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AzTrials

COVID-19Phase 3NCT05543356

COVID-19 Fourth Dose Study in Australia

A Phase 3 study testing Tozinameran, Elasomeran and Bivalent Pfizer-BioNTech in people with COVID-19, run by Murdoch Childrens Research Institute at 1 site in Australia.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This clinical trial will be a blinded, randomised study to determine the safety, reactogenicity, and immunogenicity of a second booster dose of SARS-CoV-2 vaccines in adults enrolled over two consecutive stages. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
COVID-19
What is being tested?
Tozinameran, Elasomeran and Bivalent Pfizer-BioNTech
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteAustralia
Study dates
2 May 2022to 30 Nov 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Have completed a primary schedule of two doses of Pfizer-BioNTech or AstraZeneca vaccines and received a booster of Pfizer-BioNTech vaccine (30µg) at least 3 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Australia1 site

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

    Melbourne, Victoria, 3052

Other trials in Australia

About this study

Official title: A Randomised Controlled Trial to Assess the Immunogenicity, Safety and Reactogenicity of a Second Standard Monovalent (Ancestral) or Bivalent Omicron-specific COVID-19 Vaccine Booster Dose (Pfizer-BioNTech or Moderna) in Healthy Adults in Australia.

This clinical trial will be a blinded, randomised study to determine the safety, reactogenicity, and immunogenicity of a second booster dose of SARS-CoV-2 vaccines in adults enrolled over two consecutive stages. Stage 1 will commence at the time of study approval and transition to stage 2 once bivalent vaccines are approved and available in Australia.

Read the detailed description

Participants will be adults aged 18 years or older who have been previously primed with two doses of either Pfizer-BioNTech (BNT162b2, or Comirnaty®) or AstraZeneca (ChAdOx1-S, or Vaxzevria®) and boosted at least 3 months earlier with Pfizer BioNTech vaccine (30µg). There will be no upper age limit. Participants will be recruited from the Murdoch Children's Research Institute, the Royal Children's Hospital (RCH), the Peter Doherty Research Institute, and, if necessary, the greater Melbourne area. Ideally, 100 participants will be recruited per group unless bivalent Omicron-specific vaccines are introduced before this target is reached for monovalent ancestral vaccines. There will be 800 participants in total. Procedures will be implemented to ensure participants of all ages (aged 18 and above) are included and that there is an even age distribution in each group (<50 and ≥50 years).

Conditions
COVID-19
Being tested
Tozinameran, Elasomeran, Bivalent Pfizer-BioNTech, Bivalent Moderna
Keywords
Booster dose Moderna and Pfizer, mRNA vaccine, monovalent, bivalent
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TozinameranBiological

    Also called BNT162b2, Pfizer-BioNTech, Comirnaty

    A single standard dose (30mcg) will be administered on day 0 of the study.

  • ElasomeranBiological

    Also called mRNA-1273, Spikevax, Moderna

    A single standard dose (50mcg) of the intervention will be administered on day 0 of the study.

  • TozinameranBiological

    Also called BNT162b2, Pfizer-BioNTech, Comirnaty

    A single standard dose (30mcg) will be administered on day 0 of the study.

  • ElasomeranBiological

    Also called mRNA-1273, Spikevax, Moderna

    A single standard dose (50mcg) of the intervention will be administered on day 0 of the study.

  • Bivalent Pfizer-BioNTechBiological

    Also called BNT162b2 + BNT162b2 OMI

    A single standard dose (BNT162b2 15μg +BNT162b2 OMI 15μg) will be administered on day 0 of the study.

  • Bivalent ModernaBiological

    Also called mRNA-1273.214 +B.1.1.529 OMI

    A single standard dose (BNT162b2 15μg + BNT162b2 OMI 15μg)will be administered on day 0 of the study.

  • Bivalent Pfizer-BioNTechBiological

    Also called BNT162b2 + BNT162b2 OMI

    A single standard dose (BNT162b2 15μg + BNT162b2 OMI 15μg) will be administered on day 0 of the study.

  • Bivalent ModernaBiological

    Also called mRNA-1273.214 +B.1.1.529 OMI

    A single standard dose (BNT162b2 15μg +BNT162b2 OMI 15μg) will be administered on day 0 of the study.

Study groups in NCT05543356
Study groupRoleWhat they receive
Monovalent Pfizer-BioNTech(BNT162b2): Pfizer-BioNTech(BNT162b2)-Pfizer-BioNTech(BNT162b2)Active comparatorParticipants who received Pfizer-BioNTech(BNT162b2) as primary series and Pfizer-BioNTech(BNT162b2) as first booster will receive a second booster dose of: Biological/Vaccine: Tozinameran - Monovalent Tozinamrean is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Receives: Biological: Tozinameran
Monovalent Moderna(mRNA-1273, Spikevax®): Pfizer-BioNTech(BNT162b2)-Pfizer-BioNTech(BNT162b2)Active comparatorParticipants who received Pfizer-BioNTech(BNT162b2) as primary series and Pfizer-BioNTech(BNT162b2) as first booster will receive a second booster dose of: Biological/Vaccine: Elasomeran - Monovalent Elasomeran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2).
Receives: Biological: Elasomeran
Monovalent Pfizer-BioNTech(BNT162b2): AstraZeneca(ChAdOx1, Vaxzevria®)-Pfizer-BioNTech(BNT162b2)Active comparatorParticipants who received AstraZeneca (ChAdOx1, or Vaxzevria®) as primary series and Pfizer-BioNTech (BNT162b2) as first booster will received a second booster dose of: Biological/Vaccine: Tozinameran - Monovalent Tozinamrean is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Receives: Biological: Tozinameran
Monovalent Moderna(mRNA-1273, Spikevax®):AstraZeneca(ChAdOx1, Vaxzevria®)-Pfizer-BioNTech(BNT162b2)Active comparatorParticipants who received AstraZeneca (ChAdOx1, or Vaxzevria®) as primary series and Pfizer-BioNTech (BNT162b2) as first booster will received a second booster dose of: Biological/Vaccine: Elasomeran - Monovalent Elasomeran is a single-stranded, 5'-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2).
Receives: Biological: Elasomeran
Bivalent Pfizer-BioNTech (BNT162b2 OMI): Pfizer-BioNTech(BNT162b2)-Pfizer-BioNTech(BNT162b2)Active comparatorParticipants who received Pfizer-BioNTech(BNT162b2) as primary series and Pfizer-BioNTech(BNT162b2) as first booster will receive a second booster dose of: Biological/Vaccine: Pfizer-BioNTech, BNT162b2 OMI - bivalent Pfizer-BioNTech bivalent COVID-19 vaccine contains ancestral BNT162b2 and Omicron variant BNT162b2 Omi (BA.1). The Pfizer-BioNTech COVID-19 vaccine, BNT162b2, encodes a P2 mutant spike protein and is formulated as an RNA-lipid nanoparticle (LNP) of nucleoside-modified mRNA (modRNA).
Receives: Biological: Bivalent Pfizer-BioNTech
Bivalent Moderna (mRNA-1273.214): Pfizer-BioNTech(BNT162b2)-Pfizer-BioNTech(BNT162b2)Active comparatorParticipants who received Pfizer-BioNTech(BNT162b2) as primary series and Pfizer-BioNTech(BNT162b2) as first booster will receive a second booster dose of: Biological/Vaccine: Moderna, mRNA-1273.214 - bivalent The Moderna bivalent vaccine (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]).
Receives: Biological: Bivalent Moderna
Bivalent Pfizer-BioNTech (BNT162b2): AstraZeneca(ChAdOx1, Vaxzevria®)-Pfizer-BioNTech(BNT162b2)Active comparatorParticipants who received AstraZeneca (ChAdOx1-S, or Vaxzevria®) as primary series and Pfizer-BioNTech (BNT162b2) as first booster will received a second booster dose of: Biological/Vaccine: Pfizer-BioNTech, BNT162b2 OMI - bivalent Pfizer-BioNTech bivalent COVID-19 vaccine contains ancestral BNT162b2 and Omicron variant BNT162b2 Omi (BA.1). The Pfizer-BioNTech COVID-19 vaccine, BNT162b2, encodes a P2 mutant spike protein and is formulated as an RNA-lipid nanoparticle of nucleoside-modified mRNA.
Receives: Biological: Bivalent Pfizer-BioNTech
Bivalent Moderna (mRNA-1273.214): AstraZeneca(ChAdOx1, Vaxzevria®)-Pfizer-BioNTech(BNT162b2)Active comparatorParticipants who received AstraZeneca (ChAdOx1-S, or Vaxzevria®) as primary series and Pfizer-BioNTech (BNT162b2) as first booster will received a second booster dose of: Biological/Vaccine: Moderna, mRNA-1273.214 - bivalent The Moderna bivalent vaccine (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]).
Receives: Biological: Bivalent Moderna

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. SARS-CoV-2 specific Immunoglobulin (Ig)G antibodies at 28-days post booster vaccination

    Serum samples collected at 28-days post booster vaccination from all 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

    Measured: 28-days post booster vaccination

  2. 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.

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

Secondary outcomes (10)

  1. SARS-CoV-2 specific IgG antibodies at baseline (pre booster), and 6-months post booster vaccination

    Serum samples collected at baseline (pre booster), and 6-months post booster vaccination from all 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

    Measured: Baseline (pre booster), and 6-months post booster vaccination

  2. SARS-CoV-2 specific neutralising antibodies at baseline (pre booster), 28 days and 6-months post booster vaccination measured by surrogate virus neutralization test (sVNT)

    Serum samples collected at baseline (pre booster), 28 days- and 6-months post booster vaccination from all groups will be evaluated for SARS-CoV-2 specific neutralising antibodies using the GenScript® cPass surrogate virus neutralization test (sVNT) for both wild-type and Omicron variant. Neutralising antibody response will be reported as percentage (%) inhibition of receptor binding domain-angiotensin-converting enzyme 2 (RBD-ACE2) binding relative to a positive control.

    Measured: Baseline (pre booster), 28 days and 6 months post booster vaccination

  3. SARS-CoV-2 specific neutralising antibodies at baseline (pre booster), 28 days and 6- months post booster vaccination measured by SARS-CoV-2 microneutralisation assay

    A subset of samples 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.

    Measured: Baseline (pre booster), 28 days-, and 6-months post booster vaccination

  4. Interferon gamma (IFNγ) concentrations in International Units (IU)/mL

    Interferon gamma (IFNγ) concentrations as a measurement of cellular immunity will be assessed on a subset (40%) of the participants from each group. QuantiFERON Human IFN-γ SARS-CoV-2 (Qiagen) will be used to stimulate IFN-γ production in peripheral blood mononuclear cells (PBMCs) and then IFN-γ production will be measured using ELISA. Data will be presented as geometric mean concentration (GMC) and 95% confidence intervals (CI).

    Measured: Baseline (pre booster), 28 days-, and 6-months post booster vaccination

  5. Number of IFNγ producing cells/million PBMCs

    IFNγ producing cells as a measurement of cellular immunity will be assessed on a subset (40%) of the participants from each group. IFN-γ Enzyme-Linked ImmunoSpot (Elispot) assay will be performed on isolated peripheral blood mononuclear cells (PBMCs). Data will be reported as number of IFNγ producing cells/million and presented using means and 95% confidence intervals.

    Measured: Baseline (pre booster), 28 days-, and 6-months post booster vaccination

  6. Frequency of cytokine-expressing T cells

    Frequency of cytokine-expressing T cells will be assessed on a subset (40%) of participants using Flow cytometry (intracellular staining) on PBMCs samples. Data will be reported as frequency (%) of cytokine-expressing T cells presented as means and 95% CI.

    Measured: Baseline (pre booster), 28 days-, and 6-months post booster vaccination

  7. Cytokine concentrations following PBMCs stimulation

    Cytokine concentrations following PBMCs stimulation will be assessed on a subset (40%) of participants using multiplex cytokine assays.Data will be reported as cytokine concentrations in pg/ml and presented as GMC and 95% CI.

    Measured: Baseline (pre booster), 28 days and 6-months post booster vaccination

  8. Incidence of unsolicited adverse events (AE)

    All unsolicited AE will be collected for 28 days post booster vaccination. Data will be presented as proportion of participants who report unsolicited AE.

    Measured: 28 days-post booster vaccination

  9. Incidence of medically attended adverse events (AE)

    Participants with medically attended AE will be collected for 3 months post booster vaccination. Data will be presented as proportion of participants who report unsolicited AE.

    Measured: 3 months post booster vaccination

  10. Incidence of serious adverse events (SAE)

    SAE will be collected throughout the follow-up period of 6 months post booster vaccination. Data will be presented as a proportion of participants who report unsolicited SAE.

    Measured: 6 months post booster vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Sep 2022
  2. Study start2 May 2022
  3. Primary completion25 Jul 2022
  4. Study completion30 Nov 2022

Why it stopped: Withdrawal of supply of vaccine from one manufacturer

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Study participants who have received two doses of either Pfizer or Astrazena vaccine as their primary vaccine and a standard dose of Pfizer for their booster will be randomised into one of four groups. The four groups consist of a standard dose of either the monovalent or bivalent Pfizer or Moderna vaccine.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05543356
Sponsor's protocol ID
88825
Status last verified
Mar 2024
First submitted
14 Sep 2022
Last updated
15 Mar 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: We will share de-identified data to ethically approved studies in cases where participants have indicated on the consent form that they consent to the use of their data and where consistent with terms of collaboration agreements.

Publications

  • Mazarakis N, Toh ZQ, Neal E, Bright K, Luu S, Quah L, Ng YY, Nguyen C, Hart J, Do LAH, Rudel A, Dassanayake S, Higgins RA, Ong DS, Justice F, Moore KA, Watts E, Mahanty S, Subbarao K, Mulholland K, von Mollendorf C, Licciardi PV. The immunogenicity, reactogenicity, and safety of a bivalent mRNA or protein COVID-19 vaccine given as a fourth dose. J Infect. 2025 Mar;90(3):106447. doi: 10.1016/j.jinf.2025.106447. Epub 2025 Feb 18.

    PubMed 39978439

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tozinameran, Elasomeran and Bivalent Pfizer-BioNTech in people with COVID-19, run by Murdoch Childrens Research Institute at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 15 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

SARS-CoV-2 specific Immunoglobulin (Ig)G antibodies at 28-days post booster vaccination (time frame: 28-days post booster vaccination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05543356, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2024.

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