Clinical trial NCT05249829: A Study to Evaluate the Immunogenicity and Safety of Omicron Variant Vaccines in Comparison With mRNA-1273 Booster Vaccine for COVID-19
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: SARS-CoV-2
Keywords: Spikevax
mRNA-1273
mRNA-1273 vaccine
mRNA-1273.529
mRNA-1273.529 vaccine
Omicron
SARS-CoV-2
SARS-CoV-2 Vaccine
Coronavirus
Messenger RNA
COVID-19
COVID-19 Vaccine
Moderna
Multivalent Vaccine
Variant Strains
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-22
Enrollment: 3548
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase A of this study will be observer-blinded. Phase B of the study will be open-label and blinding is not applicable
Primary purpose: PREVENTION

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Geometric Mean Concentration (GMC) of mRNA-1273.529 and mRNA-1273 Against the B.1.1.529 Strain at Day 29
timeFrame: Day 29 (post vaccination)
measure: Part 1: GMC of mRNA-1273.529 and mRNA-1273 Against the B.1.1.529 Strain at Day 85
timeFrame: Day 85 (post vaccination)
measure: Part 2: GMC of mRNA-1273.214 and mRNA-1273 Against the B1.1.529 Strain at Day 29
timeFrame: Day 29 (post vaccination)
measure: Part 2: GMC of mRNA-1273.214 and mRNA-1273 Against the B1.1.529 Strain at Day 85
timeFrame: Day 85 (post vaccination)
measure: Part 2: GMC of mRNA-1273.214 and mRNA-1273 Against the Ancestral Strain at Day 29
timeFrame: Day 29 (post vaccination)
measure: Part 2: GMC of mRNA-1273.214 and mRNA-1273 Against the Ancestral Strain ay Day 85
timeFrame: Day 85 (post vaccination)
measure: Parts 1 and 2: Percentage of Participants With Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs)
timeFrame: Up to Day 8 (7 days post-vaccination)
measure: Parts 1 and 2: Number of Participants With Unsolicited AEs
timeFrame: Up to Day 29 (28 days post-vaccination)
measure: Parts 1 and 2: Number of Participants With Serious AEs (SAEs)
timeFrame: Day 1 to end of study (Day 359)
measure: Parts 1 and 2: Number of Participants With Medically Attended AEs (MAAEs)
timeFrame: Day 1 to end of study (Day 359)
measure: Parts 1 and 2: Number of Participants With AEs Leading to Withdrawal
timeFrame: Day 1 to end of study (Day 359)
measure: Parts 1 and 2: Number of Participants With AEs of Special Interest (AESIs)
timeFrame: Day 1 to end of study (Day 359)
Secondary outcomes:
measure: Part 1: GMC of mRNA-1273.529 and mRNA-1273 Against the B.1.1.529 Strain at Day 29 and Day 85
timeFrame: Day 29 and Day 85 (post vaccination)
measure: Part 1: GMC of mRNA-1273.529 and mRNA-1273 Against the B.1.1.529 Strain at Day 179
timeFrame: Day 179 (post vaccination)
measure: Part 1: GMC of mRNA-1273.529 and mRNA-1273 Against the Ancestral Strain at Day 29, Day 85, and Day 179
timeFrame: Day 29, Day 85, Day 179 (post vaccination)
measure: Parts 1 and 2: Percentage of Participants With Seroresponse Against SARS-CoV-2
timeFrame: Days 29, 85, 179, and 359
measure: Part 2: GMC of mRNA-1273.214 and mRNA-1273 Against Other Variant Strains
timeFrame: Days 29 and 85
measure: Part 2: Percentage of Participants With Asymptomatic SARS-CoV-2 Infection Measured by Reverse Transcriptase Polymerase-chain Reaction (RT-PCR)
timeFrame: Day 14 through the end of study (Day 359)
measure: Part 2: Percentage of Participants With Symptomatic SARS-CoV-2 Infection Measured by RT-PCR
timeFrame: Day 1 through the end of study (Day 359)
measure: Part 2: Percentage of Participants With Primary Case Definition of COVID-19
timeFrame: Day 14 through the end of study (Day 359)
measure: Part 2: Percentage of Participants With Secondary Case Definition of COVID-19
timeFrame: Day 14 through the end of study (Day 359)
Other outcomes:
Locations:
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary - PPDS
state: Aberdeenshire
city: Bristol
country: United Kingdom
facility: Southmead Hospital
state: Avon
city: Wansford
country: United Kingdom
facility: Wansford and Kingscliffe Practice
state: Cambridgeshire
city: Runcorn
country: United Kingdom
facility: Halton General Hospital
state: Cheshire
city: Middlesbrough
country: United Kingdom
facility: The James Cook University Hospital
state: Cleveland
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
state: Cornwall
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital NHS Trust
state: Devon
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: Dorset
city: Gloucester
country: United Kingdom
facility: Gloucester Royal Hospital
state: Gloucestershire
city: Portsmouth
country: United Kingdom
facility: Portsmouth Research Hub
state: Hampshire
city: Blackpool
country: United Kingdom
facility: Fylde Coast Clinical Research
state: Lancashire
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
state: Leicestershire
city: Salford
country: United Kingdom
facility: Salford Royal Hospital - PPDS
state: Manchester
city: London
country: United Kingdom
facility: University College London Hospitals Covid-19 Vaccine Centre
state: Middlesex
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
state: North Humberside
city: Telford
country: United Kingdom
facility: The Princess Royal Hospital
state: Shropshire
city: Bath
country: United Kingdom
facility: Royal United Hospital
state: Somerset
city: Sheffield
country: United Kingdom
facility: Sheffield/Northern General Hospital
state: South Yorkshire
city: Pontyclun
country: United Kingdom
facility: Royal Glamorgan Hospital - PPDS
state: Wales
city: Bradford
country: United Kingdom
facility: Bradford Institute for Health Research
state: West Yorkshire
city: Swindon
country: United Kingdom
facility: Great Western Hospital
state: Wiltshire
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: London
country: United Kingdom
facility: Barts Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Kings College Hospital
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital
city: London
country: United Kingdom
facility: St. George's Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
Study officials:
References: