A Study to Evaluate the Immunogenicity and Safety of Omicron Variant Vaccines in Comparison With mRNA-1273 Booster Vaccine for COVID-19

A Phase 2/3, Randomized, Observer-blind, Active-controlled, Multicenter Study to Evaluate the Immunogenicity and Safety of Omicron Variant Vaccines in Comparison With mRNA-1273 (Prototype) Booster Vaccine

This is a 2-part study to evaluate the immunogenicity, safety, and reactogenicity of mRNA-1273.529 and mRNA-1273.214 administered as a booster dose.

Study Overview

• Status: Completed
• Conditions: SARS-CoV-2
• Intervention / Treatment: Biological: mRNA-1273.214; Biological: mRNA-1273; Biological: mRNA-1273.529

Detailed Description

In Part 1, participants will be randomized in a 1:1 ratio to receive a single dose of either mRNA-1273.529 or mRNA-1273.

In Part 2, participants will be randomized in a 1:1 ratio to receive a single dose of either mRNA-1273.214 or mRNA-1273.

All participants will have previously received 2 or 3 doses of an authorized/approved COVID-19 vaccine. Participants who previously received 2 doses of a COVID-19 vaccine as a primary series will receive mRNA-1273.529, mRNA-1273.214, or mRNA-1273 as the 3rd dose, and participants who have previously received a primary series and 1 booster dose will receive mRNA-1273.529, mRNA-1273.214, or mRNA-1273 as the 4th dose (a mixed approach is acceptable). Each part will include Phase A (randomized, blinded) and Phase B (open-label, observational).

• Study Type: Interventional
• Enrollment (Actual): 3557
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital
  • London, United Kingdom, SW10 9NH
    • Chelsea And Westminster Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • London, United Kingdom, SW17 0RE
    • St. George's Hospital
  • London, United Kingdom, EC1A 7BE
    • Barts Hospital
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital
  • Aberdeenshire
    • Aberdeen, Aberdeenshire, United Kingdom, AB25 2ZD
      • Aberdeen Royal Infirmary - PPDS
  • Avon
    • Bristol, Avon, United Kingdom, BS10 5NB
      • Southmead Hospital
  • Cambridgeshire
    • Wansford, Cambridgeshire, United Kingdom, PE8 6PL
      • Wansford and Kingscliffe Practice
  • Cheshire
    • Runcorn, Cheshire, United Kingdom, WA7 2DA
      • Halton General Hospital
  • Cleveland
    • Middlesbrough, Cleveland, United Kingdom, TS4 3BW
      • The James Cook University Hospital
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Royal Cornwall Hospital
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Royal Devon and Exeter Hospital NHS Trust
  • Dorset
    • Bournemouth, Dorset, United Kingdom, BH7 7DW
      • Royal Bournemouth Hospital
  • Gloucestershire
    • Gloucester, Gloucestershire, United Kingdom, GL1 3NN
      • Gloucester Royal Hospital
  • Hampshire
    • Portsmouth, Hampshire, United Kingdom, PO1 3HN
      • Portsmouth Research Hub
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY3 7EN
      • Fylde Coast Clinical Research
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE5 4PW
      • Leicester General Hospital
  • Manchester
    • Salford, Manchester, United Kingdom
      • Salford Royal Hospital - PPDS
  • Middlesex
    • London, Middlesex, United Kingdom, WC1E 6EB
      • University College London Hospitals Covid-19 Vaccine Centre
  • North Humberside
    • Hull, North Humberside, United Kingdom, HU16 5JQ
      • Castle Hill Hospital
  • Shropshire
    • Telford, Shropshire, United Kingdom, TF1 6TF
      • The Princess Royal Hospital
  • Somerset
    • Bath, Somerset, United Kingdom, BA1 3NG
      • Royal United Hospital
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S5 7AU
      • Sheffield/Northern General Hospital
  • Wales
    • Pontyclun, Wales, United Kingdom, CF72 8XR
      • Royal Glamorgan Hospital - PPDS
  • West Yorkshire
    • Bradford, West Yorkshire, United Kingdom, BD9 6RJ
      • Bradford Institute for Health Research
  • Wiltshire
    • Swindon, Wiltshire, United Kingdom, SN3 6BB
      • Great Western Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Female participants of childbearing potential may be enrolled in the study if the participant has a negative pregnancy test at the Screening Visit and on the day of vaccination prior to vaccine dose being administered on Day 1; has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose (Day 1); and has agreed to continue adequate contraception through 90 days following vaccine administration.
• Participant has received 2 prior doses of one of the following approved/authorized COVID-19 vaccines: Moderna, Pfizer/BioNTech, Oxford/AstraZeneca, Janssen. A heterologous vaccine regimen is acceptable.
• Participants who will receive the 4th dose as part of the study must have previously received a mRNA vaccine (Moderna or Pfizer/BioNTech) as the 3rd dose of a COVID-19 vaccine. Participants who will receive the 3rd dose as part of the study may have previously received 2 doses of an approved/authorized mRNA or a non-mRNA COVID-19 vaccine (a heterologous vaccine regimen is acceptable).

Exclusion Criteria:

• Participant had close contact (without personal protective equipment [PPE]) as defined by the Centers for Disease Control and Prevention (CDC) in the past 14 days to someone diagnosed with SARS-CoV-2 infection or COVID-19 within 10 days of the close contact. Participants may be rescreened after 14 days provided that they remain asymptomatic.
• Participant is acutely ill or febrile (temperature ≥ 38.0°C/100.4°F) 72 hours prior to or at the Screening Visit or Day 1.
• Participant has tested positive for SARS-CoV-2 by an authorized/approved lateral flow/rapid antigen or polymerase chain reaction (PCR) test within 90 days of Screening.
• Participant has received a COVID-19 vaccine within 90 days of the Screening Visit.
• Participant has received a total of 4 doses or more of COVID-19 vaccine.
• Participant has received a COVID-19 vaccine at a dose different from the authorized/approved dose.
• Any medical, psychiatric, or occupational condition, including reported history of substance abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results.
• Participant has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 181 days prior to screening (for corticosteroids ≥10 milligrams [mg]/day of prednisone or equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study.
• Participant has received or plans to receive any licensed vaccine ≤28 days prior to the study injection (Day 1) or plans to receive a licensed vaccine within 28 days after the study injection (with the exception that approved seasonal influenza vaccine may be received by at least 7 days and preferably 14 days apart from the study injection).
• Participant has received systemic immunoglobulins or blood products within 90 days prior to the Screening Visit or plans to receive during the study.
• Participant has donated ≥450 milliliters (mL) of blood products within 28 days prior to the Screening Visit or plans to donate blood products during the study.
• Participant has participated in an interventional clinical study within 28 days prior to the Screening Visit based on the medical history interview or plans to do so while participating in this study.

Note: Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: mRNA-1273.529; Phase A: Participants will receive 1 intramuscular (IM) dose of mRNA-1273.529 on Day 1. Phase B: After Day 179, eligible participants may choose to be unblinded and to receive an additional booster outside of the study.	Biological: mRNA-1273.529; Sterile liquid for injection
Active Comparator: Part 1: mRNA-1273; Phase A: Participants will receive 1 IM dose of mRNA-1273 on Day 1. Phase B: After Day 179, eligible participants may choose to be unblinded and to receive an additional booster outside of the study.	Biological: mRNA-1273; Sterile liquid for injection
Experimental: Part 2: mRNA-1273.214; Phase A: Participants will receive 1 IM dose of mRNA-1273.214 on Day 1. Phase B: After Day 85, eligible participants may choose to be unblinded and to receive an additional booster outside of the study.	Biological: mRNA-1273.214; Sterile liquid for injection
Active Comparator: Part 2: mRNA-1273; Phase A: Participants will receive 1 IM dose of mRNA-1273 on Day 1. Phase B: After Day 85, eligible participants may choose to be unblinded and to receive an additional booster outside of the study.	Biological: mRNA-1273; Sterile liquid for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Geometric Mean Titer (GMT) of mRNA-1273.529 and mRNA-1273 Against the B.1.1.529 Strain	Up to Day 85 post-vaccination
Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs)	Up to Day 8 (7 days post-vaccination)
Number of Participants with Unsolicited Adverse Events (AEs)	Up to Day 29 (28 days post-vaccination)
Number of Participants with Serious AEs (SAEs)	Day 1 to end of study (Day 359)
Number of Participants with Medically Attended AEs (MAAEs)	Day 1 to end of study (Day 359)
Number of Participants with AEs Leading to Withdrawal	Day 1 to end of study (Day 359)
Number of Participants with AEs of Special Interest (AESIs)	Day 1 to end of study (Day 359)
GMT of mRNA-1273.214 and mRNA-1273 Against the B1.1.529 Strain	Up to Day 85 post-vaccination
GMT of mRNA-1273.214 and mRNA-1273 Against the Prototype Strain	Up to Day 85 post-vaccination

Secondary Outcome Measures

Outcome Measure	Time Frame
GMT of mRNA-1273.529 and mRNA-1273 Against the B.1.1.529 Strain	Days 1, 29, 85, 179, and 359
GMT of mRNA-1273.529 and mRNA-1273 Against the Prototype Strain	Days 1, 29, 85, 179, and 359
Seroresponse Rate of Vaccine Recipients	Days 1, 29, 85, 179, and 359
GMT of mRNA-1273.214 and mRNA-1273 Against Other Variant Strains	Days 29 and 85
Number of Participants with Asymptomatic SARS-CoV-2 Infection Measured by Reverse Transcriptase Polymerase-chain Reaction (RT-PCR)	Day 1 through the end of study (Day 359)
Number of Participants with Symptomatic SARS-CoV-2 Infection Measured by RT-PCR	Day 1 through the end of study (Day 359)

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2022
• Primary Completion (Actual): June 23, 2023
• Study Completion (Actual): June 23, 2023

Study Registration Dates

• First Submitted: February 19, 2022
• First Submitted That Met QC Criteria: February 19, 2022
• First Posted (Actual): February 22, 2022

Study Record Updates

• Last Update Posted (Actual): July 10, 2023
• Last Update Submitted That Met QC Criteria: July 6, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Coronavirus; COVID-19; SARS-CoV-2 Vaccine; Moderna; Messenger RNA; Omicron; COVID-19 Vaccine; mRNA-1273 vaccine; mRNA-1273; Spikevax; mRNA-1273.529; mRNA-1273.529 vaccine; Multivalent Vaccine; Variant Strains
• Other Study ID Numbers: mRNA-1273-P305; 2022-000063-51 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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