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Trial registered on ANZCTR


Registration number
ACTRN12622000238774
Ethics application status
Approved
Date submitted
27/01/2022
Date registered
10/02/2022
Date last updated
15/04/2024
Date data sharing statement initially provided
10/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised trial to evaluate the immune response of COVID-19 vaccines in adults and adolescents
Scientific title
Platform Trial In COVID-19 Vaccine BOOsting (PICOBOO) - A single blinded, phase IV, adaptive randomised trial to evaluate the immunogenicity of COVID-19 booster vaccines in adults and adolescents
Secondary ID [1] 306205 0
None
Universal Trial Number (UTN)
Trial acronym
PICOBOO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 324914 0
Condition category
Condition code
Infection 322348 322348 0 0
Other infectious diseases
Respiratory 322386 322386 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will receive a single intramuscular dose of vaccine administered by a study nurse:
Arm 1: COMIRNATY Omicron XBB.1.5 (raxtozinameran), 30 µg contained in 0.3ml of the diluted vaccine

Arm 2: SPIKEVAX XBB.1.5 (andusomeran), 50µg contained in 0.5ml of the diluted vaccine

Arm 3: NUVAXOVID XBB.1.5, 5µg of SARS-CoV spike protein adjuvanted with Matrix-M in 0.5ml of the diluted vaccine
Intervention code [1] 322608 0
Treatment: Drugs
Comparator / control treatment
Participants will receive a single intramuscular dose of vaccine administered by a study nurse:

Arm 1: COMIRNATY Omicron XBB.1.5 (raxtozinameran), 30 µg contained in 0.3ml of the diluted vaccine
Control group
Dose comparison

Outcomes
Primary outcome [1] 330152 0
Serum concentrations of SARS-CoV-2 anti-spike Immunoglobulin (IgG)
Timepoint [1] 330152 0
Day 28 after randomisation
Secondary outcome [1] 405065 0
Serum concentrations of SARS-CoV-2 anti-spike Immunoglobulin (IgG)
Timepoint [1] 405065 0
Day 7, 84, 365 after randomisation for adult participants and Day 7 and 180 for adolescent participants
Secondary outcome [2] 405066 0
Serum concentrations of neutralising SARS-CoV-2 antibodies
Timepoint [2] 405066 0
Day 28, 84, 365 after randomisation for adult participants and Day 28 and 180 for adolescent participants
Secondary outcome [3] 405067 0
Cellular immune responses to SARS-CoV-2 assessed from peripheral blood mononuclear cells (PBMCs). This is an exploratory outcome.
Timepoint [3] 405067 0
Day 7, 28, 84, 365 after randomisation for adult participants and Day 28 and 180 for adolescent participants
Secondary outcome [4] 405068 0
Concentrations of mucosal salivary anti-RBD IgA and IgG to SARS-CoV2
Timepoint [4] 405068 0
Day 28, 84 and 365 after randomisation for adult participants and Day 28 and 180 for adolescent participants
Secondary outcome [5] 405069 0
Local and systemic reactions assessed daily via text message surveys (designed specifically for this study) up to Day 7 after randomisation graded as no reaction, mild, moderate, severe, or life-threatening.
Timepoint [5] 405069 0
Up to Day 7 after randomisation
Secondary outcome [6] 405071 0
Hospitalisation resulting from adverse events following immunisation (AEFI) ascertained by blinded study nurse during day 28 visit (or follow-up telephone call)
Timepoint [6] 405071 0
up to Day 28 after randomisation
Secondary outcome [7] 405072 0
Any PCR-confirmed SARS-CoV-2 OR rapid antigen test (RAT) positive result for SARS-CoV-2
Timepoint [7] 405072 0
up to Day 720 after randomisation
Secondary outcome [8] 405073 0
Any PCR-confirmed SARS-CoV-2 infection
Timepoint [8] 405073 0
up to Day 720 after randomisation
Secondary outcome [9] 405074 0
Any PCR-confirmed ancestral or variant-type SARS-CoV-2 infection
Timepoint [9] 405074 0
up to Day 720 after randomisation
Secondary outcome [10] 405075 0
Medically attended, PCR-confirmed or RAT-positive SARS-CoV-2 infection
Timepoint [10] 405075 0
up to Day 720 after randomisation
Secondary outcome [11] 405076 0
Hospitalisation for management of PCR-confirmed or RAT-positive SARS-CoV-2 infection ascertained by blinded study nurse during study visit, direct communication with the study team by the participant or text message survey.
Timepoint [11] 405076 0
up to Day 720 after randomisation
Secondary outcome [12] 405077 0
Participant-reported time off work, study or usual activities due to PCR-confirmed or RAT-positive SARS-CoV-2 infection via text message survey (designed specifically for this study)
Timepoint [12] 405077 0
up to Day 720 after randomisation
Secondary outcome [13] 420736 0
Time off work, study or usual activities for the legal guardian of a participant under the age of 18 due to PCR-confirmed or RAT-positive SARS-CoV-2 infection for the child under their care. Via text message survey (designed specifically for this study)
Timepoint [13] 420736 0
up to Day 720 after randomisation
Secondary outcome [14] 420737 0
% inhibition of (wild-type or variant(s) of concern) SARS-CoV-2. These will be obtained from Viral Surrogate Neutralisation tests from blood serum samples.
Timepoint [14] 420737 0
Day 28, 84, 365 after randomisation for adult participants and Day 28 and 180 for adolescent participants
Secondary outcome [15] 420738 0
Number of IFN-gamma spot forming cells per 10^6 peripheral blood mononuclear cells following in vitro stimulation with SARS-CoV-2 wild-type or variant(s) of concern spike peptide pools for CD4 T cell or independently CD8 T cell epitopes
Timepoint [15] 420738 0
Days 7, 28, 84, 365 after randomisation for adult participants and Day 28 and 180 for adolescent participants

Eligibility
Key inclusion criteria
To be eligible a person must:
1. Be equal to or over 12 years of age.
2 .Have received:
-two doses of BNT162b2 and be less than 70 years old OR
-two doses of ChAdOx1-S and be equal to or over 50 years old OR
-two doses of mRNA1273 and be between 12 and 18 years old.
3. Be willing to receive a COVID-19 vaccine authorised for use (including emergency use authorisation) by the TGA or equivalent regulatory authority.
4. Be registered on the Australian Immunisation Register (AIR), or otherwise possess evidence of primary vaccination.
5. Be willing to comply with trial requirements, including the provision of blood and saliva samples at the indicated time intervals.
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
A person is not eligible if they:
1. Have received a COVID-19 booster vaccine in the preceding 3 months
2. Individuals who are contraindicated to receive any of the COVID-19 study vaccines. E.g. have a history of anaphylaxis to a vaccine component or myocarditis attributed to previous receipt of a messenger ribonucleic acid (mRNA) vaccine.
3. Are severely immunocompromised or have a known immunodeficiency.

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)
A computer generated randomisation list, generated by the study statistician will be uploaded to the study database by the study data manager, randomisation will then occur within the study database upon enrolment of the participant and completion of the information required for stratification. The randomisation list will be concealed and password protected. Study nurses performing the randomisation will not have access to the randomisation list nor will any other personel except the unblinded statistician and data manager.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A sequence of intervention assignments will be generated by an un-blinded trial statistician using random permuted blocks for each stratum:
Adolescents aged 12 - 17 who have received two doses of BNT162b2,
Adolescents aged 12 - 17 who have received two doses of mRNA1273,
Adults aged 18 - 49 who have received two doses of BNT162b2,
Adults aged 50 - 69 who have received two doses of BNT162b2,
Adults aged 50 - 69 who have received two doses of ChAdOx1-S,
Adults aged 70 or above who have received two doses of ChAdOx1-S,
using computer software with a validated random number generator and equal allocation for all booster interventions.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
At vaccination, an un-blinded member of the research team will dispense and administer the study vaccine to a blinded participant. Pre-filled syringes containing one of the COVID-19 booster vaccines approved for use will be covered with opaque tape and concealed in an opaque box until ready for administration. Prior to opening the box, the participant will be asked to look away. The member of the research team will administer the study vaccine per the Australian guidelines.
Research staff involved in the follow-up of adverse reactions will be blinded to the group assignment of the participants.
Laboratory staff processing or analysing trial specimens will be blinded to the group assignment of participants.
Trial analysts preparing interim reports will be un-blinded and unmasked.
Researchers involved with the trial design adaptations will be blinded to trial results unless pre-specified criteria are met for public disclosure of results.
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Design: PICOBOO is a three-arm parallel group adaptive trial for SARS-CoV-2 booster vaccine doses, with strata based on vaccine history (ChAdOx1-S/ChAdOx1-S, BNT162b2/BNT162b2 or mRNA1273/mRNA1273 vaccine priming) and age group (12 to <18y, 18 to <50y, 50 to <70y, >=70y), but has the capacity to accommodate additional vaccine brands, doses or schedules, as both novel vaccines and policy evolves over time. Immune responses and reactogenicity to COVID-19 vaccines will be assessed on an intent-to-treat and a modified intent-to-treat population after the removal of participants who have a laboratory confirmed SARS-CoV-2 infection after randomisation and prior to providing blood samples for the primary outcome, between Day 21-31 after randomisation.

Baseline characteristics will be summarised on the ITT populations by strata and intervention arm using mean and standard deviation or median and interquartile range for continuous variables, as appropriate, and frequency and percentage for categorical variables.

Efficacy analyses: A Bayesian three-level hierarchical linear model will be used for the primary analysis as it is anticipated that there may be similarities in immune responses across COVID-19 booster dose, age groups and potentially across mRNA vaccine interventions (BNT162b2 and mRNA1273). The model estimates the posterior distribution of the mean log10 anti-spike SARS-CoV-2 lgG antibody against SARS-CoV-2 measured ~28 days after receipt of the assigned booster COVID-19 vaccine for each intervention and booster dose in each stratum and is adjusted for the time epoch relative to randomisation, log10 anti-spike SARS-CoV-2 lgG antibody immediately prior to booster vaccine administration, site and sex. The priors for the hierarchical parameters are weakly informative to allow for the information borrowing across booster dose numbers, age groups or mRNA vaccine interventions to be data driven. A similar model will be used to model all continuous immune response endpoints.

Interims, Decision Criteria & Adaptations: Up to seven scheduled analyses will be performed; the first analysis will be performed after eligible participants have completed 300 vaccine booster occasions and have completed 21-31 days of follow-up post randomisation. Thereafter, analyses will be performed after every 150 additional vaccine booster occasions, until the maximum recruitment of 1,000 participants, contributing approximately 1,200 vaccine booster occasions is reached. Recruitment to a stratum will be ceased if the width of the respective 95% highest density posterior credible interval for the mean log10 anti-spike SARS-CoV-2 lgG antibody meets the precision criteria. The precision threshold, or maximum interval width, is 0.2 on the log10, scale; assuming an approximately symmetric posterior distribution, this equates to a multiplicative reduction of 0.7943 and increase of 1.2589 on the untransformed scale.

Safety analysis: All binary safety endpoints will be modelled with a Bayesian logistic model. This model estimates the posterior probability of the log odds of an adverse outcome in each intervention for each COVID-19 booster dose within each stratum.

Sample size and power: Trial operating characteristics were computed using 5,000 simulations and a range of plausible values for the means and standard deviations in each stratum, assuming a maximum sample size of 1,000 participants providing approximately 1,200 vaccine booster occasions, 5% loss to follow up between 21-31 days after randomisation and uniformly distributed accrual within 12 months. Parameter values for the means and standard deviations of the geometric mean log10 anti-spike SARS-CoV-2 lgG antibody against SARS-CoV-2 concentrations (GMC) were estimated from the COV-BOOST (Phase 2) trial publication. Across all simulated scenarios, the precision threshold was exceeded, and recruitment was ceased in at least five booster dose numbers within strata in over 76% of simulations. These trial operating characteristics are robust to the plausible range of geometric mean concentrations.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
21/02/2022
Actual
29/03/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
1000
Accrual to date
885
Final
Recruitment in Australia
Recruitment state(s)
SA,TAS,WA
Recruitment hospital [1] 21469 0
Perth Children's Hospital - Nedlands
Recruitment hospital [2] 21470 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [3] 21471 0
Launceston General Hospital - Launceston
Recruitment postcode(s) [1] 36373 0
6009 - Nedlands
Recruitment postcode(s) [2] 36374 0
5006 - North Adelaide
Recruitment postcode(s) [3] 36375 0
7250 - Launceston

Funding & Sponsors
Funding source category [1] 310553 0
Government body
Name [1] 310553 0
National Health and Medical Research Council (NHMRC)
Country [1] 310553 0
Australia
Funding source category [2] 310577 0
Charities/Societies/Foundations
Name [2] 310577 0
Snow Medical Research Foundation
Country [2] 310577 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Telethon Kids Institute
Address
Northern Entrance, Perth Children's Hospital, 15 Hospital Avenue, Nedlands, Western Australia, 6009
Country
Australia
Secondary sponsor category [1] 311761 0
None
Name [1] 311761 0
Address [1] 311761 0
Country [1] 311761 0
Other collaborator category [1] 282128 0
University
Name [1] 282128 0
University of Adelaide
Address [1] 282128 0
Adelaide SA 5005
Country [1] 282128 0
Australia
Other collaborator category [2] 282129 0
University
Name [2] 282129 0
University of Tasmania
Address [2] 282129 0
Churchill Ave, Hobart TAS 7005
Country [2] 282129 0
Australia
Other collaborator category [3] 282130 0
University
Name [3] 282130 0
Royal Melbourne Institute of Technology
Address [3] 282130 0
La Trobe St, Melbourne VIC 3000
Country [3] 282130 0
Australia
Other collaborator category [4] 282131 0
University
Name [4] 282131 0
University of Western Australia
Address [4] 282131 0
Stirling Hwy, Crawley WA 6009
Country [4] 282131 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310163 0
Child and Adolescent Health Service Human Research Ethics Committee (EC00268)
Ethics committee address [1] 310163 0
Perth Children's Hospital, 15 Hospital Avenue, Nedlands, Western Australia, 6009
Ethics committee country [1] 310163 0
Australia
Date submitted for ethics approval [1] 310163 0
22/12/2021
Approval date [1] 310163 0
18/01/2022
Ethics approval number [1] 310163 0
RGS5222

Summary
Brief summary
The PICOBOO study platform is designed to be an adaptive randomised trial to evaluate the safety and effectiveness of COVID-19 booster vaccine strategies in the Australian context. This will enable regulators, researchers and policymakers to flexibly respond to new policy questions as they arise, for example as new vaccine formulations become available and new variants arise in Australia necessitating changes in strategy. This study aims to evaluate, pragmatically and efficiently, the immunogenicity and reactogenicity offered by alternative booster vaccination strategies against SARS-CoV-2. This adaptive trial is designed to allow for perpetual enrolment for as long as is needed to generate high-quality data to inform Australia's national COVID-19 booster vaccination practice and policy.
Trial website
Trial related presentations / publications
Public notes
Protocol and Statistical Analysis Plan will be published after ethics approval has been obtained.

Contacts
Principal investigator
Name 116710 0
Prof Peter Richmond
Address 116710 0
Perth Children's Hospital, 15 Hospital Avenue, Nedlands, Western Australia, 6009

Country 116710 0
Australia
Phone 116710 0
+61 08 6456 5604
Fax 116710 0
Email 116710 0
[email protected]
Contact person for public queries
Name 116711 0
Prof Peter Richmond
Address 116711 0
Perth Children's Hospital, 15 Hospital Avenue, Nedlands, Western Australia, 6009
Country 116711 0
Australia
Phone 116711 0
+61 08 6456 5604
Fax 116711 0
Email 116711 0
[email protected]
Contact person for scientific queries
Name 116712 0
Dr Charlie McLeod
Address 116712 0
Perth Children's Hospital, 15 Hospital Avenue, Nedlands, Western Australia, 6009
Country 116712 0
Australia
Phone 116712 0
+61 08 6319 1197
Fax 116712 0
Email 116712 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All non-identifiable individual patient data will be made available subject to approval by the Coordinating Principal Investigator.
When will data be available (start and end dates)?
From 1 months after publication of clinical trial results. No end date determined.
Available to whom?
On a case-by-case basis at the discretion of the Coordinating Principle Investigator to researchers who provide a methodologically sound proposal.
Available for what types of analyses?
Analyses to achieve the aims in the approved proposal only.
How or where can data be obtained?
Access via secure file transfer subject to approvals by Coordinating Principal Investigator (Professor Peter Richmond, [email protected])


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseCore protocol for the adaptive Platform Trial In COVID-19 Vaccine priming and BOOsting (PICOBOO).2023https://dx.doi.org/10.1186/s13063-023-07225-z
N.B. These documents automatically identified may not have been verified by the study sponsor.