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Trial registered on ANZCTR


Registration number
ACTRN12622000411741
Ethics application status
Approved
Date submitted
21/02/2022
Date registered
10/03/2022
Date last updated
29/02/2024
Date data sharing statement initially provided
10/03/2022
Date results information initially provided
1/03/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
COVID-19 vaccine boost to enhance immunity (The Booster Study)
Scientific title
COVID-19 vaccine boost to enhance immunity in healthy adults aged 18-65 (The Booster Study)
Secondary ID [1] 306430 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 325264 0
Condition category
Condition code
Infection 322665 322665 0 0
Studies of infection and infectious agents
Respiratory 322666 322666 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A booster dose of the Moderna Bivalent Omicron vaccine delivered intramuscularly on enrolment
Intervention code [1] 322866 0
Prevention
Intervention code [2] 322928 0
Treatment: Drugs
Comparator / control treatment
A booster dose of the Moderna Bivalent Omicron vaccine (0.5 mL) delivered intramuscularly at 3 months post- enrolment..
Control group
Active

Outcomes
Primary outcome [1] 330519 0
The proportion of participants with a titre of blood neutralising antibodies to the SARS-CoV-2 Omicron variant of >1:100 in the immediate vaccination group.
Timepoint [1] 330519 0
Two weeks after the booster dose of Moderna Bivalent Omicron vaccine
Secondary outcome [1] 406515 0
A composite outcome of the number of reported adverse events (AEs) and serious adverse events (SAEs) in the immediate arm and the deferred arms, as recorded in the electronic case report form (CRF). Data will be collected by study staff from participants at study visits.
Specific AEs to be collected (using a specified Grade 1 - Grade 4 scale)
1) systemic events : headache, fatigue, new or worsened muscle pain, new or worsened joint pain
2) local reactions: pain at injection site, redness, swelling
3) Fever scale
4) Clinical symptoms of myocarditis/pericarditis: chest pain, shortness of breath, feelings of a fast-beating/fluttering or pounding heart

Serious adverse events as defined by the TGA Note for Guidance on Clinical Safety Management: Definitions and Standards for Expedited Reporting (CPMP/ICH/377/95)
Timepoint [1] 406515 0
At days 3, 5 and 7 after the receipt of the third vaccine dose in the immediate arm; which corresponds to at days 87, 89 and 91 in the deferred arm
Secondary outcome [2] 406516 0
The difference in mean titre of blood neutralising antibodies to the SARS-CoV-2 Omicron variant in the immediate compared to that in the delayed vaccination arm.
Timepoint [2] 406516 0
At time points D0 (receipt of 3rd dose), D3, D5, D7, D28, D84 and D168 in the immediate arm, which corresponds to time points D84, 87, 89, 91, 112 and 168 in the deferred arm
Secondary outcome [3] 407269 0
durability of mean titre of saliva neutralising antibodies to SARS-CoV-2
Timepoint [3] 407269 0
day 14, day 28, day 84 and 168 in the immediate arm; which corresponds to day 98, day 112 and day 168 in the deferred arm

Eligibility
Key inclusion criteria
Aged 18-65 years
• Healthy with no significant immunosuppressive illnesses. These include but are not limited to:
- cancer or treatment of cancer or organ transplantation
- treatment of auto-immune or inflammatory conditions such as inflammatory arthritis or inflammatory bowel disease
- use of corticosteroid, TNF inhibitor, interleukins, interferons, cyclosporine or other immunosuppressive medications
- significant renal or liver disease

• Two or 3 prior doses of a COVID-19 vaccine, the last dose at least 4 months prior to recruitment
• No previous significant adverse events to 2-3 prior doses of COVID-19 vaccine, according to the criteria below. Severe grading indicates the event prevented daily activity, temperature >40.0°C or >10.0 cm in diameter for redness and swelling at the site of injection

- severe systemic events (fatigue, headache, fever, muscle or joint pain)
- severe local events (pain at injection site, redness and swelling
- any event requiring emergency department visit or hospitalisation
• No prior anaphylaxis to any cause, including to prior CIVID-19 vaccines
• No prior cardiac inflammatory condition (myocarditis, pericarditis), including to prior COVID-19 vaccines
• Willing and available to have regular blood and saliva samples taken per the schedule of events
• Willing to be randomly assigned to receive a booster dose of Moderna Bivalent Omicron vaccine either upon enrolment or 3 months later
• Willing to provide a signed and dated informed consent form.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Prior COVID-19 infection
• Pregnant or breastfeeding women and women planning to become pregnant
• Unwilling to use reliable contraception around the timing of the vaccine (one month before and one month after)
• Receiving medication that might reduce immune responses. These include but are not limited to:
- systemic corticosteroids
- interleukins
- interferons
- cyclosporine
- systemic chemotherapy

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/03/2022
Actual
4/11/2022
Date of last participant enrolment
Anticipated
30/09/2022
Actual
30/01/2023
Date of last data collection
Anticipated
31/10/2023
Actual
2/12/2023
Sample size
Target
64
Accrual to date
Final
52
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 310777 0
Government body
Name [1] 310777 0
National Health and Medical Research Council
Country [1] 310777 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
Grattan St
Parkville, Vic 3010
Country
Australia
Secondary sponsor category [1] 312016 0
None
Name [1] 312016 0
Address [1] 312016 0
Country [1] 312016 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310352 0
Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 310352 0
Level 2
South West
300 Grattan Street
Parkville Victoria 3050
Ethics committee country [1] 310352 0
Australia
Date submitted for ethics approval [1] 310352 0
Approval date [1] 310352 0
06/10/2021
Ethics approval number [1] 310352 0
HREC/78656/MH-2021

Summary
Brief summary
This study is a randomised open-label trial of the Moderna Omicron-containing bivalent booster candidate mRNA-1273.214 (mRNA-1273.214) vaccine. Participants who have received 2-3 prior doses of the any COVID-19 vaccine will be randomised into two arms: to receive a 3rd dose of the Moderna Bivalent Omicron vaccine on enrolment or 3 months later. Both groups will be followed-up for six months after enrolment.. We hypothesise that there will be a difference in measurable SARS-CoV-2 antibody responses in people who receive a Moderna Bivalent Omicron COVID vaccine booster immediately on enrolment in the study compared to those who wait an additional three months before receiving a booster dose.

A booster dose of the Moderna Bivalent Omicron r vaccine will be administered intramuscularly. One dose (0.5 mL) contains 50 micrograms of mRNA-1273.214 (25-µg each ancestral Wuhan-Hu-1 and omicron B.1.1.529 spike SARS-CoV-2 mRNAs) (embedded in lipid nanoparticles).
This is a single-site study with interested potential participants attending the Royal Melbourne Hospital for recruitment, the consenting process and study visits. A total of 64 participants will be recruited (32 per arm).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 117346 0
Prof Stephen Kent
Address 117346 0
The Peter Doherty Institute for Infection and Immunity
792 Elizabeth Street
Melbourne, VIC 3000
Country 117346 0
Australia
Phone 117346 0
+61 03 8344 9939
Fax 117346 0
Email 117346 0
skent@unimelb.edu.au
Contact person for public queries
Name 117347 0
Dr Jennifer Audsley
Address 117347 0
The Peter Doherty Institute for Infection and Immunity
792 Elizabeth Street
Melbourne, VIC 3000
Country 117347 0
Australia
Phone 117347 0
+61 03 8344 3266
Fax 117347 0
Email 117347 0
jennifer.audsley@unimelb.edu.au
Contact person for scientific queries
Name 117348 0
Prof Stephen Kent
Address 117348 0
The Peter Doherty Institute for Infection and Immunity
792 Elizabeth Street
Melbourne, VIC 3000
Country 117348 0
Australia
Phone 117348 0
+61 03 8344 9939
Fax 117348 0
Email 117348 0
skent@unimelb.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
After de-identification, individual participant data that underlie any published results
When will data be available (start and end dates)?
Commencing 3 months after and ending 5 years following article publication
Available to whom?
Investigators whose proposed use of the data has been approved by the Booster Study Protocol Steering Committee
Available for what types of analyses?
For individual participant meta-analysis
How or where can data be obtained?
Proposals may be submitted up to 5 years following article publication. Proposals should be directed to skent@unimelb.edu.au

To gain access data requestors will need to sign a data access agreement. Data will be available for 5 years at The University of Melbourne Research Repository which is found at:
https://melbourne.figshare.com/


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
15162Study protocol  skent@unimelb.edu.au
15165Ethical approval  skent@unimelb.edu.au



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseInterim results from a phase I randomized, placebo-controlled trial of novel SARS-CoV-2 beta variant receptor-binding domain recombinant protein and mRNA vaccines as a 4th dose booster.2023https://dx.doi.org/10.1016/j.ebiom.2023.104878
N.B. These documents automatically identified may not have been verified by the study sponsor.