A Non-interventional Multi-country Cohort Study to Assess the Safety of EVUSHELD™ During Pregnancy (O-STEREO)

A Non-interventional Multi-country Cohort Study to Assess the Safety of EVUSHELD™ (Tixagevimab/Cilgavimab) During Pregnancy

Multi-country, non-interventional cohort study.The objective of the study is to characterise the risk of pregnancy and offspring (neonatal and infant) outcomes in pregnancies with and without exposure to EVUSHELD (used as a treatment or prophylaxis) among women of child-bearing indicated for such treatment in the real-world setting, using secondary data from US, France and Canada.

Study Overview

• Status: Withdrawn
• Conditions: Pregnancy; Pregnant Women; Pregnancy Outcome

Detailed Description

This is a multi-country, non-interventional cohort study in pregnancies exposed to EVUSHELD and pregnancies unexposed to EVUSHELD among women eligible for EVUSHELD. The study will be conducted within secondary data sources (administrative claims, electronic medical records (EMR) and/or registry data). For each country, the overall study period will span 12 months prior to the country-specific EVUSHELD availability until the end of the data cut or 31 March 2027, whichever is earlier.

The study will include pregnancies in individuals eligible for EVUSHELD therapy in each country in the selected datasets, including pregnant individuals aged 18 to 49 years with a high-risk condition documented in the 12 months prior to the start of the pregnancy, defined as the first day of the last menstrual period (LMP).

• Study Type: Observational

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study will include pregnancies in individuals eligible for EVUSHELD administration in each country, including pregnant females aged 18-49 years with a high-risk condition. Exposed and unexposed pregnancies will be identified from this population for outcome-specific analyses.

EVUSHELD indication varies from one country to another and may evolve over the course of the study. In order to have a homogeneous study population and maximise its size, all countryspecific EVUSHELD eligibility criteria at the time of protocol development were considered to define the study population.

Description

Inclusion Criteria:

• Female sex at LMP
• Age 18-49 years at LMP
• Continuous coverage/clinical activity (dependent on data source type) within the confounder ascertainment period
• LMP date falls within the LMP eligibility period
• Occurrence of at least one of the following high-risk conditions during the confounder ascertainment period

• Immunocompromised conditions:

  • Cancer (active solid cancer, blood cancer, or receipt of chemotherapy, immunotherapy, or radiotherapy)
  • Solid organ transplant
  • HIV/AIDS
  • Prolonged systemic corticosteroid use (15-20 mg of prednisone equivalents for greater than 2 weeks)
  • Receipt of T or B cell depleting therapy, anti-Tumour Necrosis Factor (anti- TNF), or other immunosuppressive agents
  • Receipt of stem cell transplant
  • Receipt of gene cell therapy of the CAR-T cell type
  • Congenital immunodeficiency, primary immune deficiencies (treatment with subcutaneous or intravenous immunoglobulins - and/or immunodeficiency diagnosis codes), severe or combined immunodeficiency (including transplanted
  • Severe combined immunodeficiency [SCID] where immunoglobulin replacement is required)
  • Other autoimmune conditions and immune-mediated inflammatory disorders (such as systemic lupus erythematosus, Crohn's disease, ulcerative colitis).

• Conditions that increase risk of COVID-19 disease progression

  • Severe risk of COVID-19 disease progression: sickle cell disease, chronic lung disease (ie, chronic bronchitis, Chronic obstructive pulmonary disease [COPD], cystic fibrosis, emphysema with dyspnoea on exertion), chronic kidney disease, cardiovascular diseases (ie, heart failure, coronary artery disease, cardiomyopathies), moderate to severe asthma, Down syndrome, rare neurological conditions (ie, multiple sclerosis, motor neurone disease, myasthenia gravis, Huntington's disease), gestational diabetes requiring medication
  • Moderate risk of COVID-19 disease progression: type I or II diabetes, obesity, chronic liver disease, congenital heart disease

Exclusion Criteria:

• Multifoetal pregnancies are defined by the presence of any International Classification of Diseases (ICD-10) diagnosis code, any position indicating presence of more than one foetus (see code list) on the hospital record throughout the pregnancy episode
• Use of in vitro fertilisation or other assisted reproductive technology in the 36 weeks prior LMP as identified by ICD-10 diagnosis code "pregnancy resulting from assisted reproductive technology" or related procedure codes indicating in vitro fertilisation (IVF) or assisted reproductive technology (ART) (see code list) on the electronic health records (EHR) or hospital claims records 36 weeks prior to LMP

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Evusheld exposed pregnancies; A pregnancy is considered exposed to EVUSHELD if 1 of 2 conditions are met: (1) EVUSHELD was received during the 36-week period [reflective of roughly 3 half-lives of EVUSHELD] prior to LMP, or (2) EVUSHELD was received on/after LMP during the exposure ascertainment period, which will vary based on the outcome of interest.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk of pregnancy outcomes potentially associated with exposure in early pregnancy and measured prior to 20 weeks gestation	Spontaneous abortion, Ectopic pregnancy	Index date to < 20 weeks of gestation
Risk of pregnancy outcomes potentially associated with exposure anytime during pregnancy and measured anytime during pregnancy	Maternal Death	Index date to end of pregnancy (Note: Maternal death outcome ascertainment period is up to 42 days after the end of pregnancy episode (EPE).)
Risk of pregnancy outcomes potentially associated with exposure anytime during pregnancy and measured after 20 weeks gestation	Preterm live birth, Stillbirth, Gestational hypertension, Pre-eclampsia, Gestational diabetes	Index date to end of pregnancy Note: For preterm birth, the outcome ascertainment period is 20 to 37 weeks of gestation
Risk of outcomes in neonates potentially associated with exposure anytime during pregnancy and measured 28 days after birth	Low birth weight, Small for gestational age, Respiratory distress syndrome in the newborn, Neonatal death	Diagnosed within 28 days of birth
Risk of outcomes in infants potentially associated with exposure anytime during pregnancy and measured within 12 months after birth	Major congenital malformations, Infant death, Failure to thrive	From birth to time of death or 12 months of age

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Aetion, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 27, 2022
• Primary Completion (Estimated): January 31, 2024
• Study Completion (Estimated): January 31, 2024

Study Registration Dates

• First Submitted: February 21, 2023
• First Submitted That Met QC Criteria: May 4, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Pregnancy outcome; evusheld; pregnancy exposure; immunocompromised condition
• Other Study ID Numbers: D8850R00006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.