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COVID-19Phase 4COSI BAIRNCT05168709

Investigating COVID-19 Vaccine Immunity in Children in the Melbourne Infant Study of BCG for Allergy and Infection Reduction

A Phase 4 study testing Tozinameran in people with COVID-19 and Vaccine Reaction, run by Murdoch Childrens Research Institute at 1 site in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 5 to 11 yearsHealthy volunteers can take part
What is being tested?
Tozinameran
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
1 siteAustralia
Study dates
20 Jan 2022to 29 Sep 2022
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 5 to 11 years
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Australia1 site
  • Melbourne Children's campus

    Parkville, Victoria, 3052

Other trials in Australia

About this study

Official 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)

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).
Being tested
Tozinameran
Keywords
Non-specific effects, COVID-19 vaccination, paediatric vaccination, heterologous immunity, mRNA vaccine
Medical subject headings
COVID-19, Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TozinameranBiological

    Also called COMIRNATY, BNT162b2 [mRNA], Pfizer COVID-19 Vaccine

    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)

Study groups in NCT05168709
Study groupRoleWhat they receive
Approved COVID-19 vaccinationExperimentalThe 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.
Receives: Biological: Tozinameran

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean change from baseline of in vitro whole blood stimulation cytokine responses to COVID-19 specific and heterologous stimulants

    The difference in cytokine concentrations between those measured on the day of first vaccination and 28 days after second vaccination is the primary outcome measure

    Measured: Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)

Secondary outcomes (6)
  1. Mean change from baseline of anti-SARS-CoV-2 antibody titres

    The difference in anti-SARS-CoV-2 antibody titres between those measured on the day of first vaccination and 28 days after second vaccination is outcome measure 2

    Measured: Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)

  2. Mean change from baseline of SARS-CoV-2-reactive T cell responses

    The difference in SARS-CoV-2-reactive T cell responses, as measured by interferon-gamma producing units, between those measured on the day of first vaccination and 28 days after second vaccination is outcome measure 3

    Measured: Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)

  3. Correlation of serological profiling of previous viral infections and antiviral responses, and post-vaccination anti-SARS-CoV-2 antibody titres

    Pearson product-moment correlation coefficient of all trial participants' serological profiling of previous viral infections and antiviral responses on the day of first COVID-19 vaccination and anti-SARS-CoV-2 antibody titres measured at 28 days after second vaccination is outcome measure 4. Previous viral infection organisms considered will include SARS-CoV-1, Middle East Respiratory Syndrome Coronavirus and circulating coronaviruses (eg. human coronavirus HKU1).

    Measured: Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)

  4. Correlation of serological profiling of vaccine-preventable disease antibody responses and post-vaccination anti-SARS-CoV-2 antibody titres

    Pearson product-moment correlation coefficient of all trial participants' vaccine-preventable disease antibody responses on the day of first COVID-19 vaccination and anti-SARS-CoV-2 antibody titres measured at 28 days after second vaccination is outcome measure 5. Vaccine-preventable disease organisms examined will include Haemophilus influenzae B, Streptococcus pneumoniae and measles.

    Measured: Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)

  5. Correlation of whole blood cytokine responses to vaccine-preventable disease antigens and post-vaccination anti-SARS-CoV-2 antibody titres

    Pearson product-moment correlation coefficient of all trial participants' whole blood cytokine responses to vaccine-preventable disease antigens on the day of first COVID-19 vaccination and anti-SARS-CoV-2 antibody titres measured at 28 days after second vaccination is outcome measure 6. Vaccine-preventable disease organisms examined will include Haemophilus influenzae B, Streptococcus pneumoniae and measles.

    Measured: Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)

  6. Mean change from baseline of vaccine-preventable disease antibody titres

    The difference in vaccine-preventable disease antibody titres between those measured on the day of first vaccination and 28 days after second vaccination is outcome measure 7. Vaccine-preventable disease organisms examined will include Haemophilus influenzae B, Streptococcus pneumoniae and measles.

    Measured: Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Dec 2021
  2. Study start20 Jan 2022
  3. Primary completion29 Sep 2022
  4. Study completion29 Sep 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Model description
This trial is a non-controlled single-arm post-marketing exploratory trial where the approved COVID-19 vaccine will be used to determine whether COVID-19 vaccination alters heterologous (non-COVID-19-specific) immunity in children.
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05168709
Sponsor's protocol ID
81771
Acronym
COSI BAIR
Status last verified
Feb 2023
First submitted
22 Dec 2021
Last updated
9 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: At the time of article publication, the following will be made available long-term for use by future researchers from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept MCRI's conditions for access: * Individual participant data that underlie the results reported in this article after deidentification (text, tables, figures and appendices), and * Trial protocol, PICF, analytic code We may share the information and samples we collect with other researchers within Australia and/or overseas to increase our understanding of COVID-19 and COVID-19 vaccination and other infections. The location of data/samples sent overseas is not yet determined. Data and samples would be sent identifiable only by a study number so that the child's identity is not disclosed to these researchers. Any data or samples sent to researchers outside of Australia will not be covered by Australian regulations.

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.

    PubMed 31990350
  • 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.

    PubMed 29415180
  • 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.

    PubMed 34146093
  • 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.

    PubMed 31843845
  • 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.

    PubMed 31153688
  • 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.

    PubMed 34309859

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Tozinameran in people with COVID-19 and Vaccine Reaction, run by Murdoch Childrens Research Institute at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean change from baseline of in vitro whole blood stimulation cytokine responses to COVID-19 specific and heterologous stimulants (time frame: Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05168709, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2023.

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