Clinical trial NCT05057182: Third Dose of mRNA Vaccination to Boost COVID-19 Immunity (mBoost Study)
Official title: mRNA Vaccination to Boost Antibodies Against SARS-CoV-2 in Recipients of Inactivated Vaccines (the "mBoost" Study)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: COVID 19 Vaccine
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2021-09-27
Enrollment: 300
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 300 adults ≥30 years of age who have previously received two doses of an inactivated COVID-19 vaccine at least 3 months earlier will receive a third dose with an mRNA vaccine (BNT162b2, BioNTech). Investigators will monitor reactogenicity and measure the immune response to the third dose.

Detailed description: Background: The accrual of population immunity to COVID-19 could allow life to return to pre- pandemic normality. Immunity can be acquired through natural infections or, preferably, by vaccination. An unprecedented global effort has succeeded in developing a number of COVID-19 vaccines. All vaccines against COVID-19 approved until now have originally been developed as either a single dose or following a homologous two-dose regimen. Inactivated COVID-19 vaccines have shown inferior immunogenicity compared to mRNA vaccines but there are no studies looking into the immunogenicity, reactogenicity and safety profile of mRNA vaccination provided as a booster dose in individuals who have previously received two doses of an inactivated COVID-19 vaccine.

Aims and Objectives: The aims of this study are: (1) to determine whether one dose of mRNA vaccine can boost neutralizing antibodies against SARS-CoV-2 in individuals who have previously received two doses of inactivated COVID-19 vaccines, and (2) to assess the reactogenicity and safety of heterologous 3rd doses of vaccination. The specific primary objective of this study is to assess the vaccine (humoral) immunogenicity, proxy by SARS-CoV-2 serum neutralizing antibody titers, of a 3rd dose dose of mRNA vaccine (using BNT162b2, Fosun/BioNTech) at 28 days after the booster dose in individuals who have previously received two doses of any inactivated COVID-19 vaccines.

Study design: Open label trial in adults aged 30 years of age or older (at enrolment). The duration of participation for each participant will be 12 months from the administration of the 3rd vaccine dose. The immune response and reactogenicity of one dose of BNT162b2 will be investigated in individuals who previously received two doses of any inactivated COVID-19 vaccines at least 3 months earlier. Participants will be enrolled shortly before receiving the booster dose of BNT162b2 (day 0), with blood collection at days 0, 28, 182 and 365 days after enrolment for analysis of humoral immune responses.

Main outcomes: The primary outcome is the vaccine immunogenicity measured as SARS-CoV-2 serum neutralizing antibodies in individuals who previously received two doses of any inactivated COVID-19 vaccines, evaluated as the geometric mean titer (GMT) at 28 days after the 3rd dose. The secondary outcomes include (1) a comparison of SARS- CoV-2 serum neutralizing antibodies as the geometric mean fold rise from baseline to each post-vaccination timepoint (i.e. at days 28, 182 and 365), and (2) descriptive analysis of the reactogenicity and safety profile of the 3rd dose.

Target population: Adults aged 30 years or older

Number of Subjects Planned: 300 participants to be recruited between September 2021 and December 2021

Study duration: 12 months for each participant

Potential implications: This study will provide important evidence into the effects of using a 3rd dose of mRNA vaccines to boost the immune response in individuals that had previously received two doses of inactivated vaccines. This information together with data collected on reactogenicity and safety could inform COVID-19 vaccination policy locally and internationally.

Eligibility criteria: Inclusion Criteria:

* Aged 30 years or older at enrolment.
* Have received two doses of any inactivated COVID-19 vaccines (for example Sinovac- CoronaVac, Sinopharm-BIBP) with the most recent dose at least 90 days prior to enrolment.
* Currently resident and planning to remain resident in Hong Kong during the duration of the study, i.e. for 12 months after enrolment.
* 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:

* A history of laboratory-confirmed or clinically confirmed COVID-19 infection. Have received (at least one dose of) any COVID-19 vaccines other than inactivated vaccines.
* Individuals who report any medical condition, or as determined by a clinician, not suitable to receive mRNA vaccines, including but not limited to allergies to the active substance or other ingredients of the vaccine.
* With diagnosed medical conditions related to their immune system.
* Use of medication that impairs immune system in the last 6 months, except topical steroids or short-term oral steroids (course lasting ≤ 14 days).
* Have used immunoglobulins and/or any blood products within 90 days prior to enrolment (administration of the study vaccine).
* Pregnancy, lactation or intention to become pregnant in the coming 3 months.

Primary outcomes:
measure: Geometric Mean Titer of SARS-CoV-2 serum neutralizing antibodies
timeFrame: 28 days after vaccination
Secondary outcomes:
measure: Geometric Mean Titer of SARS-CoV-2 serum neutralizing antibodies
timeFrame: 182 and 365 days after vaccination
measure: The geometric mean fold rise (GMFR) of SARS-CoV-2 serum neutralizing antibody titers from baseline to each post-vaccination timepoint measured.
timeFrame: Day 28, 49, 182 and 365 after vaccination
measure: Reactogenicity
timeFrame: 7 days after vaccination or until the last symptom disappears
measure: Hospitalizations from any cause
timeFrame: 365 days after vaccination
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong
Study officials:
affiliation: The University of Hong Kong
name: Benjamin J Cowling, PhD
role: PRINCIPAL_INVESTIGATOR
References: