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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/NCT05168709




Registration number
NCT05168709
Ethics application status
Date submitted
22/12/2021
Date registered
23/12/2021
Date last updated
9/02/2023

Titles & IDs
Public title
Investigating COVID-19 Vaccine Immunity in Children in the Melbourne Infant Study of BCG for Allergy and Infection Reduction
Scientific title
A Single-arm Clinical Trial to Investigate COVID-19 Specific Vaccine and Heterologous Immunity in the Melbourne Infant Study of BCG for Allergy and Infection Reduction (COSI BAIR)
Secondary ID [1] 0 0
81771
Universal Trial Number (UTN)
Trial acronym
COSI BAIR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 0 0
Vaccine Reaction 0 0
Immunization; Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Tozinameran

Experimental: Approved COVID-19 vaccination - The approved COVID-19 vaccination arm will receive the COMIRNATY™ (tozinameran - BNT162b2 [mRNA]) COVID-19 VACCINE. The dose, strength of the dose unit, dosing interval and dosing period of tozinameran used in this trial will be as approved by the Therapeutic Goods Administration (TGA) and recommended by the Australian Technical Advisory Group on Immunisation (ATAGI) for children aged 5 to <12 years of age. The recommended dose of tozinameran for this age group is 10 µg (0.2 mL) and the recommended schedule is 2 doses, 8 weeks apart. Therefore two tozinameran doses of 10µg (0.2 mL) will be administered intramuscularly 8-weeks apart as part of this arm of the trial.


Other interventions: Tozinameran
Tozinameran 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)
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean change from baseline of in vitro whole blood stimulation cytokine responses to COVID-19 specific and heterologous stimulants
Timepoint [1] 0 0
Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)
Secondary outcome [1] 0 0
Mean change from baseline of anti-SARS-CoV-2 antibody titres
Timepoint [1] 0 0
Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)
Secondary outcome [2] 0 0
Mean change from baseline of SARS-CoV-2-reactive T cell responses
Timepoint [2] 0 0
Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)
Secondary outcome [3] 0 0
Correlation of serological profiling of previous viral infections and antiviral responses, and post-vaccination anti-SARS-CoV-2 antibody titres
Timepoint [3] 0 0
Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)
Secondary outcome [4] 0 0
Correlation of serological profiling of vaccine-preventable disease antibody responses and post-vaccination anti-SARS-CoV-2 antibody titres
Timepoint [4] 0 0
Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)
Secondary outcome [5] 0 0
Correlation of whole blood cytokine responses to vaccine-preventable disease antigens and post-vaccination anti-SARS-CoV-2 antibody titres
Timepoint [5] 0 0
Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)
Secondary outcome [6] 0 0
Mean change from baseline of vaccine-preventable disease antibody titres
Timepoint [6] 0 0
Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)

Eligibility
Key inclusion criteria
- Age between five and eleven years (i.e. prior to the twelfth birthday) at the time of
enrolment,

- Participant who was randomised in the MIS BAIR trial, and

- Was randomly allocated to receive and received BCG as part of the MIS BAIR trial,
OR,

- Was randomly allocated to not receive and did not receive BCG;

- Is an individual whose parent/legally acceptable representative (LAR) consented to be
contacted about future ethically approved research, during the MIS BAIR trial consent
process, AND

- Has a parent/LAR capable of understanding the parent/LAR information statement and
consent form (PICF) document and providing consent on the participant's behalf.
Minimum age
5 Years
Maximum age
11 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Has a known hypersensitivity to the active ingredient or any of the excipients in
tozinameran,

- Has a prior polymerase chain reaction (PCR)-confirmed diagnosis of COVID-19 whether
symptomatic or not,

- Has received a COVID-19 vaccine (approved by the TGA or otherwise) prior to trial
enrolment,

- An individual and/or parent/legally acceptable representative who is unwilling or
unable to give written informed consent,

- An individual and/or parent/legally acceptable representative who is unwilling or
unable to consent to attend all scheduled study visits,

- An individual and/or parent/LAR who is unwilling or unable to give consent for blood
samples to be taken from the trial participant at each study visit, and

- Has or has had a clinically significant medical morbidity (e.g. immunocompromised
because of congenital or acquired disorders or immunosuppressive medical treatment; a
bleeding disorder; a recent history of inflammatory cardiac illness within the past 6
months, e.g., myocarditis, pericarditis, endocarditis, acute rheumatic fever (with
active myocardial inflammation) or acute rheumatic heart disease, or acute
decompensated heart failure), and

- Has received BCG at any other time than as part of the MIS BAIR trial.

Study design
Purpose of the study
Basic Science
Allocation to intervention
N/A
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
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/01/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
29/09/2022
Sample size
Target
Accrual to date
Final
51
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Melbourne Children's campus - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The COSI BAIR trial will involve approximately 60 children, aged 5 to 8 years old, comprising
a subset of participants from the Melbourne Infant Study BCG for Allergy and Infection
Reduction (MIS BAIR) randomised controlled trial. The overall aim of this trial is to
investigate the specific and heterologous effects of COVID-19 vaccination on immunity in
children. COSI BAIR will aim to recruit its participants from the MIS BAIR Bacillus
Calmette-Guérin (BCG)-naïve group. These children will be followed up until 28 days after
their final Coronavirus Disease 2019 (COVID-19) vaccination.

Venous blood samples will be collected at two study visits, at Murdoch Children's Research
Institute (MCRI):

1. Day 0 - baseline (day of COVID-19 vaccination #1), and

2. Day 84 (28 days after COVID-19 vaccination #2).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05168709
Trial related presentations / publications
Freyne B, Messina NL, Donath S, Germano S, Bonnici R, Gardiner K, Casalaz D, Robins-Browne RM, Netea MG, Flanagan KL, Kollmann T, Curtis N; Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR) Group. Neonatal BCG Vaccination Reduces Interferon-gamma Responsiveness to Heterologous Pathogens in Infants From a Randomized Controlled Trial. J Infect Dis. 2020 Jun 11;221(12):1999-2009. doi: 10.1093/infdis/jiaa030.
Freyne B, Donath S, Germano S, Gardiner K, Casalaz D, Robins-Browne RM, Amenyogbe N, Messina NL, Netea MG, Flanagan KL, Kollmann T, Curtis N. Neonatal BCG Vaccination Influences Cytokine Responses to Toll-like Receptor Ligands and Heterologous Antigens. J Infect Dis. 2018 May 5;217(11):1798-1808. doi: 10.1093/infdis/jiy069.
Messina NL, Pittet LF, Gardiner K, Freyne B, Francis KL, Zufferey C, Abruzzo V, Morrison C, Allen KJ, Flanagan KL, Ponsonby AL, Robins-Browne R, Shann F, South M, Vuillermin P, Donath S, Casalaz D, Curtis N. Neonatal Bacille Calmette-Guerin Vaccination and Infections in the First Year of Life: The MIS BAIR Randomized Controlled Trial. J Infect Dis. 2021 Oct 13;224(7):1115-1127. doi: 10.1093/infdis/jiab306.
Messina NL, Gardiner K, Donath S, Flanagan K, Ponsonby AL, Shann F, Robins-Browne R, Freyne B, Abruzzo V, Morison C, Cox L, Germano S, Zufferey C, Zimmermann P, Allen KJ, Vuillermin P, South M, Casalaz D, Curtis N. Study protocol for the Melbourne Infant Study: BCG for Allergy and Infection Reduction (MIS BAIR), a randomised controlled trial to determine the non-specific effects of neonatal BCG vaccination in a low-mortality setting. BMJ Open. 2019 Dec 15;9(12):e032844. doi: 10.1136/bmjopen-2019-032844.
Zimmermann P, Donath S, Perrett KP, Messina NL, Ritz N, Netea MG, Flanagan KL, van der Klis FRM, Curtis N; MIS BAIR group. The influence of neonatal Bacille Calmette-Guerin (BCG) immunisation on heterologous vaccine responses in infants. Vaccine. 2019 Jun 19;37(28):3735-3744. doi: 10.1016/j.vaccine.2019.03.016. Epub 2019 May 29.
Pittet LF, Messina NL, Gardiner K, Freyne B, Abruzzo V, Francis KL, Morrison C, Zufferey C, Vuillermin P, Allen KJ, Ponsonby AL, Robins-Browne R, Shann F, Flanagan KL, Phillips R, Donath S, Casalaz D, Curtis N. Prevention of infant eczema by neonatal Bacillus Calmette-Guerin vaccination: The MIS BAIR randomized controlled trial. Allergy. 2022 Mar;77(3):956-965. doi: 10.1111/all.15022. Epub 2021 Aug 9.
Public notes

Contacts
Principal investigator
Name 0 0
Nigel Curtis
Address 0 0
Murdoch Children's Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05168709