<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/NCT03794999</url>
  </required_header>
  <id_info>
    <org_study_id>D3250R00026</org_study_id>
    <secondary_id>EUPAS26461</secondary_id>
    <nct_id>NCT03794999</nct_id>
  </id_info>
  <brief_title>Benralizumab Pregnancy Exposure Study</brief_title>
  <official_title>The Benralizumab Pregnancy Exposure Study: A VAMPSS Post Marketing Surveillance Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective, observational, exposure cohort study of pregnancy and infant outcomes&#xD;
      in women with asthma exposed to benralizumab anytime during pregnancy, or within 8 weeks&#xD;
      prior to the first day of the last menstrual period (LMP)&#xD;
&#xD;
      The objective of the study is to monitor planned or unplanned pregnancies to evaluate&#xD;
      potential teratogenic effect (birth defect) when exposed to benralizumab compared to two&#xD;
      unexposed comparator groups.&#xD;
&#xD;
      The primary outcome is major structural birth defects (abnormalities in development of&#xD;
      structures of the body) and the secondary outcomes are preterm delivery (premature baby),&#xD;
      small for gestational age infants (small for weight, length, and/or head circumference),&#xD;
      spontaneous abortion (miscarriage), stillbirth (baby born without signs of life), elective&#xD;
      termination (voluntary abortion) and small for age postnatal growth to one year of age (small&#xD;
      for weight, length and/or head circumference). The birth prevalence or incidence of outcomes&#xD;
      in women exposed to benralizumab, and their infants, will be compared to those observed in&#xD;
      two unexposed comparator groups: a disease-matched comparison group of women who have not&#xD;
      used benralizumab during pregnancy or within 8 weeks of their last menstrual period (LMP),&#xD;
      but who have used other anti-asthmatic medications (treated disease comparison group), and a&#xD;
      comparison group of healthy women who do not have a diagnosis of asthma, have not had&#xD;
      exposure to a known human teratogen (substance that causes birth defect), and have not taken&#xD;
      benralizumab in pregnancy (healthy comparison group).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 20, 2019</start_date>
  <completion_date type="Anticipated">February 27, 2026</completion_date>
  <primary_completion_date type="Anticipated">February 27, 2026</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>20 Months</target_duration>
  <primary_outcome>
    <measure>Major structural birth defects</measure>
    <time_frame>Up to 1 year of age</time_frame>
    <description>Pregnancies ending in live birth with exposure in the first trimester for benralizumab cohort, and other comparison groups at least one malformed infant in an individual pregnancy is considered one malformed outcome</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Spontaneous abortion/miscarriage</measure>
    <time_frame>Prior to 20.0 weeks gestation</time_frame>
    <description>Spontaneous pregnancy loss prior to 20.0 weeks gestation, since women only enrol after recognition of pregnancy, spontaneous abortions are only identified after enrolment in clinically recognised pregnancies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Preterm delivery</measure>
    <time_frame>Prior to 37 weeks of gestation</time_frame>
    <description>Pregnancies enrolled prior to 37.0 weeks' gestation and ending in at least one live born infant. Excludes twins or higher order multiples due to inherent higher risk of preterm birth in multiples. Exposure can occur any time in pregnancy prior to the event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Small for gestational age infants</measure>
    <time_frame>At birth</time_frame>
    <description>Pregnancies ending in at least one live born infant who are &lt;10th centile on birth weight, length and/or head circumference for infant sex and gestational age; excluding twins or higher order multiples due to the inherent higher risk of reduced birth size in multiples. Exposure can occur any time in pregnancy prior to the event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stillbirth</measure>
    <time_frame>At delivery</time_frame>
    <description>Stillbirth is defined as a fetal death that occurs &gt;20 weeks' gestation. All pregnancies, excluding lost-to-follow-up. Exposure can occur any time in pregnancy prior to the event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elective termination/abortion</measure>
    <time_frame>At the end of pregnancy, or through 9 month pregnancy period</time_frame>
    <description>Elective termination is defined as deliberate interruption of pregnancy by surgical or medical means. All pregnancies, excluding lost-to-follow-up. Exposure can occur anytime in pregnancy prior to the event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Small for age postnatal growth of live born children to 1 year of age</measure>
    <time_frame>Up to one year of age</time_frame>
    <description>Postnatal growth is measured at approximately 1 year of age among live born infants and age and sex specific percentiles assigned using standard U.S. growth curves. Weight, length and/or head circumference &lt;10th centile will be considered small for age. Multiples are excluded. Exposure can occur anytime in pregnancy.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">800</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Benralizumab-exposed group</arm_group_label>
    <description>Pregnant women with asthma exposed to benralizumab anytime during pregnancy or within 8 weeks prior to last menstrual period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Asthmatic comparison group</arm_group_label>
    <description>Pregnant women currently treated for asthma not exposed to benralizumab during pregnancy or within 8 weeks prior to last menstrual period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-asthmatic comparison group</arm_group_label>
    <description>Pregnant women who are not diagnosed with asthma, have not had exposure to a known human teratogen, and have not taken benralizumab during pregnancy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Benralizumab-exposure</intervention_name>
    <description>Exposure is defined as any dose of benralizumab for any length of time from 8 weeks prior to Last Mentrual Period (LMP) through the end of pregnancy, as reported by the mother and validated through medical record review. The 8-week cut-off prior to LMP is based upon the terminal half-life of benralizumab of approximately 15 days (clearance of benralizumab is based on five half-lives).</description>
    <arm_group_label>Benralizumab-exposed group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exposure to other asthma medications</intervention_name>
    <description>Exposure to asthma medications for any number of days, at any dose, and at any time from LMP up to the date of enrollment, but no exposure to benralizumab during pregnancy or within 8 weeks prior to LMP.</description>
    <arm_group_label>Asthmatic comparison group</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study population includes pregnant women who reside in the US or Canada who have or&#xD;
        have not used benralizumab anytime in pregnancy for asthma.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Participants will be recruited into the three cohorts concurrently, on the basis of the&#xD;
        following inclusion/exclusion criteria:&#xD;
&#xD;
        Cohort 1: Benralizumab-Exposed&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Currently pregnant women diagnosed with asthma who contact the OTIS Research Center&#xD;
             and who have been exposed to benralizumab for any number of days, at any dose, and at&#xD;
             any time from 8 weeks before the first day of LMP up to and including the end of&#xD;
             pregnancy.&#xD;
&#xD;
          -  Eligible participants will be currently pregnant women who agree to the conditions and&#xD;
             requirements of the study including the interview schedule and release of medical&#xD;
             records.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who have had exposure to another biologic, used for any indication, anytime&#xD;
             during pregnancy or within 8 weeks of LMP.&#xD;
&#xD;
          -  Women will not be eligible for Cohort 1 if they first contact the OTIS Research Center&#xD;
             after prenatal diagnosis of a major structural birth defect.&#xD;
&#xD;
          -  Restrospective cases (outcome of pregnancy known prior to enrollment).&#xD;
&#xD;
          -  Women who have enrolled in the current study with a previous pregnancy.&#xD;
&#xD;
        Cohort 2: Treated Diseased Comparison&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Currently pregnant women diagnosed with asthma and exposed to asthma medications for&#xD;
             any number of days, at any dose, and at any time from LMP up to the date of&#xD;
             enrollment, who contact the OTIS Research Center but who were not exposed to&#xD;
             benralizumab during pregnancy or within 8 weeks prior to LMP.&#xD;
&#xD;
          -  Eligible participants will be currently pregnant women who agree to the conditions and&#xD;
             requirements of the study including the interview schedule and release of medical&#xD;
             records.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women with exposure to benralizumab any time during pregnancy or within 8 weeks prior&#xD;
             to LMP.&#xD;
&#xD;
          -  Women will not be eligible for Cohort 2 if they first come in contact with the OTIS&#xD;
             Research Center after prenatal diagnosis of a major structural birth defect.&#xD;
&#xD;
          -  Retrospective cases (outcome of pregnancy known prior to enrollment).&#xD;
&#xD;
          -  Women who have enrolled in the current study with a previous pregnancy.&#xD;
&#xD;
        Cohort 3: Non-Asthmatic Comparison&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Currently pregnant women who contact the OTIS Research Center.&#xD;
&#xD;
          -  Eligible women may potentially have been exposed to non-teratogenic agents during this&#xD;
             pregnancy.&#xD;
&#xD;
          -  Women who agree to the conditions and requirements of the study including the&#xD;
             interview schedule and release of medical records.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who have been exposed to any known teratogenic agents as determined by the OTIS&#xD;
             Research Center (list in Annex 1) for any number of days, at any dose, from the first&#xD;
             day of the last menstrual period up to and including the end of pregnancy.&#xD;
&#xD;
          -  Women with a self-reported diagnosis of asthma, current or previous.&#xD;
&#xD;
          -  Women will not be eligible for Cohort 3 if they come in contact with the OTIS Research&#xD;
             Center after prenatal diagnosis of a major structural birth defect.&#xD;
&#xD;
          -  Retrospective cases (outcome of pregnancy known prior to enrollment).&#xD;
&#xD;
          -  Women who have enrolled in the current study with a previous pregnancy.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>Pregnant women who have or have not used benralizumab anytime in pregnancy for asthma.</gender_description>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christina Chambers, PhD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Diego</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>AstraZeneca Clinical Study Information Center</last_name>
    <phone>1-877-240-9479</phone>
    <email>information.center@astrazeneca.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 4, 2018</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>August 22, 2023</last_update_submitted>
  <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>asthma</keyword>
  <keyword>pregnancy</keyword>
  <keyword>benralizumab</keyword>
  <keyword>infant</keyword>
  <keyword>teratogenic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</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/NCT03794999
org study id: D3250R00026
secondary id: EUPAS26461
nct id: NCT03794999
lead sponsor: 
collaborator: 
has dmc: Yes
This is a prospective, observational, exposure cohort study of pregnancy and infant outcomes
      in women with asthma exposed to benralizumab anytime during pregnancy, or within 8 weeks
      prior to the first day of the last menstrual period (LMP)

      The objective of the study is to monitor planned or unplanned pregnancies to evaluate
      potential teratogenic effect (birth defect) when exposed to benralizumab compared to two
      unexposed comparator groups.

      The primary outcome is major structural birth defects (abnormalities in development of
      structures of the body) and the secondary outcomes are preterm delivery (premature baby),
      small for gestational age infants (small for weight, length, and/or head circumference),
      spontaneous abortion (miscarriage), stillbirth (baby born without signs of life), elective
      termination (voluntary abortion) and small for age postnatal growth to one year of age (small
      for weight, length and/or head circumference). The birth prevalence or incidence of outcomes
      in women exposed to benralizumab, and their infants, will be compared to those observed in
      two unexposed comparator groups: a disease-matched comparison group of women who have not
      used benralizumab during pregnancy or within 8 weeks of their last menstrual period (LMP),
      but who have used other anti-asthmatic medications (treated disease comparison group), and a
      comparison group of healthy women who do not have a diagnosis of asthma, have not had
      exposure to a known human teratogen (substance that causes birth defect), and have not taken
      benralizumab in pregnancy (healthy comparison group).
observational model: Cohort
time perspective: Prospective
measure: Major structural birth defects
time frame: Up to 1 year of age
description: Pregnancies ending in live birth with exposure in the first trimester for benralizumab cohort, and other comparison groups at least one malformed infant in an individual pregnancy is considered one malformed outcome
measure: Spontaneous abortion/miscarriage
time frame: Prior to 20.0 weeks gestation
description: Spontaneous pregnancy loss prior to 20.0 weeks gestation, since women only enrol after recognition of pregnancy, spontaneous abortions are only identified after enrolment in clinically recognised pregnancies.
measure: Preterm delivery
time frame: Prior to 37 weeks of gestation
description: Pregnancies enrolled prior to 37.0 weeks' gestation and ending in at least one live born infant. Excludes twins or higher order multiples due to inherent higher risk of preterm birth in multiples. Exposure can occur any time in pregnancy prior to the event.
measure: Small for gestational age infants
time frame: At birth
description: Pregnancies ending in at least one live born infant who are <10th centile on birth weight, length and/or head circumference for infant sex and gestational age; excluding twins or higher order multiples due to the inherent higher risk of reduced birth size in multiples. Exposure can occur any time in pregnancy prior to the event.
measure: Stillbirth
time frame: At delivery
description: Stillbirth is defined as a fetal death that occurs >20 weeks' gestation. All pregnancies, excluding lost-to-follow-up. Exposure can occur any time in pregnancy prior to the event.
measure: Elective termination/abortion
time frame: At the end of pregnancy, or through 9 month pregnancy period
description: Elective termination is defined as deliberate interruption of pregnancy by surgical or medical means. All pregnancies, excluding lost-to-follow-up. Exposure can occur anytime in pregnancy prior to the event.
measure: Small for age postnatal growth of live born children to 1 year of age
time frame: Up to one year of age
description: Postnatal growth is measured at approximately 1 year of age among live born infants and age and sex specific percentiles assigned using standard U.S. growth curves. Weight, length and/or head circumference <10th centile will be considered small for age. Multiples are excluded. Exposure can occur anytime in pregnancy.
arm group label: Benralizumab-exposed group
description: Pregnant women with asthma exposed to benralizumab anytime during pregnancy or within 8 weeks prior to last menstrual period
arm group label: Asthmatic comparison group
description: Pregnant women currently treated for asthma not exposed to benralizumab during pregnancy or within 8 weeks prior to last menstrual period
arm group label: Non-asthmatic comparison group
description: Pregnant women who are not diagnosed with asthma, have not had exposure to a known human teratogen, and have not taken benralizumab during pregnancy.
intervention type: Drug
intervention name: Benralizumab-exposure
description: Exposure is defined as any dose of benralizumab for any length of time from 8 weeks prior to Last Mentrual Period (LMP) through the end of pregnancy, as reported by the mother and validated through medical record review. The 8-week cut-off prior to LMP is based upon the terminal half-life of benralizumab of approximately 15 days (clearance of benralizumab is based on five half-lives).
arm group label: Benralizumab-exposed group
intervention type: Drug
intervention name: Exposure to other asthma medications
description: Exposure to asthma medications for any number of days, at any dose, and at any time from LMP up to the date of enrollment, but no exposure to benralizumab during pregnancy or within 8 weeks prior to LMP.
arm group label: Asthmatic comparison group
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
gender description: Pregnant women who have or have not used benralizumab anytime in pregnancy for asthma.
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Christina Chambers, PhD, MPH
role: Principal Investigator
affiliation: University of California, San Diego
last name: AstraZeneca Clinical Study Information Center
phone: 1-877-240-9479
email: information.center@astrazeneca.com
facility: 
status: Recruiting
country: United States
responsible party type: Sponsor
mesh term: Asthma
mesh term: Benralizumab
sharing ipd: No