Efficacy, Immunogenicity and Safety of Inactivated Vaccine (Coronavac) Against SARS-COV2 in Children and Adolescents

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of vaccinating children and adolescents, aged 3 to 17 years, with a two-dose schedule of the inactivated vaccine (Coronavac) against SARS-Cov-2.

Detailed Description
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Nine hundred sixty (960) participants will be randomized into 2 groups, in a 2:1 ratio, to receive the inactivated Coronavac/Butantan vaccine (VACC, N=640) and a group to receive the immunizing BNT162b2 (Pfizer) (BNTC, N=320). The VACC group will also be compared to a group of adults aged 18 to 49 who received Coronavac (ADU, N=160). The main outcome will be the geometric title of neutralizing antibodies and the secondary outcomes will be the incidence of the number of cases confirmed by RT-PCR, the cellular immune response and frequency of adverse events. Outcomes will be evaluated before the first dose, and 28 and 90 days after the second dose, and followup after 6 and 12 months. The study hypothesis is that the cellular and humoral immune response of children and adolescents is not inferior to the age group 18 to 49 years, who received Coronavac and compared to children vaccinated with the immunizing BNT162b2 (Pfizer) and that the inactivated vaccine presents lower reactogenicity for the age group studied.

Official Title
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Efficacy, Immunogenicity and Safety of Inactivated Vaccine (Coronavac) Against SARS-COV2 in Children and Adolescents - Curumim Project

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Inactivated Coronavac/Butantan vaccine
* Biological: BNT162b2 (Pfizer)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 3 and 17 years old (VACC and BNTC groups) Age between 18 and 49 years old (ADU group) Exclusion Criteria: Pregnant teenagers; History of severe allergic reaction (anaphylaxis, urticaria or angioedema) to any previously administered vaccine; Have previously received a vaccine against COVID-19; Personal history of SARS-CoV-2-related Multisystem Inflammatory Syndrome (MIS-C); Immunosuppressed due to conditions such as inborn error of metabolism, HIV infection, neoplasia or use of immunosuppressive drugs (systemic corticosteroids for more than 14 days or another immunosuppressant).

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 49 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized into 2 groups, in a 2:1 ratio, to receive the inactivated Coronavac/Butantan vaccine (VACC) and a group to receive the immunizing BNT162b2 (Pfizer) (BNTC). The VACC group will also be compared to a group of adults aged 18 to 49 who received Coronavac (ADU).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VACC<br>This group will receive the inactivated Coronavac/Butantan vaccine. | Biological: Inactivated Coronavac/Butantan vaccine<br>* Inactivated Coronavac/Butantan vaccine in 2 doses of 0.5 ml, 4 weeks apart<br>|
| Active Comparator: BNTC<br>This group will receive the immunizing BNT162b2 (Pfizer). | Biological: BNT162b2 (Pfizer)<br>* BNT162b2 (Pfizer) vaccine in 2 doses of 0.1 ml or 0.30 ml (according to age group), 4 weeks apart<br>|
| Active Comparator: ADU<br>This group of adults participants will receive the inactivated Coronavac/Butantan vaccine. | Biological: Inactivated Coronavac/Butantan vaccine<br>* Inactivated Coronavac/Butantan vaccine in 2 doses of 0.5 ml, 4 weeks apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral neutralization assay | Neutralizing antibody titers will be expressed by the ability of antibodies to neutralize up to 50% the number of plaques (PRNT50). Title > 1:50 will be considered positive. | 3 months | 
| Chemiluminescence serological assay for qualitative and quantitative determination of neutralizing antibodies against Spike protein (anti-SARS-Cov-2 anti-IgG-S) | Results are expressed in AU/mL and data interpretation will be as follows: <50 AU/mL = negative; ≥50 U/mL = positive. | 3 months | 
| Serological assay by chemiluminescence for qualitative and quantitative determination of specific IgG antibodies against the nucleocapsid protein of SARS-Cov-2 | Results will be expressed as fluorescence intensity or pg/mL. The cutoff is 1.4 and <1.4 = negative; ≥1.4 = positive. | 3 months | 
| Dosage of systemic soluble factors | Chemokines, cytokines and growth factors - biomarkers of humoral and cellular response. Results will be expressed in pg/mL. | 12 months | 
| Antigen-specific stimulation of peripheral blood mononuclear cells in vitro | The results will be expressed as a positive percentage frequency for a given cell phenotype. | 2 months | 
| T lymphocytes | The results will be expressed as a positive percentage frequency for a given cell phenotype. | 12 months | 
| B lymphocytes | The results will be expressed as a positive percentage frequency for a given cell phenotype. | 12 months | 
| intracytoplasmic cytokines | The results will be expressed as a positive percentage frequency for a given cell phenotype. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RT-PCR confirmed cases | Cases confirmed by RT-PCR, whose signs/symptoms have started 15 days after the second dose of vaccine, over 6 months after receiving the vaccine. | 6 months | 
| Adverse events | Surveillance of adverse post-vaccine events (PVAE) and adverse events of special interest (EAIE) will be carried out. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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covid-19, Vaccine, Children, Coronavac, Vero Cell