Efficacy of Different COVID-19 Vaccine Combinations in Inducing Long-term Humoral Immunity [PRIBIVAC] — PRIBIVAC  

COVID-19 Clinical Trial

Official title: Heterologous Prime-boost-boost Vaccine Combinations for Long-term Humoral and Cellular Immunity Against COVID-19

Status Recruiting

Clinical Trial Summary

This study will assess heterologous prime-boost-boost vaccine regimens in comparison with an homologous regimen in order to compare short and long-term immunogenicity of different COVID-19 vaccine combinations against the ancestral SARS-CoV-2 as well as different variants of concern (VOCs).

Hypothesis: One or more heterologous prime-boost-boost COVID-19 vaccine combinations will produce humoral and cellular immunity that is non-inferior to an homologous prime-boost-boost vaccination against wildtype SARS-CoV-2 and/or 1≥ VOC.

Clinical Trial Description

ICOVID-19 vaccination programs worldwide have so far focused on raising population immunity through the primary COVID-19 vaccine series. In Singapore two mRNA vaccines developed by Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273), have been granted interim authorisation by Health Science Authority (HSA) under the pandemic special access route (PSAR). Some other COVID-19 vaccines are authorised by HSA for use in Singapore as part of the Special Access Route (SAR) through their addition to the WHO Emergency Use List (EUL). Many of these vaccines have been widely used in other countries, including an inactivated whole virus vaccine developed by Sinovac; an adenovirus-based formulation developed by Oxford-AstraZenaca; and a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector vaccine developed by Johnson & Johnson / Janssen.

Vaccination in Singapore started first for frontline and healthcare workers with BNT162b2 at the end of December 2020. Over the following months this vaccine program was extended first to older adults and then the general population, while mRNA-1273 was also introduced alongside BNT162b2. By August 2021 >75% of Singapore's resident population was fully vaccinated. The pivotal phase 3 clinical trials of BNT162b2 and mRNA-1273 reported a vaccine efficacy of >95% against symptomatic and severe disease. However, data from individuals vaccinated with mRNA-1273 showed gradually declining neutralising antibody titres by 6 months post inoculation. In addition, the emergence of variants of concern (VOCs) capable of evading protective immunity (from a wildtype SARS-CoV-2 virus vaccine) has raised the need for a long term COVID-19 immunisation strategy. Several fundamental questions need to be addressed in order to design this: Will a 3rd booster dose offer clinical benefit? Who needs a booster vaccination? How long after the primary series should it be administered? And, which vaccine should be used?

This study will assess the immunogenicity and safety of heterologous boost COVID-19 vaccine regimens (intervention groups 1-4) compared with a homologous boost regimen (control arm). Potential participants would have already received a homologous prime-boost vaccination with BNT162b2 or mRNA-1273 prior to randomisation. The booster vaccine for the control arm will be the homologous mRNA vaccine (e.g. BNT162b2 + BNT162b2 + BNT162b2 or mRNA-1273 + mRNA-1273 + mRNA-1273), while for individuals randomised to intervention group 1 the mRNA booster vaccine administered will be heterologous to the primary series (e.g. BNT162b2 + BNT162b2 + mRNA-1273 or mRNA-1273 + mRNA-1273 + BNT162b2).

The booster vaccine candidates for intervention arms 2-4 will be an alternative COVID-19 vaccine. This may include vaccines that have received full or interim authorisation from HSA, are available under the Special Access Route (SAR) for vaccines that are part of the WHO Emergency Use List (EUL), or are currently under clinical development.

Control group: Homologous mRNA booster vaccine Intervention group 1: Heterologous mRNA booster vaccine Intervention group 2: Non-mRNA booster vaccine A Intervention group 3: Non-mRNA booster vaccine B Intervention group 4: Non-mRNA booster vaccine C

Vaccine candidates A, B and C may enter the study at different time points, participants will be randomised at equal probability to the available intervention arms at the time of randomisation. This will reduce the risk of bias (e.g. participant preference for a certain arm) compared with a non-randomised design. An ideal scenario is to have all the selected vaccines approved prior to the start of recruitment. However, due to the unknown time of availability of vaccine candidates A, B and C, and the urgency of the current situation, recruitment to the control and intervention group 1 will start first. ;

Related Conditions & MeSH terms

• COVID-19

• NCT number: NCT05142319
• Study type: Interventional
• Source: Tan Tock Seng Hospital
• Contact: Barnaby Young, Dr
• Phone: 63577458
• Email: Barnaby_Young@ncid.sg
• Status: Recruiting
• Phase: Phase 3
• Start date: October 12, 2021
• Completion date: April 2023