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

Study Overview
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Brief Summary
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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
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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

Official Title
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National Cohort Study of Effectiveness and Safety of SARS-CoV-2/COVID-19 Vaccines

Conditions
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SARS-CoV Infection

Intervention / Treatment
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* Biological: COMIRNATY - BioNTech Manufacturing GmbH
* Biological: COVID-19 Vaccine Moderna dispersion for injection - MODERNA BIOTECH
* Biological: COVID-19 Vaccine AstraZeneca suspension for injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent obtained before any trial related procedures are performed Male or female eligible for SARS-CoV-2 immunization (as defined by SST in the national vaccination plan) The subject must be willing and able to comply with trial protocol (re-visits and biological samples) Exclusion Criteria: Male and female under the age of 18 Any subgroup of individuals for which the vaccines are contraindicated Previous SARS-CoV-2 vaccination

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The design is an open-labelled, non-randomised, parallel group, phase IV study with historical controls.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vaccine A - COMIRNATY COVID-19 vaccine<br>COMIRNATY (COVID-19, mRNA Vaccine) by BioNTech Manufacturing GmbH Marketing Authorisation EU/1/20/1528 | Biological: COMIRNATY - BioNTech Manufacturing GmbH<br>* Vaccination as part of the the Danish national government programme<br>|
| Active Comparator: Vaccine B - Moderna COVID-19 vaccine<br>COVID-19 Vaccine Moderna dispersion for injection (COVID-19, mRNA Vaccine) by MODERNA BIOTECH SPAIN S.L. Marketing Authorisation EU/1/20/1507/001 | Biological: COVID-19 Vaccine Moderna dispersion for injection - MODERNA BIOTECH<br>* Vaccination as part of the the Danish national government programme<br>|
| Active Comparator: Vaccine C - Astra-Zeneca COVID-19 vaccine<br>COVID-19 Vaccine AstraZeneca suspension for injection (ChAdOx1-S [recombinant]) by AstraZeneca AB Marketing Authorisation EU/1/21/1529/001 and /002 | Biological: COVID-19 Vaccine AstraZeneca suspension for injection<br>* Vaccination as part of the the Danish national government programme<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the effectiveness of citizens being vaccinated with one of the SARS-CoV-2 vaccines | 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. | The change from Base-line in MPNAT measured via profiling of antibodies against SARS-CoV-2 Spike epitopes at 24 month | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccination, COVID-19