National Cohort Study of Effectiveness and Safety of SARS-CoV-2/COVID-19 Vaccines (ENFORCE)

Phase 4

Completed

• Conditions: SARS-CoV Infection
• Interventions: Biological: COMIRNATY - BioNTech Manufacturing GmbH; Biological: COVID-19 Vaccine Moderna dispersion for injection - MODERNA BIOTECH; Biological: COVID-19 Vaccine AstraZeneca suspension for injection

• Registration Number: NCT04760132
• Lead Sponsor: Jens D Lundgren, MD

Brief Summary

National cohort study of effectiveness and safety of SARS-CoV-2 vaccines (ENFORCE is an equivalence trial to evaluate the effectiveness and safety of multiple new SARS-CoV-2 vaccines approved for use in the EU, and which are being offered at participating units.

The design is an open-labelled, non-randomised, parallel group, phase IV study with historical controls.

A sub-study will be embedded within this master protocol addressing basic and translational research questions requiring additional sampling of biological material (under separate participant informed consent).

Detailed Description

First phase will enrol 10,000 persons initiating vaccination (assuming 4 vaccines). If more vaccines become available additional 2,500 persons per vaccine will be included. Subsequent phases with larger sections of the population included may be implemented.

Participants will have 6 study visits and be followed for 2 years after the first vaccination, which offers the participants an extra close follow up on vaccine effectiveness. Safety data will be collected at study visits until 3 months after the first vaccination. Research samples will be collected at each study visit during the two year follow-up

Study Timeline

• Study Start: 2021-02-08
• Study First Submitted: 2021-02-08
• Study First Submitted QC: 2021-02-17
• Study First Posted: 2021-02-18
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-10
• Last Update Posted: 2024-04-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7600

Inclusion Criteria

1. Written informed consent obtained before any trial related procedures are performed
2. Male or female eligible for SARS-CoV-2 immunization (as defined by SST in the national vaccination plan)
3. The subject must be willing and able to comply with trial protocol (re-visits and biological samples)

Exclusion Criteria

1. Male and female under the age of 18
2. Any subgroup of individuals for which the vaccines are contraindicated
3. Previous SARS-CoV-2 vaccination

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vaccine A - COMIRNATY COVID-19 vaccine	COMIRNATY - BioNTech Manufacturing GmbH	COMIRNATY (COVID-19, mRNA Vaccine) by BioNTech Manufacturing GmbH Marketing Authorisation EU/1/20/1528
Vaccine B - Moderna COVID-19 vaccine	COVID-19 Vaccine Moderna dispersion for injection - MODERNA BIOTECH	COVID-19 Vaccine Moderna dispersion for injection (COVID-19, mRNA Vaccine) by MODERNA BIOTECH SPAIN S.L. Marketing Authorisation EU/1/20/1507/001
Vaccine C - Astra-Zeneca COVID-19 vaccine	COVID-19 Vaccine AstraZeneca suspension for injection	COVID-19 Vaccine AstraZeneca suspension for injection (ChAdOx1-S \[recombinant\]) by AstraZeneca AB Marketing Authorisation EU/1/21/1529/001 and /002

Primary Outcome Measures

Name	Time	Method
Assessment of the effectiveness of citizens being vaccinated with one of the SARS-CoV-2 vaccines	The change from Base-line in MPNAT measured via profiling of antibodies against SARS-CoV-2 Spike epitopes at 24 month	Primary outcome is the minimal protective neutralising antibody titre (MPNAT); i.e. the minimum level of neutralising antibodies sufficient to protect the person from becoming infected.

Secondary Outcome Measures

Name	Time	Method
Number of breakthrough infections in the 24 months period will be used to compare the effectiveness between the vaccines	The change from first vaccination until 24 month	Number of confirmed positive SARS-CoV-2 tests reported via the national testing system.
Assessment of any Adverse Event from the vaccines will be compared between groups	From first vaccine until Day 90	Reports of participants with grade 3 and 4 Adverse Events and any Serious Adverse will be collected
Assessment of the safety of the vaccines will be compared between groups	From first vaccine until Day 90	Reports of participants with local and systemic reactions to the vaccination will be collected

Trial Locations

Locations (5)

Aarhus Universitetshospital, Skejby; 🇩🇰 Aarhus, Aarhus N, Denmark

Aalborg Universityhospital Syd; 🇩🇰 Aalborg, Denmark

Hvidovre Hospital; 🇩🇰 Hvidovre, Denmark

Odense Universityhospital; 🇩🇰 Odense, Denmark

Sjællandsuniversitetshospital; 🇩🇰 Roskilde, Denmark