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Immunogenicity and Reactogenicity of the Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine (CoviBOOST 2)

Primary Purpose

Vaccine Reaction, COVID-19

Status
Active
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Comirnaty® BNT162b2 /Omicron BA.4-5 vaccine (Pfizer-BioNTech)
VidPrevtyn® Beta vaccine (Sanofi/GSK)
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Vaccine Reaction focused on measuring COVID 19, mRNA vaccines, Immunulogy, Sub-unit vaccine, Booster

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Male or female aged 18 years and over Adult in a healthy condition or with a stable health status, determined by medical history, targeted physical examination and clinical judgement of the investigator to be in stable state of health. Participants with pre-existing stable chronic medical conditions defined as condition not requiring significant change in therapy or hospitalization for worsening disease within 4 weeks from enrollment can be included at the discretion of the investigator. For women of childbearing age: a negative highly sensitive pregnancy urinary test during the inclusion visit Confirmed receipt of at least three doses of COVID-19 mRNA vaccine the last dose at least 6 months prior to study vaccine Understands and agrees to comply with the study procedures Written informed consent signed by both the participant and the investigator Subject affiliated to the French Social Security System. Exclusion Criteria: Acute febrile infection (body temperature ≥ 38.0°C) within the previous 72 hours and/or presenting symptoms suggestive of COVID-19 within the previous 28 days Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection < 3 months prior to the study vaccine dose. Immunosuppressive therapy such as corticosteroids > 10 mg prednisone equivalent/day (excluding topical preparations and inhalers) within 3 months prior to inclusion or within 6 months for chemotherapies. Treatment with immunoglobulins or other blood derivatives within 3 months prior to inclusion or scheduled administration of immunoglobulins or blood derivatives before the end of the study. Any medical condition, such as cancer, that might impair the immune response. Use of experimental immunoglobulins, experimental monoclonal antibodies or convalescent plasma is not permitted during the study. Pregnancy or breastfeeding currently ongoing History of severe adverse events following vaccine administration including anaphylactic reaction and associated symptoms such as rash, breathing problems, angioedema, and abdominal pain, or a history of allergic reaction that could be triggered by a component of the SARS-COV-2 vaccine at the time of the first vaccine injection: Any bleeding disorder considered as a contraindication to an intramuscular injection, Participation in other interventional research involving humans within 4 weeks prior to the inclusion visit, or participation in any other vaccine trial excepted for those with mid or long term follow up when vaccination was made at least 4 weeks before the injection in the study. In this case no delay is required after the end of the study participation". Subject under legal protection (e.g. guardianship)

Sites / Locations

  • CIC 1417 Cochin-Pasteur

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Comirnaty® BNT162b2 /Omicron BA.4-5 vaccine (Pfizer-BioNTech)

VidPrevtyn® Beta vaccine (Sanofi/GSK)

Arm Description

Length of use : 1 day

Length of use : 1 day

Outcomes

Primary Outcome Measures

Neutralizing antibody titers against the SARS-CoV-2 variant of most prominent public health interest and against one of the variant targeted by the vaccines
Title : Neutralizing antibody titers against the SARS-CoV-2 variant of most prominent public health interest and against one of the variant targeted by the vaccines Time Frame : 28 Days Description: There will be a coprimary endpoint : Neutralizing antibody titers against the SARS-CoV-2 variant of most prominent public health interest according to pandemic evolution (among D614G, B.1.351, Omicron sub-variants BA.4-5, BQ1.1 and XBB or another recent variant) and against one of the variant targeted by the vaccines. The two variants will be specified in the statistical analysis plan before D28 data base lock. Neutralizing antibody titers will be measured by a microneutralization technique 28 days after the booster dose.

Secondary Outcome Measures

Humoral immune response against SARS-CoV-2 variants
Neutralizing antibody titers Neutralizing antibody titers against SARS-CoV-2 D614G, and variants B.1.351, Omicron sub-variants BA.4-5, BQ1.1 and XBB (or another recent variant of prominent public health interest according to pandemic evolution), measured by a microneutralization technique. Seroresponse rate in each group. Seroresponse is defined as a 10 fold or greater rise in serum neutralization titer at each follow-up time relative to D0. ELISA: Anti-Spike IgG levels expressed as BAU/mL, according to WHO recommendations. LUMINEX: Antibodies to CTD domain of the SARS-CoV-2 N protein to detect recent natural infections. Full length Spike protein expressed as BAU/mL) Antibodies to RBD of Wuhan, B.1.1.7, B.1.617.2, B.1.351, Omicron BA.1/2/5, BQ1.1, XBB and others variants according to pandemic evolution.
Number and intensity of local and systemic adverse
Number and intensity of local and systemic adverse events of any degree occurring up to day 7 after administration of the booster dose (assessed from the list of solicited adverse events); number and intensity of unsolicited clinical events up to 28 days
Factors of interest
Factors of interest are age, gender, previous SARS-COV-2 infection, time interval between the last dose of vaccine and the booster dose, and vaccine boost type
Cellular immune response
ELISpot IFN-IL-2 CD4 and CD8 response at D0 and D15 (ancillary study) against B1.351, BA.5, BQ1.1, XBB.1 ; Repertoire analysis of Memory Spike specific B cells and early ASC response at D0, D7 and M3.
Number of Covid 19 cases
Number of Covid 19 cases (symptomatic with PCR or Ag positive tests, or asymptomatic with anti NP antibodies increase from D7 to M12)

Full Information

First Posted
February 28, 2023
Last Updated
June 28, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
IREIVAC/COVIREIVAC Network
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1. Study Identification

Unique Protocol Identification Number
NCT05749926
Brief Title
Immunogenicity and Reactogenicity of the Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine
Acronym
CoviBOOST 2
Official Title
Immunogenicity and Reactogenicity of the Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine: A Non-inferiority Multicenter Single-blinded, Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 16, 2023 (Actual)
Primary Completion Date
July 12, 2023 (Anticipated)
Study Completion Date
July 12, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
IREIVAC/COVIREIVAC Network

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The objective of this trial is to compare the immunogenicity and the safety of the Beta-variant recombinant protein booster vaccine (VidPrevtyn® Beta, Sanofi) to a bivalent mRNA vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in adults previously vaccinated with at least 3 doses of COVID-19 mRNA vaccine. The results will provide important data for the future COVID 19 vaccine strategy. A biobank will also be set up to evaluate the protection conferred by one or other of these vaccines as booster in the event of the emergence of new variants in the future.
Detailed Description
The efficacy of COVID 19 vaccines for reducing the risk of severe COVID-19 infection is demonstrated in real life. However, data currently available on the persistence of immunity after vaccination on the one hand and the emergence of viral variants with reduced sensibility to vaccine immunity on the other, raise the need to administer boosters to maintain the protection and to compare different strategies as bivalent mRNA vaccines but also others platforms. The vaccines currently recommended as boosters in France are mRNA bivalent vaccines, adapted to better match the circulating variants of SARS-CoV-2 and expected to provide broader protection against Omicron sub variants (19). However, the rapid antigenic evolution of SARS-CoV-2 and the antigenic imprinting against the initial Hu-1 strain could reduce their effectiveness. More recently, the Beta-variant recombinant protein booster vaccine (VidPrevtyn Beta, Sanofi) obtained European authorization and is recommended in France as booster as an alternative to the bivalent mRNA vaccines (21, 22). However, in the absence of comparative data with the bivalent mRNA vaccines, VidPrevtyn Beta is recommended as second line. It has been shown with vectored vaccines that a heterologous vaccination scheme could be more immunogenic than a homologous scheme (23). Our group previously showed that VidPrevtyn Beta, administered as a third vaccine dose, induces higher immune response than the mRNA BNT162b2 vaccine (Comirnaty, BioNTech-Pfizer), against Beta variant but also others variants of concern (VOC) including Omicron BA1 (20) and Omicron BA4/5 (data submitted for publication). The data available at 3 and 6 months after the boost, show that VidPrevtyn Beta could be also of interest in term of durability of the response (data not published). The hypothesis is that a Beta variant protein recombinant vaccine could enlarge the protection against the variants by overpassing antigenic imprinting and the adjuvant improve the duration of immune response and protection. Moreover, the Beta-variant recombinant protein vaccine could bring an advantage in terms of reactogenicity, acceptability, cost and accessibility. In this context, as recently pointed by the HAS, comparative data on immunogenicity and reactogenicity between a bivalent mRNA vaccine and the Beta-variant recombinant protein, both administered as boosters, are needed to better adapt the COVID 19 vaccine recommendations for the future. This study is Comparative, non-inferiority, single-blinded, multicenter, randomized trial. Randomization in a 1:1 ratio, will be stratified by age (18-60 years and ≥ 60 years of age) and history of SARS-CoV-2 infection

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vaccine Reaction, COVID-19
Keywords
COVID 19, mRNA vaccines, Immunulogy, Sub-unit vaccine, Booster

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
248 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Comirnaty® BNT162b2 /Omicron BA.4-5 vaccine (Pfizer-BioNTech)
Arm Type
Active Comparator
Arm Description
Length of use : 1 day
Arm Title
VidPrevtyn® Beta vaccine (Sanofi/GSK)
Arm Type
Experimental
Arm Description
Length of use : 1 day
Intervention Type
Biological
Intervention Name(s)
Comirnaty® BNT162b2 /Omicron BA.4-5 vaccine (Pfizer-BioNTech)
Intervention Description
A single administration of COVID-19 vaccine will be performed at D0, depending on randomization
Intervention Type
Biological
Intervention Name(s)
VidPrevtyn® Beta vaccine (Sanofi/GSK)
Intervention Description
A single administration of COVID-19 vaccine will be performed at D0, depending on randomization
Primary Outcome Measure Information:
Title
Neutralizing antibody titers against the SARS-CoV-2 variant of most prominent public health interest and against one of the variant targeted by the vaccines
Description
Title : Neutralizing antibody titers against the SARS-CoV-2 variant of most prominent public health interest and against one of the variant targeted by the vaccines Time Frame : 28 Days Description: There will be a coprimary endpoint : Neutralizing antibody titers against the SARS-CoV-2 variant of most prominent public health interest according to pandemic evolution (among D614G, B.1.351, Omicron sub-variants BA.4-5, BQ1.1 and XBB or another recent variant) and against one of the variant targeted by the vaccines. The two variants will be specified in the statistical analysis plan before D28 data base lock. Neutralizing antibody titers will be measured by a microneutralization technique 28 days after the booster dose.
Time Frame
28 Days
Secondary Outcome Measure Information:
Title
Humoral immune response against SARS-CoV-2 variants
Description
Neutralizing antibody titers Neutralizing antibody titers against SARS-CoV-2 D614G, and variants B.1.351, Omicron sub-variants BA.4-5, BQ1.1 and XBB (or another recent variant of prominent public health interest according to pandemic evolution), measured by a microneutralization technique. Seroresponse rate in each group. Seroresponse is defined as a 10 fold or greater rise in serum neutralization titer at each follow-up time relative to D0. ELISA: Anti-Spike IgG levels expressed as BAU/mL, according to WHO recommendations. LUMINEX: Antibodies to CTD domain of the SARS-CoV-2 N protein to detect recent natural infections. Full length Spike protein expressed as BAU/mL) Antibodies to RBD of Wuhan, B.1.1.7, B.1.617.2, B.1.351, Omicron BA.1/2/5, BQ1.1, XBB and others variants according to pandemic evolution.
Time Frame
Day0, Day15, Day28, 3 Months, 6 Months and 12 Months
Title
Number and intensity of local and systemic adverse
Description
Number and intensity of local and systemic adverse events of any degree occurring up to day 7 after administration of the booster dose (assessed from the list of solicited adverse events); number and intensity of unsolicited clinical events up to 28 days
Time Frame
7 and 28 days
Title
Factors of interest
Description
Factors of interest are age, gender, previous SARS-COV-2 infection, time interval between the last dose of vaccine and the booster dose, and vaccine boost type
Time Frame
Day 0
Title
Cellular immune response
Description
ELISpot IFN-IL-2 CD4 and CD8 response at D0 and D15 (ancillary study) against B1.351, BA.5, BQ1.1, XBB.1 ; Repertoire analysis of Memory Spike specific B cells and early ASC response at D0, D7 and M3.
Time Frame
Day 0, Day 7, Day 15, Month 3
Title
Number of Covid 19 cases
Description
Number of Covid 19 cases (symptomatic with PCR or Ag positive tests, or asymptomatic with anti NP antibodies increase from D7 to M12)
Time Frame
Day 7 up to Month 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male or female aged 18 years and over Adult in a healthy condition or with a stable health status, determined by medical history, targeted physical examination and clinical judgement of the investigator to be in stable state of health. Participants with pre-existing stable chronic medical conditions defined as condition not requiring significant change in therapy or hospitalization for worsening disease within 4 weeks from enrollment can be included at the discretion of the investigator. For women of childbearing age: a negative highly sensitive pregnancy urinary test during the inclusion visit Confirmed receipt of at least three doses of COVID-19 mRNA vaccine the last dose at least 6 months prior to study vaccine Understands and agrees to comply with the study procedures Written informed consent signed by both the participant and the investigator Subject affiliated to the French Social Security System. Exclusion Criteria: Acute febrile infection (body temperature ≥ 38.0°C) within the previous 72 hours and/or presenting symptoms suggestive of COVID-19 within the previous 28 days Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection < 3 months prior to the study vaccine dose. Immunosuppressive therapy such as corticosteroids > 10 mg prednisone equivalent/day (excluding topical preparations and inhalers) within 3 months prior to inclusion or within 6 months for chemotherapies. Treatment with immunoglobulins or other blood derivatives within 3 months prior to inclusion or scheduled administration of immunoglobulins or blood derivatives before the end of the study. Any medical condition, such as cancer, that might impair the immune response. Use of experimental immunoglobulins, experimental monoclonal antibodies or convalescent plasma is not permitted during the study. Pregnancy or breastfeeding currently ongoing History of severe adverse events following vaccine administration including anaphylactic reaction and associated symptoms such as rash, breathing problems, angioedema, and abdominal pain, or a history of allergic reaction that could be triggered by a component of the SARS-COV-2 vaccine at the time of the first vaccine injection: Any bleeding disorder considered as a contraindication to an intramuscular injection, Participation in other interventional research involving humans within 4 weeks prior to the inclusion visit, or participation in any other vaccine trial excepted for those with mid or long term follow up when vaccination was made at least 4 weeks before the injection in the study. In this case no delay is required after the end of the study participation". Subject under legal protection (e.g. guardianship)
Facility Information:
Facility Name
CIC 1417 Cochin-Pasteur
City
Paris
ZIP/Postal Code
75679
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
The IPD will not be share. The 2 vaccines used in this study are marketed vaccine and used in routine care.

Learn more about this trial

Immunogenicity and Reactogenicity of the Beta-variant Recombinant Protein Booster Vaccine (VidPrevtyn Beta, Sanofi) Compared to a Bivalent mRNA Vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer) in Adults Previously Vaccinated With at Least 3 Doses of COVID-19 mRNA Vaccine

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