Immunogenicity and Reactogenicity Following a Booster Dose of COVID-19 mRNA Vaccine (Pfizer-BioNtech) and Two Adjuvanted Sub-unit Vaccines (SP/GSK) Administered in Adults Who Received 2 Doses of Pfizer-BioNTech mRNA Vaccine as a Primary Vaccination — COVIBOOST  

COVID-19 Clinical Trial

Official title: Immunogenicity and Reactogenicity Following a 3rd Dose of COVID-19 mRNA Vaccine (Pfizer-BioNtech) and Two Adjuvanted Sub-unit Vaccines (SP/GSK) Administered as a Booster in Adults Who Received 2 Doses of Pfizer-BioNTech mRNA Vaccine as a Primary Vaccination: A Randomized, Single-blinded Multicenter Clinical Trial

Status Active, not recruiting

Clinical Trial Summary

The vaccination campaign in France began in early 2021 and was declared mandatory for all French people in July 2021. The efficacy of COVID-19 vaccines has since been widely demonstrated, as well as their safety, and now 60% of the adult population in France has received a first dose, most of them with Pfizer-BioNTech's mRNA vaccine.

However, despite the increasing coverage, new data highlight the need for a booster dose for the most vulnerable people, including patients with immune deficiency. This makes it likely that a booster dose will also be needed in the general population, especially among healthcare workers, due to the active circulation of new variants since the beginning of summer 2021 and evidence of reduced protection against them.

On the other hand, in addition to evaluating the potential benefit of a booster vaccination, it appears interesting to also evaluate a heterologous vaccination regimen, i.e. a booster with a different vaccine than the one used for the primary vaccination. Some studies have already evaluated a two-dose heterologous regimen and the results have shown stronger protection against SARS-CoV-2. In addition, this alternative could provide a real benefit in terms of accessibility, cost, and acceptability.

The vaccine developed by Sanofi-Pasteur is based on a traditional recombinant protein approach using GSK's AS03 adjuvant. Two formulations of this vaccine are currently under development, the first targeting the S protein of the D614 strain (Wuhan strain), the second targeting the B.1.351 variant. Their value as a booster needs to be evaluated.

The objective of this trial is therefore to evaluate the immunological response and safety induced by a homologous vaccine booster (Pfizer-BioNTech vaccine booster) and a heterologous vaccine booster (one of the two experimental Sanofi/GSK vaccines booster), on the D614 (Wuhan) strain and on the SARS-CoV-2 variants.

Clinical Trial Description

The efficacy of COVID 19 vaccines for reducing the risk of severe COVID-19 infection has now been demonstrated in real life. In France, the vaccination campaign started on December 27th, 2020 and was launched rapidly for healthcare professionals and for individuals at risk of severe COVID on January 2021. On August 5th 30th, 2021, approximately 60% of the population (> 12 years) had already received complete vaccination. Out of approximately 74,3 million doses of vaccine administered, 58 million doses are Pfizer BioNTech vaccine (78%).

Data currently available on the persistence of immunity on the one hand and the appearance of viral variants with reduced sensitivity to vaccine immunity on the other, raise the need to administer further additional dose at an interval from the primary vaccination that remains to be defined, possibly different according to age and co-existing diseases.

Currently, the only data published are related to the administration of a third dose (booster) of the same vaccine as the one used for primary vaccination. However, some vaccines developed more recently could be an interesting alternative for booster dose in terms of reactogenicity, availability, cost and acceptance. Moreover heterologous vaccination could be more immunogenic than homologous scheme.

The vaccine developed by Sanofi Pasteur is based on a conventional adjuvanted recombinant protein approach. Two prototype vaccines are under development, one based on the Spike protein of the SARS CoV-2 D614 strain, the other on the B.1.351 strain. Their interest as booster vaccines needs to be investigated.

The objective of this trial is to assess the response induced by a booster dose of either recombinant protein-based subunit vaccine (targeting D614 strain or B.1.351 strain) or by a booster dose of Pfizer-BioNTech mRNA vaccine (targeting Wuhan strain) in individuals previously vaccinated with 2 doses of Pfizer-BioNTech mRNA vaccine. These results will provide important information for booster vaccination recommendations.

Participants enrolled will be healthy adults with no medical history of COVID-19; they will be recruited in 10(15?) centers in mainland France, via the COVIREIVAC network.

The study will be a randomized, single-blinded, multicentre trial with three parallel arms:

ARM 1 receiving Pfizer-BioNTech vaccine

• Group 1.A: 18-64 years old

• Group 1.B: 65 years and older

ARM 2 receiving SP/GSK subunit D614 vaccine

• Group 2.A: 18-64 years old

• Group 2.B: 65 years and older

ARM 3 receiving SP/GSK subunit B.1.351 vaccine

• Group 3.A: 18-64 years old

• Group 3.B: 65 years and older

Participants will undergo 5 visits :

• V1 (D0): inclusion, randomization, pregnancy test, PCR test, blood draw and administration of the booster dose

• V2 (D28): follow-up visit with a review of solicited and unsolicited local and systemic reactions that occurred since the last visit, and blood draw

• V3 (D90): follow-up visit with review of potential adverse events and blood draw

• V4 (D180): follow-up visit with review of potential adverse events and blood draw

• V5 (D365): follow-up visit with review of potential adverse events and blood draw

Blood samples will be used to conduct immunological analyses, and cellular analyses for a sub-category of 26 participants per group. ;

Related Conditions & MeSH terms

• COVID-19
• Vaccine Reaction

• NCT number: NCT05124171
• Study type: Interventional
• Source: Assistance Publique - Hôpitaux de Paris
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 8, 2021
• Completion date: December 2022