapy or vaccine.&#xD;
&#xD;
          -  Receipt of immunoglobulin or blood products within 30 days prior to the date informed&#xD;
             consent is obtained.&#xD;
&#xD;
          -  Taking cyclophosphamide&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Wechsler, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Jewish Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Jewish Health</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>December 11, 2016</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>March 4, 2021</last_update_submitted>
  <last_update_submitted_qc>March 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Jewish Health</investigator_affiliation>
    <investigator_full_name>Michael Wechsler, MD</investigator_full_name>
    <investigator_title>Prinicipal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Systemic Vasculitis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Benralizumab</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/NCT03010436
org study id: HS-3010
nct id: NCT03010436
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Benralizumab is a type of medicine called a monoclonal antibody that is made in the research
      clinic; it works by blocking a specific protein in the body called interleukin-5. The study
      medicine, benralizumab, is not yet approved for doctors to treat patients with EGPA. It is
      considered an experimental drug in this study.
This study is open-label which means that all subjects will receive the study medication. The
      medicine-benralizumab-will be given to subjects in addition to the medicines they are already
      taking to treat their EGPA such as oral steroids (e.g. prednisone) and medicines that reduce
      the activity of their immune system. Drugs that are sometimes used (i.e., standard of care)
      to reduce the activity of the immune system in EGPA (in addition to oral steroids) include
      azathioprine, methotrexate, mycophenolate mofetil and cyclophosphamide. Information about how
      the stud drug that you get affects the subjects body and their health will be collected
      through a number of tests, procedures and questions.

      The study medicine, benralizumab, will be given to subjects as one injection 30 mg under skin
      every four weeks for 12 weeks and then every 8 weeks for 16 weeks for a total of 5
      treatments. During the treatment phase of this study, a study staff member will call the
      subjects to see how they are doing, what medications they are taking and if they are able to
      decrease their steroid use. The study is a total of 9 study visits in a 44 week time period.
      Everyone who takes part in the study will continue to receive his/her existing treatments for
      EGPA (although their dose of oral steroids may be reduced during the study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: All adverse events will be reported by count of events (safety and tolerability )
time frame: Up to 12 months
description: All adverse events will be reported to AstraZeneca and the IRB in accordance with the policy of National Jewish Health and the FDA. Serious adverse events, whether or not considered related to the investigational drug, will be recorded on the SAE event form will be sent to AstraZeneca within 24 hours of submission to the FDA.
measure: Change in corticosteroid dosage
time frame: Up to 12 months
description: Change in steroid dose will be assessed by comparing the corticosteroid dose to subjects at the end of the steroid stable phase and compare to steroid dose at the end of treatment period.
measure: Change in the rate of EGPA exacerbations during the study period.
time frame: Up to 12 months
description: Change in the rate of exacerbations will be assessed by comparing the rate of exacerbations during the study period with the rate during the washout and safety-monitoring period as well as with the self-reported rate of exacerbations from the year prior to the study.
arm group label: Open-Label
arm group type: Other
description: All subjects will receive the study medication- benralizumab
intervention type: Drug
intervention name: Benralizumab
description: one injection 30 mg under the subjects skin every 4 weeks for 8 weeks and then every 8 weeks for 24 weeks for a total of 5 treatments.
arm group label: Open-Label
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Michael Wechsler, MD
role: Principal Investigator
affiliation: National Jewish Health
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: National Jewish Health
investigator full name: Michael Wechsler, MD
investigator title: Prinicipal Investigator
mesh term: Systemic Vasculitis
mesh term: Benralizumab
sharing ipd: No