Covid-19 Vaccination in Adolescents and Children (COVAC)

To Compare the Reactogenicity and Immunogenicity of Recommended COVID-19 Vaccines in Young Adolescents and Children in Hong Kong

Objectives To assess the reactogenicity, measure the adaptive immune responses and track the long-term immune memory in healthy children and adults as well as pediatric patients receiving the COVID-19 vaccines-BNT162b2, CoronaVac-chosen by the Hong Kong Government; to compare the reactogenicity and immunogenicity across the vaccines used for these children and adults.

Hypothesis to be tested The safety profile and the magnitude and durability of immune responses to the COVID-19 vaccines in children are non-inferior to those in adults.

Design and subjects A single-site, comparative nonrandomised clinical trial for 450 healthy individuals or patients under 18 years old and one or both healthy parents and unrelated adults to receive one of COVID-19 vaccines by intramuscular injection (and intradermal injection)

Instruments Mobile app for subjects to record adverse effects, enzyme-linked immunosorbent assay, plaque reduction neutralization assay, luciferase immunoprecipitation system assay and flow cytometry.

Interventions BNT162b2 and CoronaVac, by intramuscular or intradermal route

Main outcome measures Types and frequencies of adverse effects within 7 days, and changes and peaks of antibody levels and antigen-specific memory T cell responses for 3 years.

Study Overview

• Status: Active, not recruiting
• Conditions: Covid19
• Intervention / Treatment: Biological: Tozinameran; Biological: CoronaVac; Biological: CoronaVac, intradermal

• Study Type: Interventional
• Enrollment (Actual): 1018
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hong Kong
    • Hong Kong, Hong Kong, China
      • Queen Mary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. informed consent from the parents or a legally acceptable representative for an underage participant
2. biological parents of students enrolled in the trial or unrelated healthy adults
3. ability to adhere to the follow-up schedules
4. willingness to report reactogenicity daily for 7 days post dose 1, 2 and 3 (and 4) proactively
5. willingness to receive that vaccine available for that particular recruitment period (as student-parent pair, if applicable)
6. good past health, including pre-existing clinically stable disease, such as paediatric or immune disorders
7. prior COVID-19 (for COVID-19 survivor subgroup)

Exclusion Criteria:

1. reported pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BNT162b2 (adult/adolescent); BNT162b2, tozinameran by Fosun/BioNTech Intramuscular injection (or intradermal for immunocompromised patients; or by graded challenge with history of non-severe allergy to PEG-containing drugs) 30ug/0.3ml per dose 3 doses, or 4 for immunocompromised patients; or 1/2 dose for patients with prior COVID-19	Biological: Tozinameran; mRNA vaccine developed by BioNTech against COVID-19; Other Names: BNT162b2
Experimental: CoronaVac (intramuscular); CoronaVac by SinoVac Intramuscular injection 3ug/0.5ml per dose 3 doses, or 4 for immunocompromised patients; or 1/2 dose for patients with prior COVID-19	Biological: CoronaVac; Inactivated virus vaccine developed by SinoVac against COVID-19, intramuscular
Experimental: CoronaVac (intradermal); CoronaVac by SinoVac Intradermal injection 3ug/0.5ml per dose 3 doses, or 4 for immunocompromised patients; or 1/2 dose for patients with prior COVID-19	Biological: CoronaVac, intradermal; Inactivated virus vaccine developed by SinoVac against COVID-19, intradermal
Experimental: BNT162b2 (paediatric); BNT162b2, tozinameran by Fosun/BioNTech Intramuscular injection (for immunocompromised patients only) 10ug/0.1ml per dose 4 doses for immunocompromised patients	Biological: Tozinameran; mRNA vaccine developed by BioNTech against COVID-19; Other Names: BNT162b2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse reactions	Percentage of occurrence, types, duration and severity of adverse reactions occurring within 7 days	7 days post-doses 1, 2 and 3 (and 4)
Binding antibody response	Geometric mean levels of SARS-CoV2 S and S-RBD-specific binding antibody and related markers as determined by Enzyme-linked Immunosorbent Assay	1 month post-dose 1, and 1, 6, 18, and 36 months post-dose 3 (and 2 weeks after dose 4)
Neutralizing antibody response	Geometric mean levels and geometric mean fold rise of SARS-CoV2 neutralizing antibodies as determined by plaque reduction neutralization assay and surrogate assays	1 month post-dose 1, and 1, 6, 18, and 36 months post-dose 3 (and 2 weeks after dose 4)
T cell response	Geometric mean percentage of CD4 and CD8 T cells specific to SARS-CoV2 S (and N and M) protein	1 month post-dose 1, and 1, 6, 18, and 36 months post-dose 3 (and 2 weeks after dose 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaccine breakthrough	Incidence of COVID-19 in participants throughout study period as self-reported or as determined by Luciferase Immunoprecipitation Systems assay/ELISA	Throughout the study period, until 36 months post-dose 3/4
Adverse events	Percentage of occurrence, types, duration and severity of adverse events and severe adverse events throughout study period	Throughout the study period, until 36 months post-dose 3/4
Binding anti-N antibody response	Geometric mean levels and geometric mean fold rise of SARS-CoV2 N-specific binding antibody as determined by Enzyme-linked Immunosorbent Assay in Arm C participants receiving CoronaVac	1 month post-dose 1, and 1, 6, 18, and 36 months post-dose 3 (and 2 weeks after dose 4)

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Investigators: Principal Investigator: Yu Lung Lau, MD, The University of Hong Kong

Publications and helpful links

General Publications

• Rosa Duque JS, Wang X, Leung D, Cheng SMS, Cohen CA, Mu X, Hachim A, Zhang Y, Chan SM, Chaothai S, Kwan KKH, Chan KCK, Li JKC, Luk LLH, Tsang LCH, Wong WHS, Cheang CH, Hung TK, Lam JHY, Chua GT, Tso WWY, Ip P, Mori M, Kavian N, Leung WH, Valkenburg S, Peiris M, Tu W, Lau YL. Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents. Nat Commun. 2022 Jun 28;13(1):3700. doi: 10.1038/s41467-022-31485-z. Erratum In: Nat Commun. 2022 Aug 15;13(1):4798.

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2021
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: March 1, 2021
• First Submitted That Met QC Criteria: March 15, 2021
• First Posted (Actual): March 16, 2021

Study Record Updates

• Last Update Posted (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: COVAC01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No