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

NCT05168709 | Completed Phase 4 DMC

• 1 other identifier: 81771
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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. 1.Day 0 - baseline (day of COVID-19 vaccination #1), and
2. 2.Day 84 (28 days after COVID-19 vaccination #2).

Conditions

COVID-19; Vaccine Reaction; Immunization; Infection

Keywords

Non-specific effects; COVID-19 vaccination; paediatric vaccination; heterologous immunity; mRNA vaccine

Outcome Measures

Primary Outcomes (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

  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)

• Mean change from baseline of anti-SARS-CoV-2 antibody titres

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

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

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

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

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

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

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

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

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

Study Arms (1)

Approved COVID-19 vaccination

EXPERIMENTAL

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.

Biological: Tozinameran

Interventions

Tozinameran BIOLOGICAL

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)

Also known as: COMIRNATY, BNT162b2 [mRNA], Pfizer COVID-19 Vaccine

Approved COVID-19 vaccination

Eligibility Criteria

• Age: 5 Years - 11 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead

Study Sites (1)

Melbourne Children's campus

Parkville, Victoria, 3052, Australia

Location

Related Publications (6)

• 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.

  PMID: 31990350 BACKGROUND

• 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.

  PMID: 29415180 BACKGROUND

• 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.

  PMID: 34146093 BACKGROUND

• 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.

  PMID: 31843845 BACKGROUND

• 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.

  PMID: 31153688 BACKGROUND

• 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.

  PMID: 34309859 BACKGROUND

Related Links

• MIS BAIR trial website. Participants for COSI BAIR will be recruited from this trial population.

MeSH Terms

Conditions

COVID-19; Infections

Interventions

BNT162 Vaccine; RNA, Messenger

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors; RNA; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Nigel Curtis

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 22, 2021
• First Posted: December 23, 2021
• Study Start: January 20, 2022
• Primary Completion: September 29, 2022
• Study Completion: September 29, 2022
• Last Updated: February 9, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: Following the completion and analysis of the trial, the data will be retained long-term following the mandatory archive period for use in future research projects. The retention period will be for at least 15 years post-trial completion or until the child is aged 25 years (whichever is later). The Sponsor-Investigator and/or delegate will be the custodians during the archive period. Following the end of the archival period, the data will be disposed of.
• Access Criteria: * Must pertain to ethically approved research * Must be from a recognised institution * Must be willing to share the aims, outcomes and outcomes measures of the secondary analyses * Must ask for consent from the COSI BAIR principal investigators * Must be approved by the COSI BAIR Sponsor-Investigator

Locations

AU (1)