Study of Recombinant Protein Vaccines With Adjuvant as a Primary Series and as a Booster Dose Against COVID-19 in Adults 18 Years of Age and Older (VAT00002)

Immunogenicity and Safety of SARS-CoV-2 Recombinant Protein Vaccines With AS03 Adjuvant in Adults 18 Years of Age and Older as a Primary Series and Immunogenicity and Safety of a Booster Dose of SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (Two Monovalent and One Bivalent)

The primary objectives of the study are:

To assess the safety profile of the study vaccines 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 twodose priming series with the monovalent vaccine, and superior to that observed immediately before booster.

The secondary objectives of the study are:

To assess the neutralizing and binding antibody profiles after primary series vaccination at pre-defined time points during the study.

To assess the neutralizing and binding antibody responses of booster vaccination.

To describe the occurrences of laboratory-confirmed symptomatic COVID19 after primary series and booster vaccination.

To describe the occurrences of serologically-confirmed SARS-CoV-2 infection after primary series vaccination.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Biological: SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 1; Biological: SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 2; Biological: SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 3; Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (D614)-AS03, Dosage A; Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03; Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, bivalent (D614+B.1.351)-AS03; Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (D614)-AS03, Dosage B; Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 1; Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 2; Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 3; Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 4

Detailed Description

The duration of each participant's participation in the study will be approximately:

Original Phase 2 part: 365 days postinjection 2 (ie, 386 days total). Supplemental Cohorts 1 and 2: 365 days post-booster injection (ie, 366 days total).

• Study Type: Interventional
• Enrollment (Actual): 3159
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Norwood, Australia, 5067
    • Investigational Site Number : 0360003
  • Southport, Australia, 4215
    • Investigational Site Number : 0360002
  • Westmead, Australia, 2145
    • Investigational Site Number : 0360005
  • Woodville, Australia, 5011
    • Investigational Site Number : 0360004
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Investigational Site Number : 0360001
• France
  • Dijon, France, 21079
    • Investigational Site Number : 2500013
  • Limoges, France, 87042
    • Investigational Site Number : 2500008
  • Lyon, France, 69004
    • Investigational Site Number : 2500014
  • Marseille, France, 13005
    • Investigational Site Number : 2500015
  • Marseille, France, 13005
    • Investigational Site Number : 2500016
  • Nantes, France, 44093
    • Investigational Site Number : 2500006
  • Paris, France, 75679
    • Investigational Site Number : 2500005
  • Pessac, France, 33600
    • Investigational Site Number : 2500003
  • Pierre-Bénite, France, 69495
    • Investigational Site Number : 2500007
  • Rennes, France, 35033
    • Investigational Site Number : 2500004
  • Tours, France, 37044
    • Investigational Site Number : 2500002
• Honduras
  • Municipio Del Distrito Central, Honduras, 11101
    • Investigational Site Number : 3400002
  • San Pedro Sula, Honduras, 21104
    • Investigational Site Number : 3400001
• New Zealand
  • Christchurch, New Zealand, 8013
    • Investigational Site Number : 5540002
  • Nawton, New Zealand, 3243
    • Investigational Site Number : 5540007
  • Nelson, New Zealand, 7011
    • Investigational Site Number : 5540010
  • Rotorua, New Zealand, 3010
    • Investigational Site Number : 5540001
  • Auckland
    • New Lynn, Auckland, New Zealand, 0600
      • Investigational Site Number : 5540005
• Spain
  • Madrid, Spain, 28041
    • Investigational Site Number : 7240009
  • Valencia, Spain, 46020
    • Investigational Site Number : 7240008
  • Vigo, Spain, 36312
    • Investigational Site Number : 7240003
  • Galicia [Galicia]
    • Santiago de Compostela, Galicia [Galicia], Spain, 15706
      • Investigational Site Number : 7240013
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Investigational Site Number : 7240016
• United Kingdom
  • Doncaster, United Kingdom, DN4 8QN
    • Investigational Site Number : 8260014
  • Gloucester, United Kingdom, GL1 3NN
    • Investigational Site Number : 8260016
  • Harrow, United Kingdom, HA1 3UJ
    • Investigational Site Number : 8260010
  • London, United Kingdom, SW10 0LR
    • Investigational Site Number : 8260015
  • Southampton, United Kingdom, SO16 6YD
    • Investigational Site Number : 8260012
  • Halton
    • Runcorn, Halton, United Kingdom, WA7 2DA
      • Investigational Site Number : 8260011
  • Somerset
    • Bath, Somerset, United Kingdom, BA1 3NG
      • Investigational Site Number : 8260017
  • Sutton
    • Surrey, Sutton, United Kingdom, SM2 5PT
      • Investigational Site Number : 8260013
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Synexus - Clinical Research Advantage, Inc. Site Number : 8400270
  • Arizona
    • Chandler, Arizona, United States, 85225
      • Synexus Chandler Site Number : 8400251
    • Glendale, Arizona, United States, 85306
      • Synexus - Glendale. Site Number : 8400271
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Baptist Health Center for Clinical Research Site Number : 8400077
  • California
    • Los Angeles, California, United States, 90059
      • Charles R. Drew University of Medicine and Science Site Number : 8400220
    • Rolling Hills Estates, California, United States, 90274
      • Peninsula Research Associates, Inc. Site Number : 8400094
    • San Diego, California, United States, 92108
      • Optimal Research Site Number : 8400173
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University Site Number : 8400239
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • The George Washington University Site Number : 8400212
  • Florida
    • Hollywood, Florida, United States, 33024
      • Cenexel Research Centers of America Site Number : 8400089
    • Melbourne, Florida, United States, 32934
      • Optimal Research, LLC Site Number : 8400057
    • Orlando, Florida, United States, 32806
      • Synexus Clinical Research US, Inc. - Orlando Site Number : 8400179
  • Georgia
    • Decatur, Georgia, United States, 30030
      • Emory University Decatur Site Number : 8400201
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Chicago Clinical Research Institute, Inc. Site Number : 8400269
    • Peoria, Illinois, United States, 61614
      • Optimal Research Site Number : 8400187
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Synexus Clinical Research Evansville Site Number : 8400272
  • Louisiana
    • New Orleans, Louisiana, United States, 70125
      • Research Works INC Site Number : 8400045
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Optimal Research, LLC Rockville Site Number : 8400048
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital Site Number : 8400199
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Synexus St. Louis Site Number : 8400100
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Velocity Clinical Research, Omaha Site Number : 8400030
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center Site Number : 8400072
  • New York
    • Brooklyn, New York, United States, 11220
      • NYU VC-Augustana Site Number : 8400267
    • New York, New York, United States, 10016
      • New York University Langone Vaccine Center Site Number : 8400230
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center Site Number : 8400203
    • Rochester, New York, United States, 14642
      • University of Rochester Site Number : 8400207
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Site Number : 8400233
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center Site Number : 8400097
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • American Indian Clinical Trials Research Network Site Number : 8400204
  • Texas
    • Austin, Texas, United States, 78744
      • AES Austin Site Number : 8400191

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

-Aged 18 years or older on the day of inclusion. - -A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: Is of non-childbearing potential. To be considered of non-childbearing potential, a female mut be post-menopausal for at least 1 year or surgically sterile.

OR Is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to the first vaccination until at least 12 weeks after the last vaccination (ie, second dose of primary series or booster injection). A participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 4 hours before any dose of study intervention. - -Informed consent form has been signed and dated.

Able to attend all scheduled visits and to comply with all study procedures. SARS-CoV-2 rapid serodiagnostic test performed at the time of enrollment to detect presence of SARS-CoV-2 antibodies (Original Phase 2 Cohort).

For persons living with human immunodeficiency virus (HIV), stable HIV infection determined by participant currently on antiretrovirals with CD4 count > 200/mm3.

Does not intend to receive an authorized/approved COVID-19 vaccine from first vaccination to 3 weeks after the second vaccination despite encouragement by the investigator to receive the authorized vaccine available to them at the time of enrollment.

Supplemental cohorts: for participants originally enrolled in the Phase II cohort of the study, informed consent has to be signed and dated for transitioning to Supplemental Cohort 2.

Supplemental cohorts, Booster arms: 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.

Dementia or any other cognitive condition at a stage that could interfere with following the trial procedures based on Investigator or designee's judgment.

Self-reported thrombocytopenia, contraindicating intramuscular (IM) vaccination based on Investigator's judgment.

Bleeding disorder, or receipt of anticoagulants in the past 21 days preceding inclusion, contraindicating IM vaccination based on Investigator's judgment.

Unstable acute or chronic illness that in the opinion of the Investigator or designee poses additional risk as a result of participation or that could interfere with the study procedures.

Receipt of solid-organ or bone marrow transplants in the past 180 days. Receipt of anti-cancer chemotherapy in the last 90 days. Receipt of immunoglobulins, blood, or blood-derived products in the past 3 months.

Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C [≥ 100.4°F]). A prospective participant should not be included in the trial until the condition has resolved or the febrile event has subsided. 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.

Applicable to Original Phase II Cohort, Supplemental Cohort 1 and Cohort 2 Comparator Group: Prior administration of a coronavirus vaccine (SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome [MERS-CoV]). Participation at the time of study enrollment (or in the 30 days preceding the first study vaccination) or planned participation during the present study trial period in another clinical study investigating a vaccine, drug, medical device, or medical procedure. Exclusion criterion for the Supplemental Cohort 1 and Cohort 2 comparator group: positive rapid diagnostic test for SARS-CoV-2 antibodies at time of enrollment.

Exclusion criterion for participants in Supplemental Cohort 2 who were primed as participant in the Original Phase II Cohort of the present study: Receipt of authorized/conditionally approved COVID-19 vaccine after enrollment in Original Phase 2 Cohort.

Exclusion criterion for all Booster groups: Documented virologically-confirmed SARS-CoV-2 infection (by NAAT) after first dose of primary immunization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2 Cohort -SARS-CoV-2 vaccine Formulation 1; 2 injections of SARS-CoV-2 vaccine Formulation 1 at Day 1 and Day 22	Biological: SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 1; Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection; Other Names: rSP-COVID19
Experimental: Phase 2 Cohort - SARS-CoV-2 vaccine Formulation 2; 2 injections of SARS-CoV-2 vaccine Formulation 2 at Day 1 and Day 22	Biological: SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 2; Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection; Other Names: rSP-COVID19 Formulation 2
Experimental: Phase 2 Cohort - SARS-CoV-2 vaccine Formulation 3; 2 injections of SARS-CoV-2 vaccine Formulation 3 Day 1 and Day 22	Biological: SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 3; Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection; Other Names: rSP-COVID19 Formulation 3
Experimental: Supplemental Cohort 1 - Booster Monovalent (D614)-AS03 SARS-CoV-2 vaccine; Participants who were previously vaccinated 4 to < 10 months prior with an authorized mRNA or adenovirus-vector COVID-19 vaccine will receive 1 booster injection of monovalent (D614)-AS03 SARS-CoV-2 vaccine	Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (D614)-AS03, Dosage A; Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection; Other Names: rSP-COVID19 (D614)-AS03, Dosage A
Experimental: Supplemental Cohort 2 - Booster Monovalent (B.1.351)-AS03 SARS-CoV-2 vaccine; Participants who were vaccinated 4 to < 10 months prior with an authorized mRNA or adenovirus-vector COVID-19 vaccine or SARS-Cov-2 vaccine will receive 1 booster injection of monovalent (B.1.351)-AS03 SARS-CoV-2 vaccine	Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03; Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection; Other Names: rSP-COVID19 (B.1.351)-AS03
Experimental: Supplemental Cohort 2 - Booster Bivalent (D614 + B.1.351)-AS03 SARS-CoV-2 vaccine; Participants who were vaccinated 4 to < 10 months prior with an authorized mRNA or adenovirus-vector COVID-19 vaccine will receive 1 booster injection of bivalent (D614+B.1.351)-AS03 SARS-CoV-2 vaccine	Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, bivalent (D614+B.1.351)-AS03; Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection; Other Names: rSP-COVID19 (D614+B.1.351)-AS03
Experimental: Supplemental Cohort 2 - Booster Monovalent (D614)-AS03 SARS-CoV-2 vaccine; Participants who were vaccinated 4 to < 10 months prior with SARS-Cov-2 vaccine will receive 1 booster injection of monovalent (D614)-AS03 SARS-CoV-2 vaccine	Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (D614)-AS03, Dosage A; Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection; Other Names: rSP-COVID19 (D614)-AS03, Dosage A
Active Comparator: Supplemental Comparator for Cohort 1 and 2 Boosters - Monovalent (D614)-AS03 SARS-CoV-2 vaccine; 2 injections of monovalent (D614)-AS03 SARS-CoV-2 vaccine at Day 1 and Day 22 in previously unvaccinated, naïve participants	Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (D614)-AS03, Dosage B; Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection; Other Names: rSP-COVID19 (D614)-AS03, Dosage B
Experimental: Cohort 2 - Booster Exploratory 1; Participants who were vaccinated 4 to < 10 months prior with an authorized mRNA COVID-19 vaccine will receive 1 booster injection of monovalent (B.1.351)-AS03 SARS-CoV-2 vaccine	Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 1; Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection; Other Names: rSP-COVID19 (B.1.351)-AS03 Alternative Exploratory Formulation 1
Experimental: Cohort 2 - Booster Exploratory 2; Participants who were vaccinated 4 to < 10 months prior with an authorized mRNA COVID-19 vaccine will receive 1 booster injection of monovalent (B.1.351)-AS03 SARS-CoV-2 vaccine	Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 2; Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection; Other Names: rSP-COVID19 (B.1.351)-AS03 Alternative Exploratory Formulation 2
Experimental: Cohort 2 - Booster Exploratory 3; Participants who were vaccinated 4 to < 10 months prior with an authorized mRNA COVID-19 vaccine will receive 1 booster injection of monovalent (B.1.351)-AS03 SARS-CoV-2 vaccine	Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 3; Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection; Other Names: rSP-COVID19 (B.1.351)-AS03 Alternative Exploratory Formulation 3
Experimental: Cohort 2 - Booster Exploratory 4; Participants who were vaccinated 4 to < 10 months prior with an authorized mRNA COVID-19 vaccine will receive 1 booster injection of monovalent (B.1.351)-AS03 SARS-CoV-2 vaccine	Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 4; Pharmaceutical form: Emulsion for injection Route of administration: Intramuscular injection; Other Names: rSP-COVID19 (B.1.351)-AS03 Alternative Exploratory Formulation 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Number of Participants With Immediate Unsolicited Adverse Events (AEs)	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Immediate events were recorded to capture medically relevant unsolicited systemic AEs which occurred within the first 30 minutes after vaccination. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, that is, pre-listed in the case report form (CRF) in terms of diagnosis and onset window post-vaccination.	Up to 30 minutes after each vaccination (Phase 2: Postdose on Days 1 and 22; Phase 3: Between 4 to 10 months after priming vaccine)
Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Number of Participants With Solicited Injection Site Reactions and Systemic Reactions	A solicited reaction was an "expected" adverse reaction (AR) (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF, and were considered to be related to the study vaccine administered. An injection site reaction was an AR at and around the injection site of the study vaccine. Systemic AR were all ARs that were not injection site reactions.	Up to 7 days after each vaccination (Phase 2: Postdose on Days 1 and 22; Phase 3: Between 4 to 10 months after priming vaccine)
Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Number of Participants With Unsolicited Adverse Events	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, that is, pre-listed in the CRF in terms of diagnosis and onset window post-vaccination.	Up to 21 days after each vaccination (Phase 2: Postdose on Days 1 and 22; Phase 3: Between 4 to 10 months after priming vaccine)
Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Number of Participants With Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and Medically Attended Adverse Events (MAAEs)	An SAE was defined as any AE that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An AESI (serious or non-serious) was 1 of scientific and medical concern specific to the Sponsor's study intervention or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor could be appropriate. An MAAE was a new onset or a worsening of a condition that prompted the participant or participant's parent/guardian to seek unplanned medical advice at a physician's office or Emergency Department.	Phase 2 and Phase 3 Comparator: From first dose of study vaccine administration (Day 1) up to 387 days. Phase 3 Cohorts 1 and 2: From first dose of study vaccine administration (Day 1) up to 366 days.
Phase 2: Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) D614G Strain at Day 1	Neutralizing antibodies activity against SARS-CoV-2 D614G strain was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.	Pre-vaccination on Day 1
Phase 2: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain at Day 36	Neutralizing antibodies activity against SARS-CoV-2 D614G strain was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.	Day 36
Phase 2: Number of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titers Against SARS-CoV-2 D614G Strain at Day 36	Neutralizing antibodies activity against SARS-CoV-2 D614G strain was measured with serum neutralization assay (monogram assay). Participants with neutralization antibody titers >=2-fold and >=4-fold increase from baseline (pre-vaccination) were analyzed.	Day 1 (pre-vaccination) and Day 36
Phase 2: Number of Responders as Determined by Neutralizing Antibody Titers Against SARS-CoV-2 D614G Strain at Day 36	Responders were participants who had baseline values below lower limit of quantification (LLOQ) with detectable neutralization titer above assay LLOQ at each pre-defined post-vaccination time point and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titers at each pre-defined post-vaccination time point.	Day 36
Phase 3: Cohorts 1 and 2: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Day 1	Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 variant was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.	Pre-vaccination on Day 1
Phase 3: Cohorts 1, 2 and Comparator: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain and B.1.351 Variant at 14 Days Post-Vaccination	Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 variant was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.	Cohorts 1 and 2: 14 days post-vaccination on Day 1, Day 15; Comparator: 14 days post-vaccination on Day 22, Day 36
Phase 3: Comparator: Percentage of Responders as Determined by Neutralizing Antibody Titers Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Day 36	Responders were participants who had baseline values below LLOQ with detectable neutralization titer above assay LLOQ at each pre-defined post-vaccination time point and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titers at each pre-defined post-vaccination time point. Percentages are rounded off to the tenth decimal place.	Day 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain at Days 22, 78, 134, 202, 292, and 387	Neutralizing antibodies activity against SARS-CoV-2 D614G strain was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.	Post-vaccination on Days 22, 78, 134, 202, 292, and 387
Phase 2: Number of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titers Against SARS-CoV-2 D614G Strain at Days 22, 78, 134, 202, 292, and 387	Neutralizing antibodies activity against SARS-CoV-2 D614G strain was measured with serum neutralization assay (monogram assay). Participants with neutralization antibody titers >=2-fold and >=4-fold increase from baseline (pre-vaccination) were analyzed.	Pre-vaccination on Day 1 and Post-vaccination on Days 22, 78, 134, 202, 292, and 387
Phase 2: Number of Responders as Determined by Neutralizing Antibody Titers Against SARS-CoV-2 D614G Strain at Days 22, 78, 134, 202, 292, and 387	Responders were participants who had baseline values below LLOQ with detectable neutralization titer above assay LLOQ at each pre-defined post-vaccination time point and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titers at each pre-defined post-vaccination time point. Neutralizing antibodies activity against SARS-CoV-2 D614G strain was measured with serum neutralization assay (monogram assay).	Post-vaccination on Days 22, 78, 134, 202, 292, and 387
Phase 2: Geometric Mean Concentration (GMC) of Binding Antibodies Against SARS-CoV-2 D614G Strain at Days 1, 22, 36, 78, 134, 202, 292, and 387	Binding antibodies activity against SARS-CoV-2 D614G strain was measured with Nexelis GCN4 S-enzyme-linked immunosorbent assay (ELISA) and the results were expressed as geometric mean titers.	Pre-vaccination on Day 1 and post-vaccination on Days 22, 36, 78, 134, 202, 292, and 387
Phase 2: Number of Participants With >=2-Fold and >=4-Fold Rise in Binding Antibody Concentration Against SARS-CoV-2 D614G Strain at Days 22, 36, 78, 134, 202, 292, and 387	Binding antibodies concentration against SARS-CoV-2 D614G strain was measured with Nexelis GCN4 S-ELISA assay. Participants with binding antibodies concentration >=2-fold and >=4-fold increase from baseline (pre-vaccination) were analyzed.	Pre-vaccination on Day 1 and Post-vaccination on Days 22, 36, 78, 134, 202, 292, and 387
Phase 2: Number of Responders as Determined by Binding Antibody Concentration Against SARS-CoV-2 D614G Strain at Days 22, 36, 78, 134, 202, 292, and 387	Responders were participants who had baseline values below LLOQ with detectable antibody concentration above assay LLOQ at each pre-defined post-vaccination time point and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titers at each pre-defined post-vaccination time point. Binding antibodies concentration against SARS-CoV-2 D614G strain was measured with Nexelis GCN4 S-ELISA assay.	Post-vaccination on Days 22, 36, 78, 134, 202, 292, and 387
Phase 3: Cohort 1: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Days 29, 91, 181, and 366	Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 variant was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.	Post-vaccination on Days 29, 91, 181, and 366
Phase 3: Cohort 1: Number of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titers Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Days 15, 29, 91, 181, and 366	Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 variant was measured with serum neutralization assay (monogram assay). Participants with neutralization antibody titers >=2-fold and >=4-fold increase from baseline (pre-vaccination) were analyzed.	Pre-vaccination on Day 1 and Post-vaccination on Days 15, 29, 91, 181, and 366
Phase 3: Cohorts 1, 2 and Comparator: Percentage of Participants With Seroresponse Against SARS-CoV-2 D614G Strain and B.1.351 Variant at 14 Days Post-Vaccination	Seroresponse was defined as a >=4-fold rise in serum neutralization titer against SARS-CoV-2 D614G strain and B.1.351 variant (post/pre) at Day 15 or Day 36 relative to Day 0 or Day 22. Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 variant was measured with serum neutralization assay (monogram assay). Percentages are rounded off to the tenth decimal place.	Cohorts 1 and 2: 14 days post-vaccination on Day 1 (Day 15); Comparator: 14 days post-vaccination on Day 22 (Day 36)
Phase 3: Cohorts 1 and 2: Geometric Mean Concentration of Binding Antibodies Against SARS-CoV-2 D614G Strain at Days 1, 15, 29, 91, 181, and 366	Binding antibodies activity against SARS-CoV-2 D614G strain was measured with Nexelis GCN4 S-ELISA and the results were expressed as geometric mean titers.	Pre-vaccination on Day 1 and post-vaccination on Days 15, 29, 91, 181, and 366
Phase 3: Cohorts 1 and 2: Number of Participants With >=2-Fold and >=4-Fold Rise in Binding Antibody Concentration Against SARS-CoV-2 D614G Strain at Days 15, 29, 91, 181, and 366	Binding antibodies concentration against SARS-CoV-2 D614G strain was measured with Nexelis GCN4 S-ELISA assay. Participants with binding antibodies concentration >=2-fold and >=4-fold increase from baseline (pre-vaccination) were analyzed.	Pre-vaccination on Day 1 and Post-vaccination on Days 15, 29, 91, 181, and 366
Phase 3: Cohort 2: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Days 1, 15, 29, and 91	Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 variant was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.	Pre-vaccination on Day 1 and post-vaccination on Days 15, 29, and 91
Phase 3: Cohort 2: Number of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titers Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Days 15, 29, and 91	Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 variant was measured with serum neutralization assay (monogram assay). Participants with neutralization antibody titers >=2-fold and >=4-fold increase from baseline (pre-vaccination) were analyzed.	Pre-vaccination on Day 1 and Post-vaccination on Days 15, 29, and 91
Phase 3: Comparator: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Days 1, 22, 36, 134, 202, 292, and 387	Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 variant was measured with the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.	Pre-vaccination on Day 1 and post-vaccination on Days 22, 36, 134, 202, 292, and 387
Phase 3: Comparator: Number of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titers Against SARS-CoV-2 D614G Strain and B.1.351 Variant at Days 22, 36, 134, 202, 292, and 387	Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 variant was measured with serum neutralization assay (monogram assay). Participants with neutralization antibody titers >=2-fold and >=4-fold increase from baseline (pre-vaccination) were analyzed.	Pre-vaccination on Day 1 and Post-vaccination on Days 22, 36, 134, 202, 292, and 387
Phase 3: Comparator: Geometric Mean Concentration of Binding Antibodies Against SARS-CoV-2 D614G Strain at Days 1, 22, 36, 134, 202, 292, and 387	Binding antibodies activity against SARS-CoV-2 D614G strain was measured with Nexelis GCN4 S-ELISA and the results were expressed as geometric mean titers.	Pre-vaccination on Day 1 and post-vaccination on Days 22, 36, 134, 202, 292, and 387
Phase 3: Comparator: Number of Participants With >=2-Fold and >=4-Fold Rise in Binding Antibody Concentration Against SARS-CoV-2 D614G Strain at Days 22, 36, 134, 202, 292, and 387	Binding antibodies concentration against SARS-CoV-2 D614G strain was measured with Nexelis GCN4 S-ELISA assay. Participants with binding antibodies concentration >=2-fold and >=4-fold increase from baseline (pre-vaccination) were analyzed.	Pre-vaccination on Day 1 and Post-vaccination on Days 22, 36, 134, 202, 292, and 387
Phase 3: Comparator: Percentage of Responders as Determined by Binding Antibody Concentration Against SARS-CoV-2 D614G Strain at Days 22, 36, 134, 202, 292, and 387	Responders were participants who had baseline values below LLOQ with detectable antibody concentration above assay LLOQ at each pre-defined post-vaccination time point and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titers at each pre-defined post-vaccination time point. Binding antibodies activity against SARS-CoV-2 D614G strain was measured with Nexelis GCN4 S-ELISA. Percentages are rounded off to the tenth decimal place.	Post-vaccination on Days 22, 36, 134, 202, 292, and 387
Phase 2: Percentage of Participants With Serologically-Confirmed SARS-CoV-2 Infection	Blood samples collected from participants were used for serological assessments in the study. Serologically-confirmed SARS-CoV-2 infection was defined as a positive result in a serum sample for antibodies specific to the nucleocapsid of SARS-CoV-2 detected by electrochemiluminescence immunoassay. Percentages are rounded off to the tenth decimal place.	From first dose of study vaccine administration (Day 1) up to 387 days
Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Percentage of Participants With Laboratory-Confirmed Symptomatic COVID-19	Laboratory-confirmed SARS-CoV-2 infection was defined as a positive result for SARS-CoV-2 by nucleic acid amplification test (done by the central laboratory or locally) on at least 1 respiratory sample. Percentages are rounded off to the tenth decimal place.	Phase 2 and Phase 3 Comparator: From first dose of study vaccine administration (Day 1) up to 387 days. Phase 3 Cohorts 1 and 2: From first dose of study vaccine administration (Day 1) up to 366 days.
Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Percentage of Participants With Symptomatic COVID-19 Episodes Associated With Hospitalization	Symptomatic COVID-19 was defined as laboratory-confirmed SARS-CoV-2 infection accompanied by protocol-defined COVID-19-like illness. Percentages are rounded off to the tenth decimal place.	Phase 2 and Phase 3 Comparator: From first dose of study vaccine administration (Day 1) up to 387 days. Phase 3 Cohorts 1 and 2: From first dose of study vaccine administration (Day 1) up to 366 days.
Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Percentage of Participants With Severe Symptomatic COVID-19	Severe COVID-19 was defined as COVID-19 with any 1: Any clinical signs of severe illness measured at least on 2 occasions separated by 30 minutes, supplemental oxygen administration for >1 hour, use of invasive or non-invasive ventilation or Extracorporeal Membrane Oxygenation, clinical diagnosis of respiratory failure, significant acute renal, hepatic, or neurologic dysfunction, shock (defined by systolic blood pressure ˂90 millimeter of mercury (mmHg), or diastolic blood pressure ˂60 mmHg or requiring vasopressors), admission to an intensive care unit, or death. Symptomatic COVID-19 was defined as laboratory-confirmed SARS-CoV-2 infection accompanied by protocol-defined COVID-19-like illness. Percentages are rounded off to the tenth decimal place.	Phase 2 and Phase 3 Comparator: From first dose of study vaccine administration (Day 1) up to 387 days. Phase 3 Cohorts 1 and 2: From first dose of study vaccine administration (Day 1) up to 366 days.
Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Percentage of Participants With Death Associated With Symptomatic COVID-19	Death associated with COVID-19 was defined as death in a participant with COVID-19 who died within 28 days of the first positive specimen date OR died more than 28 days after the first specimen date and COVID-19 was mentioned as an immediate or underlying cause of death on the death certificate. Symptomatic COVID-19 was defined as laboratory-confirmed SARS-CoV-2 infection accompanied by protocol-defined COVID-19-like illness. Percentages are rounded off to the tenth decimal place.	Phase 2 and Phase 3 Comparator: From first dose of study vaccine administration (Day 1) up to 387 days. Phase 3 Cohorts 1 and 2: From first dose of study vaccine administration (Day 1) up to 366 days.

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company
• Collaborators: GlaxoSmithKline
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

General Publications

• Sridhar S, Joaquin A, Bonaparte MI, Bueso A, Chabanon AL, Chen A, Chicz RM, Diemert D, Essink BJ, Fu B, Grunenberg NA, Janosczyk H, Keefer MC, Rivera M DM, Meng Y, Michael NL, Munsiff SS, Ogbuagu O, Raabe VN, Severance R, Rivas E, Romanyak N, Rouphael NG, Schuerman L, Sher LD, Walsh SR, White J, von Barbier D, de Bruyn G, Canter R, Grillet MH, Keshtkar-Jahromi M, Koutsoukos M, Lopez D, Masotti R, Mendoza S, Moreau C, Ceregido MA, Ramirez S, Said A, Tavares-Da-Silva F, Shi J, Tong T, Treanor J, Diazgranados CA, Savarino S. Safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein vaccine (CoV2 preS dTM) in healthy adults: interim findings from a phase 2, randomised, dose-finding, multicentre study. Lancet Infect Dis. 2022 May;22(5):636-648. doi: 10.1016/S1473-3099(21)00764-7. Epub 2022 Jan 25.
• de Bruyn G, Wang J, Purvis A, Ruiz MS, Adhikarla H, Alvi S, Bonaparte MI, Brune D, Bueso A, Canter RM, Ceregido MA, Deshmukh S, Diemert D, Finn A, Forrat R, Fu B, Gallais J, Griffin P, Grillet MH, Haney O, Henderson JA, Koutsoukos M, Launay O, Torres FM, Masotti R, Michael NL, Park J, Rivera-Medina DM, Romanyak N, Rook C, Schuerman L, Sher LD, Tavares-Da-Silva F, Whittington A, Chicz RM, Gurunathan S, Savarino S, Sridhar S; VAT00002 booster cohorts study team. Safety and immunogenicity of a variant-adapted SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant as a booster in adults primed with authorized vaccines: a phase 3, parallel-group study. EClinicalMedicine. 2023 Jul 22;62:102109. doi: 10.1016/j.eclinm.2023.102109. eCollection 2023 Aug.

Helpful Links

• VAT00002 Plain language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Actual): June 29, 2023
• Study Completion (Actual): June 29, 2023

Study Registration Dates

• First Submitted: February 18, 2021
• First Submitted That Met QC Criteria: February 18, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Immunologic Factors; Physiological Effects of Drugs; Vaccines
• Other Study ID Numbers: VAT00002; U1111-1251-4616 (Registry Identifier: ICTRP); 2020-003370-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No