EU Secondary Data Post-Authorisation Safety Study of AZD1222 (D8111R00006)

A Post-authorisation/Post-marketing Observational Study to Evaluate the Association Between Exposure to AZD1222 and Safety Concerns Using Existing Secondary Health Data Sources

A study based on electronic heath records will evaluate the incidence and relative risk of safety concerns and adverse events of special interest (AESIs) following immunisation by AZD1222 in the real-world setting.

A cohort and a self-controlled case series desings will be used.

Study Overview

• Status: Completed
• Conditions: COVID-19, Vaccine Adverse Events of Special Interest
• Intervention / Treatment: Biological: AZD1222

Detailed Description

This retrospective study based on electronic heath records will evaluate the incidence and relative risk of safety concerns and adverse events of special interest (AESIs) following immunisation by AZD1222 in the real-world setting. The primary study objectives are to (1) describe baseline characteristics of all individuals in the matched population over the study period; (2) describe, among subjects who receive a first dose of AZD1222, the timing and type of second dose of any COVID-19 vaccine over the study period; (3) describe the incidence of prespecified AESIs in subjects who have received at least one dose of AZD1222 in the matched population and unvaccinated subjects; and (4) estimate any increased risk of prespecified AESIs following vaccination with AZD1222 using study retrospective cohort and self-controlled risk interval designs. Secondary objectives are identical to the primary, although focused on specific populations considered to have missing information, specifically (a) women who are pregnant or breastfeeding, (b) immunocompromised patients, (b) frail patients with certain comorbidities, (c) patients with autoimmune or inflammatory disorders, and (d) patients who, at cohort entry, had recently received a number of selected vaccines to prevent diseases other than COVID-19. A cohort and a self-controlled case series designs will be used.

Exploratory objectives: 1) To describe the IRs of prespecified AESIs in subjects who received an mRNA vaccine against COVID-19 (either Comirnaty or Spikevax) (active comparators) and in subjects from the pre-pandemic period (2017-2018) (historical comparators) in the matched population; 2) To estimate the relative and absolute risk of prespecified AESIs in subjects who received at least 1 dose of AZD1222 in the matched population compared with historical comparators in the matched population; and 3) To estimate the relative and absolute risk of prespecified AESIs in subjects who received 2 doses of AZD1222 in the matched population compared with subjects who received 2 doses of active comparator (Comirnaty or Spikevax as per homologous vaccination regimen) in the matched population*

*Feasibility of the active comparator analysis will be assessed prior to conducting the analysis to ensure comparability between groups.

• Study Type: Observational
• Enrollment (Actual): 5321930

Contacts and Locations

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

Study Locations

• Netherlands
  • Utrecht, Netherlands, 3528 AE
    • Research Site
• Spain
  • Barcelona, Spain, 8007
    • Research Site
  • Valencia, Spain, 46020
    • Research Site
• United Kingdom
  • Southampton, United Kingdom, SO31 1AA
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will include subjects who are exposed to the AZD1222 vaccine and 3 comparator groups: concurrent subjects who have not received any SARS-CoV-2 vaccine, historical controls, and active comparators*

*Feasibility of the active comparator analysis will be assessed prior to conducting the analysis to ensure comparability between groups

Description

Inclusion criteria for AZD1222, unvaccinated, and active comparators*:

• Have at least 12 months of data available before the index date
• Have no record of vaccination with any other COVID-19 vaccine on or before the index date

Inclusion criteria for historical comparators:

- Have at least 12 months of data available before the index date

Exclusion criteria:

For each AESI, subjects (in any matched cohort) who had a specific AESI during the look-back period before the index date will be excluded from the cohort for the analysis of that specific AESI, but not from the cohorts for analysis of other AESIs.

- If a subject had a specific AESI between the index date and the start of the risk window or had any censoring criteria within this time period, the subject will be excluded from the analysis of that specific AESI.

*Feasibility of the active comparator analysis will be assessed prior to conducting the analysis to ensure comparability between groups

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
AZD1222; at least one dose of AZD1222	Biological: AZD1222; Covid-19 AstraZeneca Vaccine
comparator 1; concurrent unvaccinated
comparator 2; historical controls
comparator 3; active comparators* *Feasibility of the active comparator analysis will be assessed prior to conducting the analysis to ensure comparability between groups

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events of special interest	several AESIs	up to 365 days

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: RTI Health Solutions
• Investigators: Principal Investigator: Cristina Rebordosa, MD, PhD, RTI

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2022
• Primary Completion (Actual): January 24, 2024
• Study Completion (Actual): January 24, 2024

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: November 9, 2021
• First Posted (Actual): November 19, 2021

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: AZD1222; ChAdOx1nCoV-19; Vaccine Adverse Events of Special Interest
• Other Study ID Numbers: D8111R00006

Plan for Individual participant data (IPD)

Study Data/Documents

1. URL
   Information identifier: EUPAS Register
   Information comments: EUPAS Register

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No