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| Name | Class |
|---|---|
| Coalition for Epidemic Preparedness Innovations | OTHER |
| The Peter Doherty Institute for Infection and Immunity | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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]). |
|
| 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). |
|
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 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 |
| Measure | Description | Time Frame |
|---|---|---|
| SARS-CoV-2 Infections | 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 | 24 months post booster vaccination |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kim Mulholland, MD/Prof | Murdoch Childrens Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Children's Hospital, Murdoch Children's Research Institute | Melbourne | Victoria | 3052 | Australia |
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| Label | URL |
|---|---|
| Coalition for Epidemic Preparedness Innovations (CEPI). Priority List of Adverse Events of Special Interest: COVID-19 2020 \[Available from: | View source |
| World Health Organization. Interim statement on the use of additional booster doses of Emergency Use Listed mRNA vaccines against COVID-19 2022 | View source |
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The investigators 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.
Individual participant data (IPD) sharing plans in development
In development
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| ID | Title | Description |
|---|---|---|
| FG000 | Bivalent Moderna (mRNA-1273.214) | 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]). Bivalent Moderna: 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. |
| FG001 | Novavax | 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). Novavax: 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. |
| FG002 | Control Group- no Vaccine | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline |
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| 28 Days |
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| 6 Months |
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| 12 Months |
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| 18 Months |
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| ID | Title | Description |
|---|---|---|
| BG000 | Bivalent Moderna (mRNA-1273.214) | 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]). Bivalent Moderna: 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age is recorded as a continuous variable in years at the time of booster vaccination. Values are derived from date of birth and visit date, and summarised using mean, standard deviation, median, and range to describe the baseline age distribution of participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Moderna group:By day 28 1 participant was lost to follow-up and 1 had withdrawn Novavax: 4 people missed their visit for the day 28 blood draw and 1 was a withdrawal. | Posted | Geometric Mean | 95% Confidence Interval | binding antibody units (BAU/mL) | 28-days post booster vaccination |
|
Incidence of Unsolicited Adverse Events (AE) were collected 28 days-post booster vaccination
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bivalent Moderna (mRNA-1273.214) | 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]). Bivalent Moderna: 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute pancreatitis | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abortion induced | Surgical and medical procedures | MedDRA 10.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kathryn Bright | Murdoch Childrens Research Institute | +61 3 99366656 | kathryn.bright@mcri.edu.au |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 9, 2025 | Jul 31, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 20, 2025 | Mar 20, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D000090983 | 2019-nCoV Vaccine mRNA-1273 |
| C000722752 | mRNA-1273.214 COVID-19 vaccine |
| C000711928 | NVX-CoV2373 adjuvated lipid nanoparticle |
| ID | Term |
|---|---|
| D000087503 | mRNA Vaccines |
| D000087504 | Nucleic Acid-Based Vaccines |
| D014614 | Vaccines, Synthetic |
| D011994 | Recombinant Proteins |
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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.
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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.
|
|
| 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. |
|
| 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) | 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. | 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 | 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. | Baseline (pre booster), 6,12 and 18-months post booster vaccination |
| 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 (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). | Baseline (pre booster), Day 28, 6-months and 12-months post booster vaccination |
| Number of IFNγ Producing Cells/Million PBMCs | 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. | Baseline (pre booster), 6, 12 and 18-months post booster vaccination |
| Frequency of Cytokine-expressing T Cells | 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. | Baseline (pre booster), 6, 12 and 18 -months post booster vaccination |
| Cytokine Concentrations Following PBMCs Stimulation | 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. | Baseline (pre booster), 6, 12 and 18-months post booster vaccination |
| Incidence of Unsolicited Adverse Events (AE) | 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. | 28 days-post booster vaccination |
| 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 number of medically attended adverse events. Serious adverse events (SAEs) are reported separately. | 3 months post booster vaccination |
| Incidence of Serious Adverse Events (SAE) | 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. | 24 months post booster vaccination |
| US Food and Drug Administration (FDA). Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials 2007 | View source |
| 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 | View source |
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| NOT COMPLETED |
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| BG001 | Novavax | 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). Novavax: 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. |
| BG002 | Control Group- no Vaccine | 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. |
| BG003 | Total | Total of all reporting groups |
| Median |
| Inter-Quartile Range |
| years |
|
| Age, Customized | Age is summarised in two strata (≥18 to <50 and ≥50 years) because randomisation was stratified by these groups. Age in completed years was derived from date of birth and visit date. | Count of Participants | Participants |
|
| Sex: Female, Male | Sex was recorded as male or female based on participant self-report at enrolment. | Count of Participants | Participants |
|
| Region of Enrollment | Region of enrolment reflects the geographic location where participants entered the study. All participants were enrolled in Melbourne, Victoria, Australia. | Count of Participants | Participants |
|
| BMI | Body mass index (BMI) was calculated as weight in kilograms divided by height in metres squared (kg/m^2). BMI is presented as a continuous variable and summarised using the median and interquartile range | One participant is missing a weight measurement, as they declined the assessment. | Median | Inter-Quartile Range | kg/m^2 |
|
| Number of times tested positive for SARS-CoV-2 | Participants were asked whether they had ever tested positive for SARS-CoV-2 before enrolment. If yes, they were then asked how many times they had tested positive in separate instances of infection. | Count of Participants | Participants |
|
| Comorbidities | One participant is missing a weight measurement, as they declined the assessment. One participant is missing an observation for history of anaphylaxis. Therefore, there is an observation missing for the comorbidity of obesity (BMI ≥30 kg/m^2) and for history of anaphylaxis | Count of Participants | Participants |
|
| Race (NIH/OMB) | Race was self-reported and categorised according to U.S. OMB standards required by ClinicalTrials.gov. Participants identifying as Indigenous Australian were classified under 'American Indian or Alaska Native,' following ClinicalTrials.gov guidance for Indigenous populations. | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Ethnicity was self-reported and categorised using the two U.S. OMB classifications required by ClinicalTrials.gov: 'Hispanic or Latino' and 'Not Hispanic or Latino.' Participants who selected 'Prefer not to say' were classified as 'Unknown/Not Reported.' | Count of Participants | Participants |
|
| OG001 | Novavax | 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). Novavax: 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 | 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. | Solicited local and systemic reactions were collected for 7 days post-vaccination using a study-specific questionnaire. Outcomes are reported as both the number of participants in each arm and the percentage of participants in that arm experiencing reactions by severity grade. Reactions were graded on a 0-4 scale: Grade 0 = no symptom; Grade 1 = mild (does not interfere with activity); Grade 2 = moderate (may require non-narcotic analgesia); Grade 3 = severe (limits or prevents daily activity); | Posted | Count of Participants | Participants | Total incidence of solicited reactions will be measured for 7 days post booster vaccination |
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|
|
| Secondary | SARS-CoV-2 Specific IgG Antibodies at Baseline (Pre Booster), and 6,12 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 | One person in the Moderna group didn't have a blood taken at baseline | Posted | Geometric Mean | 95% Confidence Interval | binding antibody units (BAU/mL) | Baseline (pre booster), 6-months,12-months and 18-months post booster vaccination |
|
|
|
| Secondary | SARS-CoV-2 Specific Neutralising Antibodies Measured by Surrogate Virus Neutralization Test (sVNT) | 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. | No Day 28 samples collected from control group as they did not receive any vaccine. | Posted | Geometric Mean | 95% Confidence Interval | U/mL | Baseline (pre booster), 28 days, 6,12, 18, 24, and 30 months post booster vaccination |
|
|
|
| Secondary | 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 | 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. | Not Posted | Baseline (pre booster), 6,12 and 18-months post booster vaccination | Participants |
| Secondary | 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 (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). | No Day 28 samples collected for Control group as no vaccine were given. | Posted | Geometric Mean | 95% Confidence Interval | IU/mL | Baseline (pre booster), Day 28, 6-months and 12-months post booster vaccination |
|
|
|
| Secondary | Number of IFNγ Producing Cells/Million PBMCs | 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. | Not Posted | Baseline (pre booster), 6, 12 and 18-months post booster vaccination | Participants |
| Secondary | Frequency of Cytokine-expressing T Cells | 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. | Not Posted | Baseline (pre booster), 6, 12 and 18 -months post booster vaccination | Participants |
| Secondary | Cytokine Concentrations Following PBMCs Stimulation | 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. | Not Posted | Baseline (pre booster), 6, 12 and 18-months post booster vaccination | Participants |
| Secondary | Incidence of Unsolicited Adverse Events (AE) | 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. | Posted | Count of Participants | Participants | 28 days-post booster vaccination |
|
|
|
| Secondary | 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 number of medically attended adverse events. Serious adverse events (SAEs) are reported separately. | Posted | Number | Medically attended adverse events | 3 months post booster vaccination |
|
|
|
| Secondary | Incidence of Serious Adverse Events (SAE) | 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. | Posted | Number | Serious adverse events | 24 months post booster vaccination |
|
|
|
| Other Pre-specified | SARS-CoV-2 Infections | 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 | Posted | Number | Reported SARS-CoV-2 infections | 24 months post booster vaccination |
|
|
|
| 0 |
| 177 |
| 5 |
| 177 |
| 10 |
| 177 |
| EG001 | Novavax | 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). Novavax: 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. | 0 | 176 | 8 | 176 | 8 | 176 |
| EG002 | Controls | 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. | 0 | 143 | 8 | 143 | 1 | 143 |
| Appendicitis | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Bradyarrhythmia | Cardiac disorders | MedDRA 10.0 | Systematic Assessment |
|
| Diverticulitis | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 10.0 | Systematic Assessment |
|
| Hand tendon injury | Injury, poisoning and procedural complications | MedDRA 10.0 | Systematic Assessment |
|
| Infectious mononucleosis | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| Infective exacerbation of asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Injury | Injury, poisoning and procedural complications | MedDRA 10.0 | Systematic Assessment |
|
| Myocarditis | Cardiac disorders | MedDRA 10.0 | Systematic Assessment |
|
| Optic neuritis | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Ovarian cyst ruptured | Reproductive system and breast disorders | MedDRA 10.0 | Systematic Assessment |
|
| Ovarian haemorrhage | Reproductive system and breast disorders | MedDRA 10.0 | Systematic Assessment |
|
| Postpartum sepsis | Pregnancy, puerperium and perinatal conditions | MedDRA 10.0 | Systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 10.0 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA 10.0 | Systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | MedDRA 10.0 | Systematic Assessment |
|
| Urinary tract infection | Renal and urinary disorders | MedDRA 10.0 | Systematic Assessment |
|
| Uterine rupture | Pregnancy, puerperium and perinatal conditions | MedDRA 10.0 | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 10.0 | Systematic Assessment |
|
| Administration site pain | General disorders | MedDRA 10.0 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| Cervix carcinoma | Reproductive system and breast disorders | MedDRA 10.0 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 10.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 10.0 | Systematic Assessment |
|
| Heavy menstrual bleeding | Reproductive system and breast disorders | MedDRA 10.0 | Systematic Assessment |
|
| Laryngitis | Infections and infestations | MedDRA 10.0 | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 10.0 | Systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 10.0 | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA 10.0 | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D000086663 | COVID-19 Vaccines |
| D014765 | Viral Vaccines |
| D000941 | Antigens |
| D001685 | Biological Factors |
| Title | Measurements |
|---|---|
|
| Male |
|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
|
|
| Title | Measurements |
|---|---|
|
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Grade 2 Moderate |
|
| Grade 3 Severe |
|
| Grade 4 Potentially Life Threatening |
|
| Tenderness |
|
| Redness |
|
| Swelling |
|
| Hard |
|
| Axillary Lymphadenopathy |
|
| Warmth |
|
| Itch |
|
| Fever |
|
| Nausea |
|
| Vomiting |
|
| Diarrhoea |
|
| Headache |
|
| Fatigue/Malaise |
|
| Muscle pain |
|
| Joint pain |
|
| 28 day anti-spike IgG GMC (95% CI) (Note, controls did not have blood taken at 28 days) |
|
|
| 6 month anti-spike IgG GMC (95% CI) |
|
|
| 12 month anti-spike IgG GMC (95% CI) |
|
|
| 18 month anti-spike IgG GMC (95% CI) |
|
|
| 28 days Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI) |
|
|
| 6 months Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI) |
|
|
| 12 months Wuhan-Hu-1 SARS-CoV-2 sVNT U/mL GMC (95% CI) |
|
|
| Day 28 |
|
|
| Headache |
|
| Supraventricular tachycardia |
|
| Acne |
|
| Mouth ulceration |
|
| Heavy menstrual bleeding |
|
| Nasal congestion |
|
| Administration site pain |
|
| Road traffic accident |
|
| Tinnitus |
|
| No reported AE |
|