COVID-19 Booster Study in Healthy Adults in Australia

NCT05658523 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 1 other identifier: 91108
• Study Type: interventional
• Target: 496
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double-blinded, randomised study to determine the safety, reactogenicity, and immunogenicity of a bivalent mRNA Moderna COVID-19 vaccine or a protein-based Novavax COVID-19 vaccine given as a fourth dose in healthy adults in Australia.

Conditions

COVID-19

Keywords

Booster dose Moderna and Novavax; control group; monovalent, bivalent

Outcome Measures

Primary Outcomes (2)

• SARS-CoV-2 Specific Immunoglobulin (Ig)G Antibodies at 28-days Post Booster Vaccination

  Serum samples collected at 28-days post booster vaccination from the two intervention groups will be evaluated for SARS-CoV-2 specific IgG antibodies using the commercial Euroimmun S1 IgG ELISA. Data will be reported as binding antibody units/mL and presented as geometric mean concentration and 95% confidence intervals

  28-days post booster vaccination

• Total Incidence of Solicited Reactions (Systemic and Local)

  Questionnaire to document solicited reactions is developed specifically for this study. Data will be reported as the proportion of participants who report by each intervention arm. Solicited reactions such as pain, tenderness, erythema/redness, induration/swelling, fever, nausea/vomiting, headache, fatigue/malaise, myalgia, arthralgia will be collected from the participants 7 days post-vaccination. Reactogenicity was graded on a 0-4 scale: Grade 0 = no symptom; Grade 1 = mild and does not interfere with activity; Grade 2 = moderate or requiring repeated non-narcotic analgesia; Grade 3 = severe, limiting or preventing daily activity; Grade 4 = potentially life-threatening, requiring ER visit or hospitalisation.

  Total incidence of solicited reactions will be measured for 7 days post booster vaccination

Secondary Outcomes (10)

• SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 and 18 Months Post Booster Vaccination

  Baseline (pre booster), 6-months,12-months and 18-months post booster vaccination

• SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT)

  Baseline (pre booster), 28 days, 6,12, 18, 24, and 30 months post booster vaccination

• SARS-CoV-2 Specific Neutralising Antibodies at Baseline (Pre Booster), 28 Days and 6, 12 and 18 Months Post Booster Vaccination Measured by SARS-CoV-2 Microneutralisation Assay

  Baseline (pre booster), 6,12 and 18-months post booster vaccination

• Interferon Gamma (IFNγ) Concentrations in International Units (IU)/mL

  Baseline (pre booster), Day 28, 6-months and 12-months post booster vaccination

• Number of IFNγ Producing Cells/Million PBMCs

  Baseline (pre booster), 6, 12 and 18-months post booster vaccination

Other Outcomes (1)

• SARS-CoV-2 Infections

  24 months post booster vaccination

Study Arms (3)

Bivalent Moderna (mRNA-1273.214)

ACTIVE COMPARATOR

Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of bivalent mRNA Moderna COVID-19 vaccine (mRNA-1273.214) The mRNA-1273.214 encodes the prefusion stabilized S protein of SARS-CoV-2 formulated in RNA-lipid nanoparticles composed of 4 lipids and 1-monomethoxypolyethyleneglycol-2, 3-dimyristylglycerol with polyethylene glycol. 25μg of each mRNA sequence that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]).

Biological: Bivalent Moderna

Novavax

ACTIVE COMPARATOR

Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will receive a booster dose of Novavax COVID-19 protein subunit vaccine. Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms).

Biological: Novavax

Control group- no vaccine

NO INTERVENTION

Participants who have received three doses of COVID-19 vaccine, with the last dose at least 6 months prior to the study, will be recruited but will not receive any COVID-19 vaccine.

Interventions

Bivalent Moderna BIOLOGICAL

A single standard dose of the bivalent Moderna (mRNA-1273.214) COVID-19 vaccine containing equal amounts of mRNAs (25μg of each mRNA sequence) that encode the prefusion stabilized spike glycoproteins of the ancestral SARS-CoV-2 (Wuhan-Hu-1) and the Omicron variant (B.1.1.529 \[BA.1\]) with mRNAs encapsulated in lipid nanoparticles, will be administered on day 0 of the study.

Also known as: mRNA-1273.214

Bivalent Moderna (mRNA-1273.214)

Novavax BIOLOGICAL

A single dose of Novavax contains 5μg of SARS-CoV-2 spike protein and is adjuvanted with Matrix-M. Adjuvant Matrix-M contains, per 0.5 mL dose: Quillaja saponaria saponins fraction A (42.5 micrograms) and Quillaja saponaria saponins fraction C (7.5 micrograms), will be administered on day 0 of the study.

Novavax

Eligibility Criteria

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

You may qualify if:

• Have received three doses of COVID-19 vaccines at least 6 months earlier.
• No confirmed SARS-CoV-2 infection on PCR or RAT within the last 3 months.
• Willing and able to give written informed consent.
• Aged 18 years or above.
• Willing to complete the follow-up requirements of the study.

You may not qualify if:

• Currently receiving immunosuppressive medication or anti-cancer chemotherapy.
• Known HIV infection.
• Congenital immune deficiency syndrome.
• Received immunoglobulin or other blood products in the three months prior to potential study booster vaccination.
• Study staff and their relatives.
• Have a history of a severe allergic reaction to any COVID-19 vaccines or have a medical exemption to receiving further COVID-19 vaccines.
• Cannot read or understand English.

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead
• Coalition for Epidemic Preparedness Innovations: collaborator
• The Peter Doherty Institute for Infection and Immunity: collaborator

Study Sites (1)

Royal Children's Hospital, Murdoch Children's Research Institute

Melbourne, Victoria, 3052, Australia

Location

Related Links

• Coalition for Epidemic Preparedness Innovations (CEPI). Priority List of Adverse Events of Special Interest: COVID-19 2020 \[Available from:
• World Health Organization. Interim statement on the use of additional booster doses of Emergency Use Listed mRNA vaccines against COVID-19 2022
• US Food and Drug Administration (FDA). Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials 2007
• International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Addendum on Estimands and Sensitivity Analysis in Clinical Trials to the Guideline on Statistical Principles for Clinical Trials 2019

MeSH Terms

Conditions

COVID-19

Interventions

2019-nCoV Vaccine mRNA-1273; mRNA-1273.214 COVID-19 vaccine; NVX-CoV2373 adjuvated lipid nanoparticle

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus 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: Kathryn Bright
• Organization: Murdoch Childrens Research Institute

kathryn.bright@mcri.edu.au

+61 3 99366656

Study Officials

• Kim Mulholland, MD/Prof

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The participants and those evaluating reactogenicity will be blinded to the vaccine allocation for the first 7 days following vaccination. After that, both clinical investigators and participants will be aware of their investigational product. Laboratory staff will remain blinded to the investigational product.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Study participants who have previously received 3 COVID-19 vaccines will be either randomised into one of two vaccine groups or be part of a self-selected control group. Randomised participants will receive a standard dose of either the bivalent Moderna or the protein-based Novavax vaccine. 200 non-randomised participants will be part of a control group and will not receive any COVID-19 vaccine.

Study Record Dates

• First Submitted: December 19, 2022
• First Posted: December 20, 2022
• Study Start: February 28, 2023
• Primary Completion: October 13, 2024
• Study Completion: April 1, 2026
• Last Updated: January 2, 2026
• Results First Posted: January 2, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Individual participant data (IPD) sharing plans in development
• Access Criteria: In development

Locations

AU (1)