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

NCT05249829 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: mRNA-1273-P3052022-000063-51
• Study Type: interventional
• Target: 3,548
• Locations: 1 country
• Sites: 29

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.

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

Outcome Measures

Primary Outcomes (12)

• Part 1: Geometric Mean Concentration (GMC) of mRNA-1273.529 and mRNA-1273 Against the B.1.1.529 Strain at Day 29

  Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. Results are reported as absorbance units/millilitre (AU/mL). The GMC 95% confidence interval (CI) was calculated based on the t-distribution of the log-transformed values then back-transformed to the original scale for presentation.

  Day 29 (post vaccination)

• Part 1: GMC of mRNA-1273.529 and mRNA-1273 Against the B.1.1.529 Strain at Day 85

  Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. Results are reported as AU/mL. The GMC 95% CI was calculated based on the t-distribution of the log-transformed values then back-transformed to the original scale for presentation.

  Day 85 (post vaccination)

• Part 2: GMC of mRNA-1273.214 and mRNA-1273 Against the B1.1.529 Strain at Day 29

  Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. Results are reported as AU/mL. The GMC 95% CI was calculated based on the t-distribution of the log-transformed values then back-transformed to the original scale for presentation.

  Day 29 (post vaccination)

• Part 2: GMC of mRNA-1273.214 and mRNA-1273 Against the B1.1.529 Strain at Day 85

  Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. Results are reported as AU/mL. The GMC 95% CI was calculated based on the t-distribution of the log-transformed values then back-transformed to the original scale for presentation.

  Day 85 (post vaccination)

• Part 2: GMC of mRNA-1273.214 and mRNA-1273 Against the Ancestral Strain at Day 29

  Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. The ancestral (prototype) strain was Wuhan-Hu-1. Results are reported as AU/mL. The GMC 95% CI was calculated based on the t-distribution of the log-transformed values then back-transformed to the original scale for presentation.

  Day 29 (post vaccination)

• Part 2: GMC of mRNA-1273.214 and mRNA-1273 Against the Ancestral Strain ay Day 85

  Blood samples for immunogenicity assessments were collected during protocol-specified study visits. The serum neutralizing antibody levels were measured by pseudovirus neutralization assays. The ancestral strain was Wuhan-Hu-1. Results are reported as AU/mL. The GMC 95% CI was calculated based on the t-distribution of the log-transformed values then back-transformed to the original scale for presentation.

  Day 85 (post vaccination)

• Parts 1 and 2: Percentage of Participants With Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs)

  Reactogenicity refers to the occurrence and intensity of selected signs and symptoms (ARs) occurring after vaccine injection. Participants recorded such occurrences in an electronic diary on the day of study vaccine injection and for the 7 days after the day of dosing. Solicited local ARs were injection site pain, injection site erythema (redness), injection site swelling/induration (hardness), and axillary (underarm) swelling or tenderness ipsilateral to the side of the injection. Solicited systemic ARs were headache, fatigue, myalgia (muscle aches all over the body), arthralgia (joint aches in several joints), nausea/vomiting, chills, and fever (oral temperature). The Investigator determined if a solicited AR was also to be recorded as an adverse event (AE). A summary of all Serious and Non Serious AEs, regardless of causality, is located in the 'Adverse Events' section.

  Up to Day 8 (7 days post-vaccination)

• Parts 1 and 2: Number of Participants With Unsolicited AEs

  An AE was any untoward medical occurrence associated with the use of a drug/vaccine, whether or not considered related to the drug/vaccine. An unsolicited AE was any AE reported by the participant that was not specified as a solicited AR in the protocol or was specified as a solicited AR but starts outside the protocol-defined period for reporting solicited ARs (that is, 7 days after vaccination). A summary of all Serious and Non Serious AEs, regardless of causality, is located in the 'Adverse Events' section.

  Up to Day 29 (28 days post-vaccination)

• Parts 1 and 2: Number of Participants With Serious AEs (SAEs)

  An AE was considered an SAE if, in the view of either the investigator or Sponsor, it resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization (hospitalization or prolongation of hospitalization in the absence of a precipitating event was not in itself an SAE), resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, was a congenital anomaly/birth defect, or was a medically important event. A summary of all Serious and Non Serious AEs, regardless of causality, is located in the 'Adverse Events' section.

  Day 1 to end of study (Day 359)

• Parts 1 and 2: Number of Participants With Medically Attended AEs (MAAEs)

  An MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner (HCP). This would include visits to a clinic for unscheduled assessments (for example, rash assessment, abnormal laboratory follow-up, coronavirus disease 2019 \[COVID-19\]) and visits to HCPs external to the clinic (for example, urgent care, primary care physician). A summary of all Serious and Non Serious AEs, regardless of causality, is located in the 'Adverse Events' section.

  Day 1 to end of study (Day 359)

• Parts 1 and 2: Number of Participants With AEs Leading to Withdrawal

  An AE leading to withdrawal was defined as any AE that caused the participant to withdraw from the study, regardless of whether the decision to withdraw from the study was made by the participant or by the Investigator. A summary of all Serious and Non Serious AEs, regardless of causality, is located in the 'Adverse Events' section.

  Day 1 to end of study (Day 359)

• Parts 1 and 2: Number of Participants With AEs of Special Interest (AESIs)

  An AESI is an AE (serious or non serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the investigator to the Sponsor was required. Such events may have required further investigation to characterize and understand them. A summary of all Serious and Non Serious AEs, regardless of causality, is located in the 'Adverse Events' section.

  Day 1 to end of study (Day 359)

Secondary Outcomes (9)

• Part 1: GMC of mRNA-1273.529 and mRNA-1273 Against the B.1.1.529 Strain at Day 29 and Day 85

  Day 29 and Day 85 (post vaccination)

• Part 1: GMC of mRNA-1273.529 and mRNA-1273 Against the B.1.1.529 Strain at Day 179

  Day 179 (post vaccination)

• Part 1: GMC of mRNA-1273.529 and mRNA-1273 Against the Ancestral Strain at Day 29, Day 85, and Day 179

  Day 29, Day 85, Day 179 (post vaccination)

• Parts 1 and 2: Percentage of Participants With Seroresponse Against SARS-CoV-2

  Days 29, 85, 179, and 359

• Part 2: GMC of mRNA-1273.214 and mRNA-1273 Against Other Variant Strains

  Days 29 and 85

Study Arms (4)

Part 1: mRNA-1273.529

EXPERIMENTAL

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

Part 1: mRNA-1273

ACTIVE COMPARATOR

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

Part 2: mRNA-1273.214

EXPERIMENTAL

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

Part 2: mRNA-1273

ACTIVE COMPARATOR

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

Interventions

mRNA-1273.529 BIOLOGICAL

Sterile liquid for injection

Part 1: mRNA-1273.529

mRNA-1273 BIOLOGICAL

Sterile liquid for injection

Part 1: mRNA-1273; Part 2: mRNA-1273

mRNA-1273.214 BIOLOGICAL

Sterile liquid for injection

Part 2: mRNA-1273.214

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• ModernaTX, Inc.: lead

Study Sites (29)

Aberdeen Royal Infirmary - PPDS

Aberdeen, Aberdeenshire, AB25 2ZD, United Kingdom

Location

Southmead Hospital

Bristol, Avon, BS10 5NB, United Kingdom

Location

Wansford and Kingscliffe Practice

Wansford, Cambridgeshire, PE8 6PL, United Kingdom

Location

Halton General Hospital

Runcorn, Cheshire, WA7 2DA, United Kingdom

Location

The James Cook University Hospital

Middlesbrough, Cleveland, TS4 3BW, United Kingdom

Location

Royal Cornwall Hospital

Truro, Cornwall, TR1 3LJ, United Kingdom

Location

Royal Devon and Exeter Hospital NHS Trust

Exeter, Devon, EX2 5DW, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, Dorset, BH7 7DW, United Kingdom

Location

Gloucester Royal Hospital

Gloucester, Gloucestershire, GL1 3NN, United Kingdom

Location

Portsmouth Research Hub

Portsmouth, Hampshire, PO1 3HN, United Kingdom

Location

Fylde Coast Clinical Research

Blackpool, Lancashire, FY3 7EN, United Kingdom

Location

Leicester General Hospital

Leicester, Leicestershire, LE5 4PW, United Kingdom

Location

Salford Royal Hospital - PPDS

Salford, Manchester, United Kingdom

Location

University College London Hospitals Covid-19 Vaccine Centre

London, Middlesex, WC1E 6EB, United Kingdom

Location

Castle Hill Hospital

Hull, North Humberside, HU16 5JQ, United Kingdom

Location

The Princess Royal Hospital

Telford, Shropshire, TF1 6TF, United Kingdom

Location

Royal United Hospital

Bath, Somerset, BA1 3NG, United Kingdom

Location

Sheffield/Northern General Hospital

Sheffield, South Yorkshire, S5 7AU, United Kingdom

Location

Royal Glamorgan Hospital - PPDS

Pont-y-clun, Wales, CF72 8XR, United Kingdom

Location

Bradford Institute for Health Research

Bradford, West Yorkshire, BD9 6RJ, United Kingdom

Location

Great Western Hospital

Swindon, Wiltshire, SN3 6BB, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, B15 2TH, United Kingdom

Location

Barts Hospital

London, EC1A 7BE, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Chelsea and Westminster Hospital

London, SW10 9NH, United Kingdom

Location

St. George's Hospital

London, SW17 0RE, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Related Publications (1)

• Lee IT, Cosgrove CA, Moore P, Bethune C, Nally R, Bula M, Kalra PA, Clark R, Dargan PI, Boffito M, Sheridan R, Moran E, Darton TC, Burns F, Saralaya D, Duncan CJA, Lillie PJ, San Francisco Ramos A, Galiza EP, Heath PT, Girard B, Parker C, Rust D, Mehta S, de Windt E, Sutherland A, Tomassini JE, Dutko FJ, Chalkias S, Deng W, Chen X, Feng J, Tracy L, Zhou H, Miller JM, Das R; Study Investigators. Omicron BA.1-containing mRNA-1273 boosters compared with the original COVID-19 vaccine in the UK: a randomised, observer-blind, active-controlled trial. Lancet Infect Dis. 2023 Sep;23(9):1007-1019. doi: 10.1016/S1473-3099(23)00295-5. Epub 2023 Jun 19.

  PMID: 37348519 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; COVID-19

Interventions

2019-nCoV Vaccine mRNA-1273; mRNA-1273.214 COVID-19 vaccine

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors

Results Point of Contact

• Title: Moderna Clinical Trials Support Center
• Organization: ModernaTX, Inc.

clinicaltrials@modernatx.com

1-877-777-7187

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase A of this study will be observer-blinded. Phase B of the study will be open-label and blinding is not applicable

Study Record Dates

• First Submitted: February 19, 2022
• First Posted: February 22, 2022
• Study Start: February 16, 2022
• Primary Completion: June 23, 2023
• Study Completion: June 23, 2023
• Last Updated: August 9, 2024
• Results First Posted: August 9, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (29)