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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)

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ClinicalTrials.gov Identifier: NCT05124171
Recruitment Status : Active, not recruiting
First Posted : November 17, 2021
Last Update Posted : July 11, 2022
Sponsor:
Collaborator:
COVIREIVAC
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief 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.


Condition or disease Intervention/treatment Phase
COVID-19 Vaccine Reaction Biological: BNT162b2 Biological: CoV2 preS dTM adjuvanted vaccine (D614), Sanofi/GSK Biological: CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 247 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
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
Actual Study Start Date : December 8, 2021
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Comirnaty® (Pfizer-BioNTech)
Length of use : 1 day
Biological: BNT162b2

ARM 1 receiving Pfizer-BioNTech vaccine

  • Group 1.A: 18-64 years old
  • Group 1.B: 65 years and older
Other Name: pfzer/BioNTech, mARN vaccine,

Experimental: CoV2 preS dTM adjuvanted vaccine (D614), Sanofi/GSK
Length of use : 1 day
Biological: CoV2 preS dTM adjuvanted vaccine (D614), Sanofi/GSK

ARM 2 receiving SP/GSK subunit D614 vaccine

  • Group 2.A: 18-64 years old
  • Group 2.B: 65 years and older

Experimental: CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK
Length of use : 1 day
Biological: CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK

ARM 3 receiving SP/GSK subunit B.1.351 vaccine

  • Group 3.A: 18-64 years old
  • Group 3.B: 65 years and older




Primary Outcome Measures :
  1. rate of neutralizing antibody titers against SARS-CoV-2 D614 and B.1.351 viral strains [ Time Frame: 15 days ]
    Increased rate of at least 10 fold between D0 and D15 after the booster dose in neutralizing antibody titers against SARS-CoV-2 D614 and B.1.351 viral strains, measured by a microneutralisation technique in each group to assess the immunogenicity of a booster dose of an adjuvanted subunit vaccine (SP vaccine) as between D614 or B.1.351 and a mRNA vaccine (Pfizer BioNTech) in adults who were primarily vaccinated with 2 doses of mRNA vaccine (Pfizer BioNTech) with the 2nd dose of vaccine received at least 6 months +/- 1 month prior to the booster dose.


Secondary Outcome Measures :
  1. Rate of increase in neutralizing antibody titers against SARS-CoV-2 D614 and B.1.351 viral strains [ Time Frame: 28 days ]
    Rate of increase in neutralizing antibody titers against SARS-CoV-2 D614 and B.1.351 viral strains, measured by a microneutralisation technique between 0 and 28 days after the booster dose in each group

  2. Quantity and intensity of unsolicited local and systemic events up to 7 days [ Time Frame: 7 days ]
    Quantity and intensity of local and systemic events of any grade occurring up to 7 days after boost injection (assessed from the list of solicited adverse events)

  3. Quantity and intensity of unsolicited local and systemic events up to 28 days [ Time Frame: 28 days ]
    Quantity and intensity of local and systemic events of any grade occurring up to 28 days after boost injection (assessed from the list of solicited adverse events)

  4. Anti-Spike (D614) and anti-RBD (D614 and B.1.351) IgG levels [ Time Frame: between Month 3 and Day 0 ]
    Anti-Spike (D614) and anti-RBD (D614 and B.1.351) IgG levels, expressed in BAU/ml, according to WHO recommendations D28 after the booster dose mRNA or adjuvanted subunit vaccine

  5. Difference in anti-Spike (D614) and anti-RBD (D614 and B.1.351) IgG levels at 3 months [ Time Frame: Between Month 6 and Day 0 ]
    Difference in anti-Spike (D614) and anti-RBD (D614 and B.1.351) IgG levels between M3 and D0

  6. Difference in anti-Spike (D614) and anti-RBD (D614 and B.1.351) IgG levels at 12 months [ Time Frame: between Month 12 and Day 0 ]
    Difference in anti-Spike (D614) and anti-RBD (D614 and B.1.351) IgG levels between M12 and D0

  7. Neutralizing antibody titers against D614, alpha, gamma and delta variants at 3 months [ Time Frame: 3 months ]
    Neutralizing antibody titers against D614, alpha, gamma and delta variants at 3 months

  8. Neutralizing antibody titers against D614, alpha, gamma and delta variants at 3 months [ Time Frame: 6 months ]
    Neutralizing antibody titers against D614, alpha, gamma and delta variants at 3 months

  9. Neutralizing antibody titers against D614, alpha, gamma and delta variants at 12 months [ Time Frame: 12 months ]
    Neutralizing antibody titers against D614, alpha, gamma and delta variants at 12 months

  10. ELISpot IFN CD4 and CD8 response at 28 days [ Time Frame: 28 days ]
    ELISpot IFN CD4 and CD8 response at 28 days

  11. ELISpot IFN CD4 and CD8 response at 3 months [ Time Frame: 3 months ]
    ELISpot IFN CD4 and CD8 response at 3 months

  12. ELISpot IFN CD4 and CD8 response at 12 months [ Time Frame: 12 months ]
    ELISpot IFN CD4 and CD8 response at 12 months

  13. Anti-Spike (D614) and anti-RBD (D614 and B.1.351) IgG levels [ Time Frame: Day 3 ]
    Anti-Spike (D614) and anti-RBD (D614 and B.1.351) IgG levels, expressed in BAU/ml, according to WHO recommendations D3 after the booster dose mRNA or adjuvanted subunit vaccine (ancillary analysis) to assess the early humoral response by ELISA of a booster dose of mRNA vaccine or subunit adjuvanted vaccine

  14. ELISpot IFN CD4 and CD8 response [ Time Frame: 28 days, 3 months and 12 months ]
    ELISpot IFN CD4 and CD8 response (ancillary analysis); to explore CD4 and CD8 cellular response induced by a booster dose of mRNA vaccine or adjuvanted subunit vaccine (ancillary analysis)

  15. Activated (CD71+) spike Beta specific B cells will also be sorted and cultured in single cells for further analysis of their BCR and their relationship with the early CSA response. [ Time Frame: Day 3 ]

    To explore B cells (CD71) functionality

    Ancillary study endpoints:

    Cf. Coviboost ancillary study protocol.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Adult in a healthy condition or with a stable health status if pre-existing medical history. Stable health status is defined as an existing disease that has not required a significant change in treatment of hospitalization for worsening in the 3 months before enrollment, and for which neither a significant change in treatment or hospitalization for worsening is expected in the near future
  3. For women of childbearing age: a negative highly sensitive pregnancy urinary test during the inclusion visit AND use of an effective contraceptive method prior to vaccination and until at least 12 weeks after the vaccination
  4. Who has received 2 doses of mRNA vaccine (Pfizer-BioNTech) with an interval of 3 to 6 weeks
  5. Second dose of mRNA vaccine (Pfizer-BioNTech) administered 6 months +/- 1 month before the booster dose
  6. Understands and agrees to comply with the study procedures
  7. Written informed consent signed by both the participant and the investigator
  8. Subject affiliated to the French Social Security System.

Exclusion Criteria:

  1. 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, or having been in contact with an infected individual for the last 10 days before the inclusion visit;
  2. Virologically documented history of COVID-19 (PCR or serology);
  3. 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;
  4. 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;
  5. Known HIV, HCV or HBV infection;
  6. Any medical condition, such as cancer, that might impair the immune response;
  7. Use of experimental immunoglobulins, experimental monoclonal antibodies or convalescent plasma is not permitted during the study;
  8. Pregnancy or breastfeeding currently ongoing;
  9. 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;
  10. Participant who has received BCG (tuberculosis) vaccine within the previous year;
  11. Has received a vaccine within 4 weeks prior to the boost injection or is scheduled to receive a registered vaccine 4 weeks after the boost injection
  12. Any bleeding disorder considered as a contraindication to an intramuscular injection, previous phlebotomy, or receipt of anticoagulants
  13. Participation in other research involving humans (French classification Jarde 1 or Jarde 2) within 4 weeks prior to the inclusion visit, or participation in any other vaccine trial
  14. Subject under legal protection (e.g. guardianship, tutorship)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05124171


Locations
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France
GH Broca-Cochin-Hôtel-Dieu CIC 1417 Cochin-Pasteur
Paris, France, 75004
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
COVIREIVAC
Investigators
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Principal Investigator: Odile LAUNAY, PU-PH Assistance Publique - Hôpitaux de Paris
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT05124171    
Other Study ID Numbers: APHP211184
2021-004550-33 ( EudraCT Number )
First Posted: November 17, 2021    Key Record Dates
Last Update Posted: July 11, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
COVID 19
mRNA vaccines
Immunology
Sub-unit vaccine
Booster
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs