Study of adjuvanted recombinant COVID-19 vaccine candidate as a Primary Series and as a Booster Dose Against COVID-19

The Sanofi and GSK adjuvanted recombinant COVID-19 vaccine candidate has been evaluated in a phase 2, randomized, modified double-blind, multi center, dose-finding study (VAT00002)1, conducted in adults 18 years of age and older to evaluate its safety, reactogenicity, and immunogenicity.

During the first stage of the study, 3 different antigen doses (effective doses of 5 µg, 10 µg, and 15 µg of CoV2 preS dTM monovalent D614 antigen) with a full dose of AS03 adjuvant were evaluated as a primary vaccination series of 2 injections administered 21 days apart.

As previously reported in interim results2, the candidate achieved strong rates of neutralizing antibody responses with 95% to 100% seroconversion following the second injection in all age groups (18 to 95 years old) and across all doses, with acceptable tolerability and with no safety concerns. Overall, the vaccine candidate elicited neutralizing antibody levels that were comparable to those generated by natural infection, with higher levels observed in younger adults (18 to 59 years old). Based on these Phase 2 interim results, the companies initiated a global Phase III study (VAT00008)3,4.

Meanwhile, with the decline of the original wildtype strain SARS-CoV-2 and the rise of new variants of concern, as well as the waning immunity in vaccinated and previously infected individuals against contracting COVID-19, it is expected that many people will need to receive booster vaccinations in the next 12 months.

To address the emergence of variant strains of concern, Sanofi Pasteur is developing monovalent and bivalent vaccine formulations containing prototype D614 (original Wuhan virus) and/or the Beta (B.1.351) variant first identified in South Africa, which will be studied in three additional study cohorts1. In this phase 2/3, parallel, multi-center study, Sanofi Pasteur will assess the use of the vaccine candidates as boosters amongst people who have been previously vaccinated with mRNA, recombinant protein and/or viral vector technology vaccines, with the aim to provide extended protection against variants described for having decreased vaccine efficacy with the first COVID-19 vaccines generation containing the initial strain5.

For more information on the phase 2 booster clinical trial per country,
please refer to the following contact list:

USA
Call center number: 1-800-633-1610
Sanofi Trial Transparency mailbox: Contact-US@sanofi.com   

Australia
Call center number : 1800 818 806
Medical Information mailbox: MedInfo.Australia@sanofi.com

   

Our phase 2 booster study (NCT04762680)

In the original phase 2 cohort:  
Participants received 2 injections 21 days apart of one of the 3 different doses of CoV2 preS dTM antigen with fixed dose of AS03 adjuvant.

In the supplemental booster and variant-priming cohorts:
>4500 participants
Volunteers in previously vaccinated groups will receive either a single booster dose of Monovalent (D614) AS03 vaccine or Bivalent (D614 + B.1.351)-AS03 or a single dose of Monovalent (B.1.351) with or without AS03 adjuvant. No placebo control will be given in this study. 
An additional cohort of SARS-CoV-2-naïve, unvaccinated adults who are 18-55 years of age, will receive 2 doses of Monovalent (D614)-AS03 or Monovalent (B.1.351)-AS03 or Bivalent (D614 + B.1.351)-AS03 vaccine candidate as a primary vaccination series.  

Primary objectives and endpoints

  • To assess the safety profile of the vaccine candidate among all participants in each age group and in each study intervention group.
  • To assess the neutralizing antibody profile after primary series vaccination in SARS-CoV-2-naïve adults.
  • To demonstrate that a booster dose of monovalent or bivalent SARS-CoV-2 vaccine given to adults previously vaccinated with an authorized/approved COVID-19 vaccine induces an immune response that is non-inferior to the response induced by a two-dose priming series with the monovalent vaccine, and superior to that observed immediately before booster.
  • To demonstrate that two doses of monovalent (B.1.351)-AS03 or bivalent (D614 + B.1.351)-AS03 SARS-CoV-2 vaccine induce an immune response that is non inferior to the response induced by monovalent (D614)-AS03 vaccine. 

Eligibility criteria

For Original Phase 2 Cohort, the number of participants who were positive for SARS-Cov-2 (as shown by rapid serodiagnostic test upon enrollment) were capped at approximately 20% of the study population to ensure there is a sufficient number of SARS-CoV-2 naïve participants in the study.
Participants with medical conditions that put them at high risk for COVID-19 will also be included. 

Aged 18 years old or older
Able to attend all scheduled visits and to comply with all study procedures
Does not intend to receive an authorized/approved COVID-19 vaccine from inclusion to the study to 3 weeks after the vaccination

Inclusion criteria

  • Aged 18 years or older 
  • Women are eligible if not pregnant nor breastfeeding
  • Able to attend all scheduled visits and to comply with all study procedures
  • Original cohort: Willingness to have a SARS-CoV-2 rapid serodiagnostic test performed at the time of enrollment to detect presence of SARS-CoV-2 antibodies.   
  • Does not intend to receive an authorized/approved COVID-19 vaccine from the time of first vaccination in this study to 3 weeks after the second vaccination, despite encouragement by the investigator to receive available authorized vaccine(s).
  • Booster arms: Participants who have received a complete primary vaccination series with an authorized/conditionally approved mRNA COVID-19 vaccine (mRNA-1273 [Moderna] or BNT162b2 [Pfizer/BioNTech]) or adenovirus-vectored COVID-19 vaccine (ChAdOx1 nCoV-19 [Oxford University/AstraZeneca] or Ad26.CoV2.S [J&J/Janssen]), with the last dose administered a minimum of 4 months prior to inclusion but not longer than 10 months prior to inclusion.  

Exclusion criteria 

  • Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to a vaccine containing any of the same substances
  • Receipt of any vaccine in the 30 days preceding or on the day of the first study vaccination or planned receipt of any vaccine between the first study vaccination and in the 30 days following the second study vaccination. 
    • Except for influenza vaccination which may be received at any time in relation to study intervention.
  • Original Phase II Cohort and Supplemental priming cohorts: Prior administration of a coronavirus vaccine (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], SARS-CoV, Middle East Respiratory Syndrome [MERS-CoV])

How does the Trial Work?

References

  1. Study of Recombinant Protein Vaccines With Adjuvant as a Primary Series and as a Booster Dose against COVID-19 in Adults 10 Years of Age and Older. Available at: https://clinicaltrials.gov/ct2/show/NCT04762680  
  2. Sanofi and GSK COVID-19 vaccine candidate demonstrates strong immune responses across all adult age groups in Phase 2 trial, Press release, 17 May 202. Available at: https://www.sanofi.com/en/media-room/press-releases/2021/2021-05-17-07-30-00-2230312
  3. Study of Monovalent and Bivalent Recombinant Protein Vaccines Against COVID-19 in Adults 18 Years of Age and Older (VAT00008). Available at: https://clinicaltrials.gov/ct2/show/NCT04904549
  4. Sanofi and GSK initiate global Phase 3 clinical efficacy study of COVID-19 vaccine candidate. https://www.sanofi.com/en/media-room/press-releases/2021/2021-05-27-07-30-00-2236989
  5. Overview of data to inform recommendations for booster doses of COVID-19 vaccines/ CDC. Sara Oliver, June 23, 2021. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-06/06-COVID-Oliver-508.pdf