Determining Reactogenicity and Immunogenicity of Delayed COVID-19 Vaccine Schedule in Children

Study Overview
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Brief Summary
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COVID-19 vaccine response data in children 5 to 11 years old remain scarce. Our understanding of the safety and immune responses including humoral and cellular responses generated in children remains limited. Safety of the vaccine is critical in the risk benefit assessment of vaccination in young children. Available data show a trend for increased risk of myocarditis after second dose, especially in males and younger age groups. It is unknown if reduced antigen dose will alter this risk in 5y to <12y age group. Reassuringly, data from early roll-out in the USA have not reported any safety signals to date. Alternate (reduce dosing or delayed dosing) strategies could help ensure maximum protection with reduced risk of side-effects. There is currently no data available to inform how long protection would last in the reduced dose or delayed dosing strategy. The trial will inform the potential use of alternate dosing schedules such as single dose or delayed dose to minimise risk and maximise benefit of COVID-19 vaccination in children 5 to 11 years old.

Detailed Description
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BNT162b2 (Pfizer-BioNTech/Comirnaty®) vaccine is a mRNA vaccine that is (26/11/2021) approved for use in adults and adolescents (12 years old and above) under the Pandemic Special Access Route (PSAR) by the Health Sciences Authority (HSA), Singapore.1 Two doses of vaccine (30mcg) given 3 weeks apart was shown to be > 95% effective in the prevention of symptomatic COVID-19 infection.2 The latest phase 3 trial of the vaccine using a lower (10 mcg) two dose schedule (3 weeks apart) in children aged 5 to 11 year old was found to be > 90% effective. Older age groups and those with comorbidities such as obesity, diabetes mellitus, etc are at highest risk of severe COVID-19 disease. Currently, recommendations for vaccination have been extended to adolescents in Singapore as well as many countries including the USA, Israel and Ireland, in view of the high rates of infection in this age group. On 29 October 2021, the FDA authorised the use of BNT162b2 Pfizer-BioNTech/Cominarty vaccine for emergency use in children 5 to 11 years old.4 Subsequently, the CDC recommended COVID-19 vaccination of children 5 to 11 years old in the USA using intramuscular 10mcg of BNT162b2 Pfizer-BioNTech/Comirnaty®) vaccine given 3 weeks apart. A key concern regarding paediatric vaccination is a rare side effect of inflammation of the heart muscle (myocarditis) that has been observed after receipt of the second dose of BNT162b2,especially in younger age groups including adolescents and males. Centre for Disease Control (CDC), USA reported that there were 9.8 cases of myocarditis per million first doses given and this rose to 67 per million after the second dose. Most cases of myocarditis were benign and self-limiting but long-term impact remains uncertain. There are possible alternatives to a standard two dose schedule given 21 days apart which may help reduce the risk of adverse events such as myocarditis. The extended interval between doses had been shown in the UK to result in improved immunogenicity in adults. The optimum timing of such a delayed dosing schedule remains unknown in children and identifying the best timing to help delay the need for boosters in children will be useful.

Official Title
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A Single Arm Phase-IV Study to Determine Reactogenicity and Immunogenicity of Delayed COVID-19 Vaccine Schedule in Children

Conditions
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Vaccine Reaction, COVID-19, Children, Only

Intervention / Treatment
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* Biological: BNT162b2 Pfizer-BioNTech/Comirnaty


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children aged 5 to 11 years old No contraindications to mRNA COVID-19 Pfizer-BioNTech vaccines Had never received any COVID-19 vaccine before Never had previous COVID-19 infections Exclusion Criteria: Children outside the age group. Immunocompromised children. Participants with previous history of COVID-19 infection.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 10mcg of BNT162b2 (Pfizer-BioNTech/Comirnaty®)<br>10mcg of BNT162b2 (Pfizer-BioNTech/Comirnaty®) for each dose. Two doses will be given at 2 months apart between doses. | Biological: BNT162b2 Pfizer-BioNTech/Comirnaty<br>* The study will use 10mcg of BNT162b2 (Pfizer-BioNTech/Comirnaty®) for each dose. Two doses will be given at 2 months apart between doses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage neutralizing antibody levels at 2m |  | 2 Months | 
| WHO International units/ml neutralizing antibody levels at 2m |  | 2 Months | 
| Geometric mean titres (GMT) neutralizing antibody levels at 2m |  | 2 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage neutralizing antibody levels at 6m and 9 to 12m |  | 12 Months | 
| WHO International units/ml neutralizing antibody levels at 6m and 9 to 12m |  | 12 Months | 
| GMT neutralizing antibody levels at 6m and 9 to 12m |  | 12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Vaccine, Children