Clinical trial NCT05168709: Investigating COVID-19 Vaccine Immunity in Children in the Melbourne Infant Study of BCG for Allergy and Infection Reduction
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: COVID-19
Vaccine Reaction
Immunization; Infection
Keywords: Non-specific effects
COVID-19 vaccination
paediatric vaccination
heterologous immunity
mRNA vaccine
Lead sponsor: Murdoch Childrens Research Institute
Sponsor class: OTHER
First posted: 2021-12-23
Enrollment: 51
Sex: ALL
Minimum age (years): 5
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: BASIC_SCIENCE

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).


Eligibility criteria: 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.

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.

Primary outcomes:
measure: Mean change from baseline of in vitro whole blood stimulation cytokine responses to COVID-19 specific and heterologous stimulants
timeFrame: 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:
measure: Mean change from baseline of anti-SARS-CoV-2 antibody titres
timeFrame: Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)
measure: Mean change from baseline of SARS-CoV-2-reactive T cell responses
timeFrame: Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)
measure: Correlation of serological profiling of previous viral infections and antiviral responses, and post-vaccination anti-SARS-CoV-2 antibody titres
timeFrame: Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)
measure: Correlation of serological profiling of vaccine-preventable disease antibody responses and post-vaccination anti-SARS-CoV-2 antibody titres
timeFrame: Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)
measure: Correlation of whole blood cytokine responses to vaccine-preventable disease antigens and post-vaccination anti-SARS-CoV-2 antibody titres
timeFrame: Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)
measure: Mean change from baseline of vaccine-preventable disease antibody titres
timeFrame: Day 0 (the day of the first COVID-19 vaccine dose) to day 84 (28 days after the second COVID-19 vaccine dose)
Other outcomes:
Locations:
city: Parkville
country: Australia
facility: Melbourne Children's campus
state: Victoria
Study officials:
affiliation: Murdoch Childrens Research Institute
name: Nigel Curtis
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.