Randomized, Single-blinded, Multicenter Trial Comparing the Immune Response to a 2nd Booster Dose of COVID-19 mRNA Vaccine (Pfizer-BioNTech) or Sanofi /GSK B.1.351 Adjuvanted Vaccine in Adults — COVIBOOSTAnci1  

COVID-19 Vaccines Clinical Trial

Official title: Randomized, Single-blinded, Multicenter Trial Comparing the Immune Response to a 2nd Booster Dose of COVID-19 mRNA Vaccine (Pfizer-BioNTech) or Sanofi /GSK B.1.351 Adjuvanted Vaccine in Adults Who Received 2 Doses of Pfizer-BioNTech mRNA Vaccine and a Booster Dose of Pfizer-BioNTech or Moderna mRNA Vaccine

Status Active, not recruiting

Clinical Trial Summary

The effectiveness of COVID-19 vaccines in reducing the risk of severe COVID-19 is currently demonstrated. In France, since the beginning of the vaccination campaign, 54,266,859 people have received at least one injection (ie. 80.5% of the total population), 53,354,698 people now have a complete vaccination schedule (ie. 79.1% of the total population) and since the beginning of the booster campaign, 39,558,416 people have received a 1st booster dose.

However, the 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, suggest the need to administer booster doses at variable intervals depending on age and comorbidities. Real-life efficacy data from France and around the World confirm that people who have received a booster dose are better protected than those who have only received a primary vaccination schedule (HAS).

In this context, the Ministry of Health, has pronounced on the possibility of administering a second booster dose for people aged 60 and over. Moreover, the recommendations for the Haute Autorité de Santé for the 2nd booster dose in general population should be available in June 2022.

Three vaccines, mRNA BNT162b2 vaccine, Sanofi/GSK monovalent D614 and B.1.351 formulations were administered as 1st booster in the CoviBOOST trial. All three vaccines boosted antibodies and neutralizing response after a BNT162b2 initial course. Heterologous boosting with the Sanofi/GSK SARS-CoV-2 recombinant adjuvanted protein vaccine B.1.351 (Beta formulation) provided higher rates of neutralizing antibodies against variants, including Omicron BA.1, compared with the mRNA BNT162b2 vaccine. Due to the start of the study after the beginning of booster vaccination campaign in elderly, the enrollment of participants over 65 years of age was difficult so, only 8 subjects aged 60 years and over were enrolled. As vaccine immunogenicity is lower in older populations and is waning more rapidly, it is important to evaluate the adjuvanted vaccine in this population.

The objective of this ancillary study is to compare, in participants aged of 60 years and older and previously vaccinated with 3 doses of mRNA vaccine (2 doses of Pfizer BioNTech) and a 3rd dose of Pfizer BioNTech or Moderna, the immunogenicity of a second booster dose of the B.1.351 strain recombinant protein- based subunit vaccine to BNT162b2 (mRNA Pfizer BioNTech Vaccine).These results will provide important information for booster vaccination recommendations in this age group.

Clinical Trial Description

The 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, suggest the need to administer booster doses at variable intervals depending on age and comorbidities. Real-life efficacy data from France and around the World confirm that people who have received a booster dose are better protected than those who have only received a primary vaccination schedule (HAS).

Currently available data from the United States and the United Kingdom show that the protection conferred by the first booster dose diminishes after 3 months, particularly in persons 60 years of age and older, and justified the recommendation of a second booster dose.

Data from Israel show that a second booster dose (4th dose) reduces the rate of confirmed infections by a factor of 2 and the rate of severe disease by a factor of 4. The safety data, although limited, are reassuring.

In this context, the Ministry of Health, has pronounced on the possibility of administering a second booster dose for people aged 60 and over. Moreover, the recommendations for the Haute Autorité de Santé for the 2nd booster dose in general population should be available in June 2022.

The vaccines currently recommended in France, for booster vaccination are mRNA vaccines. However, some vaccines that were developed later in the clinic could present an interesting alternative in terms of reactogenicity, accessibility, cost and acceptability. Moreover, a heterologous vaccination scheme could be more immunogenic than a homologous scheme. Therefore, it is important to be able to evaluate these vaccines as a second booster dose.

The COVID 19 vaccines developed by Sanofi are based on a classical adjuvanted recombinant protein approach. Three candidate 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, and the third is a vaccine combining the two.

Three vaccines, mRNA BNT162b2 vaccine, Sanofi/GSK monovalent D614 and B.1.351 formulations were administered as 1st booster in the CoviBOOST trial. All three vaccines boosted antibodies and neutralizing response after a BNT162b2 initial course. Heterologous boosting with the Sanofi/GSK SARS-CoV-2 recombinant adjuvanted protein vaccine B.1.351 (Beta formulation) provided higher rates of neutralizing antibodies against variants, including Omicron BA.1, compared with the mRNA BNT162b2 vaccine.

Due to the start of the study after the beginning of booster vaccination campaign in elderly, the enrollment of participants over 65 years of age was difficult so, only 8 subjects aged 60 years and over were enrolled. As vaccine immunogenicity is lower in older populations and is waning more rapidly, it is important to evaluate the adjuvanted vaccine in this population.

The objective of this ancillary study is to compare, in participants aged of 60 years and older and previously vaccinated with 3 doses of mRNA vaccine (2 doses of Pfizer BioNTech) and a 3rd dose of Pfizer BioNTech or Moderna, the immunogenicity of a second booster dose of the B.1.351 strain recombinant protein- based subunit vaccine to BNT162b2 (mRNA Pfizer BioNTech Vaccine).These results will provide important information for booster vaccination recommendations in this age.

Participants enrolled will be healthy adults of 60 years old and over they will be recruited in 15 centers in mainland France, via the COVIREIVAC network.

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

ARM 1 receiving Pfizer-BioNTech vaccine

• Group 1.A: 1rst booster Pfizer

• Group 1.B: 1rst booster Moderna

ARM 2 receiving SP/GSK subunit B.1.351 vaccine

• Group 2.A: 1rst booster Pfizer

• Group 2.B: 1rst booster Moderna

Participants will undergo 4 visits :

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

• V2 (D15): follow-up visit with a review of solicited and unsolicited local and systemic reactions that occurred since the last visit, and blood draw

• V3 (D28): follow-up visit with review of potential adverse events and blood draw

• V4 (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

Blood samples will be used to conduct immunological analyses, and cellular analyses for a sub-category of 25 participants per group. ;

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Vaccines

• NCT number: NCT05405283
• Study type: Interventional
• Source: Assistance Publique - Hôpitaux de Paris
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 8, 2022
• Completion date: July 2023