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

NCT05405283 | Unknown Phase 3 DMC

• 2 other identifiers: AP2111842021-004550-33
• Study Type: interventional
• Target: 189
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

COVID-19 Vaccines

Keywords

COVID 19; mRNA vaccines; Immunology; Sub-unit vaccine; Second booster

Outcome Measures

Primary Outcomes (1)

• Immunogenicity of a second booster 15 days after receiving the second booster

  Proportion of patient with an increase of at least 10-fold between D0 and D15 after the 2nd booster dose in neutralizing antibody titers against SARS-CoV-2 D614,B.1.351, Delta and Omicron BA.1 and BA.2 viral strains, measured by a microneutralization technique. A 10-fold increase implies that the second titer is at least 2 dilutions higher than the first, which represents an unambiguous increase according to the state of the art of serum neutralization.

  15 days after second booster

Secondary Outcomes (7)

• Rate of neutralizing antibody titer against SARS-CoV-2 viral at 6 and 12 months

  Up to 12 months after second booster

• Number and intensity of local and systemic adverse events at 28 days

  Up to 28 days after second booster

• Anti-Spike and anti-RBD IgG levels at 6 and 12 months

  Up to 12 months after second booster

• Difference in anti-Spike and anti-RBD B.1.351 IgG level at 6 months and 12 months

  6 months

• Difference in anti-Spike and anti-RBD B.1.351 IgG level at D15

  15 days

Study Arms (2)

Comirnaty® (Pfizer-BioNTech)

ACTIVE COMPARATOR

Biological: 2nd booster with Comirnaty® (Pfizer-BioNTech)

CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK

EXPERIMENTAL

Biological: CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK

Interventions

2nd booster with Comirnaty® (Pfizer-BioNTech) BIOLOGICAL

In participants previously vaccinated with 3 doses of mRNA vaccine, he/she will receive one dose of Comirnaty® (Pfizer-BioNTech) vaccine as a second booster

Comirnaty® (Pfizer-BioNTech)

CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK BIOLOGICAL

In participants previously vaccinated with 3 doses of mRNA vaccine, he/she will receive one dose of CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK vaccine as a second booster

CoV2 preS dTM adjuvanted vaccine (B.1.351), Sanofi/GSK

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 60 years.
• For participants over 60 years of age who participated in Coviboost, to have received a booster dose of mRNA vaccine (Pfizer-BioNTech) administered at least 6 months before the 2nd booster dose
• Not included in Coviboost (new participants to be recruited) and having received 2 doses of mRNA vaccine (Pfizer-BioNTech) with an interval of 3 to 6 weeks and a 1st booster dose of mRNA vaccine (Pfizer-BioNTech) or Moderna administered at least 6 months before the 2nd booster dose
• Understands and agrees to comply with the study procedures.
• Written informed consent signed by the participant and the investigator.
• Person affiliated to a social security scheme.

You may not qualify if:

• Virologically documented (PCR or serology) history of COVID 19.
• Known HIV, HCV or HBV infection.
• Any condition, such as cancer, that may reduce the immune response.
• Use of experimental Ig, experimental monoclonal antibodies or convalescent serum is not allowed during the study.
• History of severe adverse reactions after vaccine administration including anaphylactic reaction and associated symptoms such as rash, difficulty breathing, angioedema and abdominal pain, or a history of an allergic reaction that may be exacerbated by a component of the SARS-COV-2 vaccine during the first vaccine injection.
• Participant having been vaccinated against BCG in the previous year.
• Having received a vaccination within 2 weeks prior to the 2nd booster dose or scheduled to receive a licensed vaccine 2 weeks after the 2nd booster dose.
• Any bleeding disorder considered as a contraindication to an intramuscular injection, previous phlebotomy or receipt of anticoagulants.
• Subject under legal protection (e.g. guardianship, tutorship).

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• IREIVAC/COVIREIVAC Network: collaborator

Study Sites (1)

GH Broca-Cochin-Hôtel-Dieu CIC 1417 Cochin-Pasteur

Paris, 75004, France

Location

MeSH Terms

Conditions

COVID-19

Interventions

BNT162 Vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors

Study Officials

• Odile Launay

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2022
• First Posted: June 6, 2022
• Study Start: June 8, 2022
• Primary Completion: July 15, 2022
• Study Completion: July 1, 2023
• Last Updated: July 3, 2023

Record last verified: 2023-06

Locations

FR (1)