Benralizumab Pregnancy Exposure Study

Asthma Clinical Trial

Official title:

The Benralizumab Pregnancy Exposure Study: A VAMPSS Post Marketing Surveillance Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03794999
• Other study ID #: D3250R00026
• Secondary ID: EUPAS26461
• Status: Terminated
• Start date: March 20, 2019
• Est. completion date: December 29, 2023

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 299
• Est. completion date: December 29, 2023
• Est. primary completion date: December 29, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 130 Years

Eligibility

Participants will be recruited into the three cohorts concurrently, on the basis of the following inclusion/exclusion criteria: Cohort 1: Benralizumab-Exposed

Inclusion Criteria:

• Currently pregnant women diagnosed with asthma who contact the OTIS Research Center and who have been exposed to benralizumab for any number of days, at any dose, and at any time from 8 weeks before the first day of LMP up to and including the end of pregnancy.
• Eligible participants will be currently pregnant women who agree to the conditions and requirements of the study including the interview schedule and release of medical records.

Exclusion Criteria:

• Women who have had exposure to another biologic, used for any indication, anytime during pregnancy or within 8 weeks of LMP.
• Women will not be eligible for Cohort 1 if they first contact the OTIS Research Center after prenatal diagnosis of a major structural birth defect.
• Restrospective cases (outcome of pregnancy known prior to enrollment).
• Women who have enrolled in the current study with a previous pregnancy. Cohort 2: Treated Diseased Comparison

Inclusion Criteria:

• Currently pregnant women diagnosed with asthma and exposed to asthma medications for any number of days, at any dose, and at any time from LMP up to the date of enrollment, who contact the OTIS Research Center but who were not exposed to benralizumab during pregnancy or within 8 weeks prior to LMP.
• Eligible participants will be currently pregnant women who agree to the conditions and requirements of the study including the interview schedule and release of medical records.

Exclusion Criteria:

• Women with exposure to benralizumab any time during pregnancy or within 8 weeks prior to LMP.
• Women will not be eligible for Cohort 2 if they first come in contact with the OTIS Research Center after prenatal diagnosis of a major structural birth defect.
• Retrospective cases (outcome of pregnancy known prior to enrollment).
• Women who have enrolled in the current study with a previous pregnancy. Cohort 3: Non-Asthmatic Comparison

Inclusion Criteria:

• Currently pregnant women who contact the OTIS Research Center.
• Eligible women may potentially have been exposed to non-teratogenic agents during this pregnancy.
• Women who agree to the conditions and requirements of the study including the interview schedule and release of medical records.

Exclusion Criteria:

• Women who have been exposed to any known teratogenic agents as determined by the OTIS Research Center (list in Annex 1) for any number of days, at any dose, from the first day of the last menstrual period up to and including the end of pregnancy.
• Women with a self-reported diagnosis of asthma, current or previous.
• Women will not be eligible for Cohort 3 if they come in contact with the OTIS Research Center after prenatal diagnosis of a major structural birth defect.
• Retrospective cases (outcome of pregnancy known prior to enrollment).
• Women who have enrolled in the current study with a previous pregnancy.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Benralizumab-exposure
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).
• Exposure to other asthma medications
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.

Locations

Country	Name	City	State
United States	Research Site	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	University of California, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major structural birth defects	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	Up to 1 year of age
Secondary	Spontaneous abortion/miscarriage	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.	Prior to 20.0 weeks gestation
Secondary	Preterm delivery	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.	Prior to 37 weeks of gestation
Secondary	Small for gestational age infants	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.	At birth
Secondary	Stillbirth	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.	At delivery
Secondary	Elective termination/abortion	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.	At the end of pregnancy, or through 9 month pregnancy period
Secondary	Small for age postnatal growth of live born children to 1 year of age	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.	Up to one year of age