Trial NCT05057169
Publication Leung N, medRxiv, 2022
Dates: 2021-11-12 to 2022-01-27
Funding: Public/non profit (This project was supported by the Health and Medical Research Fund, Theme-based Research Scheme of the Research Grants Council of the Hong Kong Special Administrative Region, China. BJC is supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, and a RGC Senior Research Fellow Scheme grant from the Research Grants Council of the Hong Kong Special Administrative Region, China. The funding bodies had no role in the design of the study, the collection, analysis, and interpretation of data, or writing of the manuscript.)
Conflict of interest: Yes

Methods
RCT
Location : Multicenter / Hong Kong (China)
Follow-up duration (months): 5
3 mcg/600 SU CoronaVac homologous (n = 178)
3 mcg/600 SU CoronaVac heterologous (n = 202)
30 mcg BNT162b2 homologous (n = 204)
30 mcg BNT162b2 heterologous (n = 186)
Inclusion criteria
  • Hong Kong residents
  • ≥18 years of age at enrolment
  • had previously received a homologous two-dose primary series of either BNT162b2 or CoronaVac, with the second dose received at least 6 months (180 days) earlier
  • Agreement to refrain from blood donation during the course of the study
  • Willing to provide blood samples for all the required time points
  • The individual or their caregiver have a home phone or cellular or mobile phone for communications purpose
  • Capable of providing informed consent.
Exclusion criteria
  • History of confirmed SARS-CoV-2 infection
  • a delay of ≥43 days between the first two vaccine doses
  • use of medication that could impair the immune system in the last 6 months (except topical steroids or short-term oral steroids)
  • use of immunoglobulins and/or any blood products within 90 days prior to enrolment
  • pregnant or nursing, or planning to become pregnant
  • Have previously already received one or two doses of any COVID-19 vaccines except CoronaVac or BNT162b2, for example but not limited to BBIBP-CorV (inactivated vaccine, Sinopharm), AZD1222 (adenovirus vector-based vaccine, Oxford/AstraZeneca), Sputnik V (adenovirus vector-based vaccine, Gamaleya Research Institute) and Ad26.COV2.S (adenovirus vector-based vaccine, Johnson & Johnson)
  • Individuals who report any medical condition, or as determined by a clinician, not suitable to receive mRNA or inactivated COVID-19 vaccines, including but not limited to allergies to the active substance or other ingredients of the vaccine
  • Currently with diagnosed medical conditions related to their immune system.
Interventions
Intervention
1 IM dose of 3 mcg (600 SU) CoronaVac (booster), at least 6 months (median 226 days) after 2-dose prime vaccination with BNT162b2.
1 IM dose of 30 mcg of BNT162b2 (booster), at least 6 months (median 222 days) after 2-dose prime vaccination with BNT162b2.
1 IM dose of 30 mcg of BNT162b2 (booster), at least 6 months (median 236 days) after 2-dose prime vaccination with CoronaVac.
Control
1 IM dose of 3 mcg (600 SU) CoronaVac (booster), at least 6 months (median 236 days) after 2-dose prime vaccination with CoronaVac.
Participants
Randomized
770 participants
Characteristics of participants
Type of participants: Adults including co-morbidities
N=770
230 males
Children: 0
Pregnant women: 0
Immunocompromized patients: 0
Mean age:
Age range: NR
Description of participants
Adults including co-morbidities that were HIV-negative with no history of COVID-19 infection and who had previously completed CoronaVac or BNT162b2 primary schedules in multiple centres in Hong Kong (China).
Primary outcome
In the register
Geometric mean titer (GMT) of SARS-CoV-2 serum neutralizing antibodies [Time Frame: 28 days after vaccination]: The primary outcome measure is the vaccine (humoral) immunogenicity at 28 days after the booster dose, measured as geometric mean titer (GMT) of SARS-CoV-2 serum neutralizing antibodies using plaque reduction neutralization test (PRNT).
In the report
Immunogenicity at 28 days after the third dose of either BNT162b2 or CoronaVac, measured as geometric mean titer (GMT) of SARS-CoV-2 serum neutralising antibodies using plaque reduction neutralization test (PRNT50)
Documents
available

Protocol

NR

Statistical plan

*

Data-sharing stated: Yes, Data to reproduce the results shown here will be posted on github after peer review and publication of our article.
Data accessibility: Data to reproduce the results shown here will be posted on github after peer review and publication of our article. Corresponding authors: Benjamin Cowling bcowling@hku.hk; and Nancy Leung leungnan@hku.hk
Risk of bias
Overall
The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review
Some concerns
General comment In addition to the pre-print and its supplement, the study registry was used in data extraction and risk of bias assessment. Neither protocol nor statistical analysis plan was available. Preliminary analysis, follow-up visits were scheduled up to 1 year after booster; results reported here up to 4-6 months. The target sample size specified in the registry was achieved, however, there were substantial exclusions post-randomization due to ineligibility at the confirmation screening assessment before booster. The primary outcome in the article reflects that in the registry. There is no change from the trial registration in the intervention and control treatments.