Effectiveness of mRNA-1273 Variant-Containing Vaccine Formulation Against Severe Outcomes in Adults Aged 50-64 Years Without Risk Factors for Severe COVID-19 (DAN-COVID)

A Phase 4 Pragmatic, Randomized Trial to Evaluate the Effectiveness of mRNA-1273 Variant-Containing Vaccine Formulation Against Severe Outcomes in Adults Aged 50-64 Years Without Risk Factors for Severe COVID-19

The purpose of this pragmatic randomized trial is to evaluate the vaccine effectiveness of the COVID-19 vaccine, mRNA-1273, in adults aged 50-64 years without known risk factors for severe COVID-19 infection. Participants will be randomized 1:1 to either COVID-19 vaccine or no COVID-19 vaccine.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19
• Intervention / Treatment: Biological: mRNA-1273 (Moderna COVID-19 vaccine)

Detailed Description

The study is a pragmatic, registry-based, open-label, individually randomized trial. The Danish nationwide administrative health registries will be used for data collection including baseline information, follow-up data, and safety monitoring. The study aims to randomize a total of 285,000 participants. Participants will be individually randomized 1:1 to receive either a COVID-19 vaccine or no COVID-19 vaccine. The study is designed to assess the vaccine effectiveness of the COVID-19 vaccine vs. no COVID-19 vaccine on the risk of medically attended COVID-19 infection.

• Study Type: Interventional
• Enrollment (Estimated): 285000
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte
  • Søborg, Denmark, 2860
    • Danske Lægers Vaccinations Service

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 50-64 years
• Informed consent form has been signed and dated

Exclusion Criteria:

• Medical conditions that increase the risk of severe COVID-19, which will be assessed through self-reporting. These medical conditions include:

  1. Asthma
  2. Cancer (excluding non-melanoma skin cancer)
  3. Cardiomyopathies
  4. Cerebrovascular disease
  5. Chronic kidney disease
  6. Chronic lung disease
  7. Cystic Fibrosis
  8. Dementia
  9. Diabetes
  10. Down syndrome
  11. Heart failure
  12. Human Immunodeficiency Virus
  13. Immunosuppressive therapy
  14. Ischemic heart disease
  15. Liver disease
  16. Neurological/neuromuscular disease
  17. Psychiatric disease (psychotic, schizophrenic, schizotypal, depressive, and bipolar (affective) disorders).
  18. Severe obesity (body mass index >35 kg/m2)
  19. Severe substance abuse
  20. Short bowel syndrome
  21. Solid organ transplant or hematological transplant
• Apart from these, there are no specific exclusion criteria for this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mRNA-1273 (Spikevax); COVID-19 vaccine single injection at day 0	Biological: mRNA-1273 (Moderna COVID-19 vaccine); For this arm, the current variant formulation of Spikevax (mRNA-1273) vaccine will be used.
No Intervention: No COVID-19 vaccine (control); Control arm, no COVID-19 vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medically attended COVID-19	Defined as a positive PCR test for SARS-CoV-2 or hospitalization for COVID-19-related respiratory tract disease	≥14 days after initially booked study visit date until 6 months after initially booked study visit date

Secondary Outcome Measures

Outcome Measure	Time Frame
COVID-19-related hospitalization	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
COVID-19-related respiratory tract disease hospitalization	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
COVID-19-related cardio-respiratory disease hospitalization	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
All-cause respiratory tract disease hospitalization	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
All-cause cardio-respiratory hospitalization	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
All-cause lower respiratory tract disease hospitalization	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
All-cause hospitalization	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
COVID-19 death	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
All-cause death	≥14 days after initially booked study visit date until 6 months after initially booked study visit date

Other Outcome Measures

Outcome Measure	Time Frame
COVID-19-related hospitalization (alternate definition)	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
Laboratory-confirmed COVID-19	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
Total length of hospital stays due to COVID-19-related respiratory tract disease	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
Composite of hospitalization for COVID-19 or pneumonia (ICD-10 codes only)	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
Hospitalization for any cardiovascular disease	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
Hospitalization due to any infectious disease	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
Hospitalization requiring mechanical ventilation	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
In-hospital mortality	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
Cardio-respiratory mortality	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
Respiratory mortality	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
Cardiovascular mortality	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
Intensive care unit admission	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
Laboratory-confirmed COVID-19 hospitalization	≥14 days after initially booked study visit date until 6 months after initially booked study visit date
Any hospital contact associated with laboratory-confirmed COVID-19	≥14 days after initially booked study visit date until 6 months after initially booked study visit date

Collaborators and Investigators

• Sponsor: Tor Biering-Sørensen
• Collaborators: ModernaTX, Inc.
• Investigators: Study Chair: Tor Biering-Sørensen, MD, MSc, MPH, PhD, Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: November 28, 2025
• First Submitted That Met QC Criteria: December 11, 2025
• First Posted (Actual): December 12, 2025

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: COVID-19; Cardiovascular; Vaccination; Registry; Respiratory; Respiratory tract disease; Pragmatic
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Respiratory Tract Diseases; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; COVID-19 Vaccines; Antigens; 2019-nCoV Vaccine mRNA-1273
• Other Study ID Numbers: DAN-COVID; 2025-523841-82-00 (Other Identifier: EU Clinical Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In this trial, baseline and endpoint data will be collected from Danish administrative health registries, which are subject to Danish legislation and can only be made available to a third party under certain conditions. Please contact the sponsor-investigator in case of any inquiries.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes