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NCT Number: NCT05658523

COVID-19 Booster Study in Healthy Adults in Australia

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

COVID-19 Coronaviridae Infections Coronavirus Infections Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

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

Melbourne, Victoria, 3052, Australia

About this study

This is a blinded, two-arm randomised study to determine the safety, reactogenicity and immunogenicity of a fourth dose of SARS-CoV-2 vaccines in Australia in adults 18 years or older who have received their third dose of COVID-19 vaccine at least six months previously. Participants will be randomised to receive either bivalent Moderna (mRNA-1273.214) or Novavax. A separate non-randomised control arm (no vaccine given), frequency matched by age to the vaccine groups will also be enrolled for comparison. A total of 200 participants per group will be recruited.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

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.

Other names: 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.

Primary outcomes

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

    Time frame: 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

  2. Total Incidence of Solicited Reactions (Systemic and Local)

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

    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.

Secondary outcomes

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

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

    Serum samples collected at baseline (pre booster), 28 days, 6,12, 18, 24, and 30 months post booster vaccination from the two intervention groups and the control group 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

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

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

    Neutralising antibody levels will be measured using the GenScript® cPass sVNT, which reports inhibition relative to a positive control. Results are expressed as concentrations (U/mL) and summarised as geometric mean concentrations (GMCs) with 95% CIs.

  3. 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

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

    A subset of samples (20%) from all timepoints will be assessed using a SARS-CoV-2 microneutralisation assay to both the wild type (vaccine) strain and for two SARS-CoV-2 Variants of concern. Neutralizing antibody will be reported as endpoint titre.

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

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

    Interferon gamma (IFNγ) concentrations as a measurement of cellular immunity will be assessed on a subset (50%) of the participants from each group. QuantiFERON Human IFN-γ SARS-CoV-2 (Qiagen) will be used to stimulate IFN-γ production in whole blood and then IFN-γ production will be measured using Enzyme-Linked ImmunoSorbent Assay (ELISA). Data will be presented as geometric mean concentration (GMC) and 95% confidence intervals (CI).

  5. Number of IFNγ Producing Cells/Million PBMCs

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

    IFNγ producing cells as a measurement of cellular immunity will be assessed on a subset (50%) of the participants from each group. IFN-γ Enzyme-Linked ImmunoSpot (Elispot) assay will be performed on isolated peripheral blood mononuclear cells (PBMCs) stimulated with SARS-CoV-2 specific peptides. Data will be reported as number of IFNγ producing cells/million and presented using means and 95% confidence intervals.

  6. Frequency of Cytokine-expressing T Cells

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

    Frequency of cytokine-expressing T cells will be assessed on a subset (50%) of participants using Flow cytometry (intracellular staining) on PBMCs samples stimulated with SARS-CoV-2 specific peptides. Data will be reported as frequency (%) of cytokine-expressing T cells presented as means and 95% CI.

  7. Cytokine Concentrations Following PBMCs Stimulation

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

    Cytokine concentrations following PBMCs stimulation will be assessed on a subset (50%) of participants using multiplex cytokine assays. Data will be reported as cytokine concentrations in pg/ml and presented as GMC and 95% CI.

  8. Incidence of Unsolicited Adverse Events (AE)

    Time frame: 28 days-post booster vaccination

    Unsolicited adverse events were collected for 28 days post-booster. Results are reported as the number and percentage of randomised participants in each arm who experienced an unsolicited AE.

  9. Incidence of Medically Attended Adverse Events (AE)

    Time frame: 3 months post booster vaccination

    Participants with medically attended AE will be collected for 3 months post booster vaccination. Data will be presented as number of medically attended adverse events. Serious adverse events (SAEs) are reported separately.

  10. Incidence of Serious Adverse Events (SAE)

    Time frame: 24 months post booster vaccination

    Serious adverse events (SAEs) were collected throughout the 24-month follow-up period after booster vaccination. Data are reported as the number of SAEs occurring in each randomised arm.

Other outcomes

  1. SARS-CoV-2 Infections

    Time frame: 24 months post booster vaccination

    SARS-CoV-2 infections were recorded throughout the 24-month follow-up period based on participant self-report of a positive RAT or PCR test. Data are reported as the number of infections occurring in each study arm during this period

Sponsors and collaborators

Lead sponsor

Murdoch Childrens Research Institute

Other

Collaborators

  • Coalition for Epidemic Preparedness Innovations
  • The Peter Doherty Institute for Infection and Immunity

Registry information

Official study title

A Randomised Controlled Trial to Assess the Immunogenicity, Safety and Reactogenicity 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

Important dates

Study start
2023
Primary completion
2024
Study completion
2026
First posted
Dec 20, 2022
Registry last updated
Jan 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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