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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT05543356
Registration number
NCT05543356
Ethics application status
Date submitted
14/09/2022
Date registered
16/09/2022
Date last updated
15/03/2024
Titles & IDs
Public title
COVID-19 Fourth Dose Study in Australia
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Scientific 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.
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Secondary ID [1]
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88825
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
COVID-19
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Condition category
Condition code
Infection
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Other infectious diseases
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Respiratory
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Other respiratory disorders / diseases
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - Tozinameran
Other interventions - Elasomeran
Other interventions - Tozinameran
Other interventions - Elasomeran
Other interventions - Bivalent Pfizer-BioNTech
Other interventions - Bivalent Moderna
Other interventions - Bivalent Pfizer-BioNTech
Other interventions - Bivalent Moderna
Active Comparator: Monovalent Pfizer-BioNTech(BNT162b2): Pfizer-BioNTech(BNT162b2)-Pfizer-BioNTech(BNT162b2) - Participants 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).
Active Comparator: Monovalent Moderna(mRNA-1273, Spikevax®): Pfizer-BioNTech(BNT162b2)-Pfizer-BioNTech(BNT162b2) - Participants 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).
Active Comparator: Monovalent Pfizer-BioNTech(BNT162b2): AstraZeneca(ChAdOx1, Vaxzevria®)-Pfizer-BioNTech(BNT162b2) - Participants 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).
Active Comparator: Monovalent Moderna(mRNA-1273, Spikevax®):AstraZeneca(ChAdOx1, Vaxzevria®)-Pfizer-BioNTech(BNT162b2) - Participants 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).
Active Comparator: Bivalent Pfizer-BioNTech (BNT162b2 OMI): Pfizer-BioNTech(BNT162b2)-Pfizer-BioNTech(BNT162b2) - Participants 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).
Active Comparator: Bivalent Moderna (mRNA-1273.214): Pfizer-BioNTech(BNT162b2)-Pfizer-BioNTech(BNT162b2) - Participants 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]).
Active Comparator: Bivalent Pfizer-BioNTech (BNT162b2): AstraZeneca(ChAdOx1, Vaxzevria®)-Pfizer-BioNTech(BNT162b2) - Participants 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.
Active Comparator: Bivalent Moderna (mRNA-1273.214): AstraZeneca(ChAdOx1, Vaxzevria®)-Pfizer-BioNTech(BNT162b2) - Participants 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]).
Other interventions: Tozinameran
A single standard dose (30mcg) will be administered on day 0 of the study.
Other interventions: Elasomeran
A single standard dose (50mcg) of the intervention will be administered on day 0 of the study.
Other interventions: Tozinameran
A single standard dose (30mcg) will be administered on day 0 of the study.
Other interventions: Elasomeran
A single standard dose (50mcg) of the intervention will be administered on day 0 of the study.
Other interventions: Bivalent Pfizer-BioNTech
A single standard dose (BNT162b2 15µg +BNT162b2 OMI 15µg) will be administered on day 0 of the study.
Other interventions: Bivalent Moderna
A single standard dose (BNT162b2 15µg + BNT162b2 OMI 15µg)will be administered on day 0 of the study.
Other interventions: Bivalent Pfizer-BioNTech
A single standard dose (BNT162b2 15µg + BNT162b2 OMI 15µg) will be administered on day 0 of the study.
Other interventions: Bivalent Moderna
A single standard dose (BNT162b2 15µg +BNT162b2 OMI 15µg) will be administered on day 0 of the study.
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Intervention code [1]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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SARS-CoV-2 specific Immunoglobulin (Ig)G antibodies at 28-days post booster vaccination
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Assessment method [1]
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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
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Timepoint [1]
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28-days post booster vaccination
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Primary outcome [2]
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Total incidence of solicited reactions (systemic and local)
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Assessment method [2]
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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.
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Timepoint [2]
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Total incidence of solicited reactions will be measured for 7 days post booster vaccination
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Secondary outcome [1]
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SARS-CoV-2 specific IgG antibodies at baseline (pre booster), and 6-months post booster vaccination
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Assessment method [1]
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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
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Timepoint [1]
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Baseline (pre booster), and 6-months post booster vaccination
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Secondary outcome [2]
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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)
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Assessment method [2]
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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.
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Timepoint [2]
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Baseline (pre booster), 28 days and 6 months post booster vaccination
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Secondary outcome [3]
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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
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Assessment method [3]
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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.
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Timepoint [3]
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Baseline (pre booster), 28 days-, and 6-months post booster vaccination
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Secondary outcome [4]
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Interferon gamma (IFN?) concentrations in International Units (IU)/mL
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Assessment method [4]
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Interferon gamma (IFN?) concentrations as a measurement of cellular immunity will be assessed on a subset (40%) of the participants from each group. QuantiFERON Human IFN-? SARS-CoV-2 (Qiagen) will be used to stimulate IFN-? production in peripheral blood mononuclear cells (PBMCs) and then IFN-? production will be measured using ELISA. Data will be presented as geometric mean concentration (GMC) and 95% confidence intervals (CI).
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Timepoint [4]
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Baseline (pre booster), 28 days-, and 6-months post booster vaccination
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Secondary outcome [5]
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Number of IFN? producing cells/million PBMCs
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Assessment method [5]
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IFN? producing cells as a measurement of cellular immunity will be assessed on a subset (40%) of the participants from each group. IFN-? Enzyme-Linked ImmunoSpot (Elispot) assay will be performed on isolated peripheral blood mononuclear cells (PBMCs). Data will be reported as number of IFN? producing cells/million and presented using means and 95% confidence intervals.
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Timepoint [5]
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Baseline (pre booster), 28 days-, and 6-months post booster vaccination
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Secondary outcome [6]
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Frequency of cytokine-expressing T cells
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Assessment method [6]
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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.
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Timepoint [6]
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Baseline (pre booster), 28 days-, and 6-months post booster vaccination
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Secondary outcome [7]
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Cytokine concentrations following PBMCs stimulation
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Assessment method [7]
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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.
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Timepoint [7]
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Baseline (pre booster), 28 days and 6-months post booster vaccination
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Secondary outcome [8]
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Incidence of unsolicited adverse events (AE)
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Assessment method [8]
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All unsolicited AE will be collected for 28 days post booster vaccination. Data will be presented as proportion of participants who report unsolicited AE.
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Timepoint [8]
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28 days-post booster vaccination
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Secondary outcome [9]
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Incidence of medically attended adverse events (AE)
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Assessment method [9]
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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.
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Timepoint [9]
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3 months post booster vaccination
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Secondary outcome [10]
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Incidence of serious adverse events (SAE)
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Assessment method [10]
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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.
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Timepoint [10]
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6 months post booster vaccination
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Eligibility
Key inclusion criteria
1. 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.
2. No confirmed SARS-CoV-2 infection on PCR or RAT within the last 3 months.
3. Willing and able to give written informed consent.
4. Aged 18 years or above.
5. Willing to complete the follow-up requirements of the study.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
Yes
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Key exclusion criteria
1. Currently receiving immunosuppressive medication or anti-cancer chemotherapy.
2. Known HIV infection.
3. Congenital immune deficiency syndrome.
4. Received immunoglobulin or other blood products in the three months prior to potential
study booster vaccination.
5. Study staff and their relatives.
6. Have a history of a severe allergic reaction to any COVID-19 vaccines or have a
medical exemption to receiving further COVID-19 vaccines.
7. Cannot read or understand English.
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Study design
Purpose of the study
Prevention
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Withdrawn
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
2/05/2022
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
30/11/2022
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Sample size
Target
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Royal Children's Hospital, Murdoch Children's Research Institute - Melbourne
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Recruitment postcode(s) [1]
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3052 - Melbourne
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Funding & Sponsors
Primary sponsor type
Other
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Name
Murdoch Childrens Research Institute
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Address
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Country
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Other collaborator category [1]
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Other
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Name [1]
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Coalition for Epidemic Preparedness Innovations
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Address [1]
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Country [1]
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Other collaborator category [2]
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Other
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Name [2]
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The Peter Doherty Institute for Infection and Immunity
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Address [2]
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Country [2]
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Ethics approval
Ethics application status
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Summary
Brief 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. Stage 1 will commence at the time of study approval and
transition to stage 2 once bivalent vaccines are approved and available in Australia.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT05543356
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Kim Mulholland, MD/Prof
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Address
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Murdoch Childrens Research Institute
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT05543356
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