Study of Monovalent and Bivalent Recombinant Protein Vaccines Against COVID-19 in Adults 18 Years of Age and Older (VAT00008)

A Parallel-group, Phase III, Multi-stage, Modified Double-blind, Multi-armed Study to Assess the Efficacy, Safety, and Immunogenicity of Two SARS-CoV-2 Adjuvanted Recombinant Protein Vaccines (Monovalent and Bivalent) for Prevention Against COVID-19 in Adults 18 Years of Age and Older as a Primary Series and Open-label Extension to Assess Immunogenicity, Safety, Efficacy of a Monovalent Booster Dose of SARS-CoV2 Adjuvanted Recombinant Protein Vaccine

The purpose of this Phase III study is to assess the efficacy, safety, and immunogenicity of two CoV2 preS dTM-AS03 vaccines (monovalent and bivalent) as part of primary series vaccinations in a multi-stage approach, as well as a booster injection of a CoV2 preS dTM-AS03 vaccine, in adults 18 years of age and older.

A total of approximately 21 046 participants are planned to be enrolled (5080 per study intervention group in Stage 1 and 5443 per study intervention group in Stage 2).

Initial, double-blind, primary series study design is planned for 365 days post-last Initial injection (ie, approximately 386 days total) for each participant.

Based on decisions of the Study Oversight Group, Stage 1 and Stage 2 participants will be invited to participate in an unblinded Crossover / Booster study design with duration as follows:

• For participants who initially received vaccine: 12 months post-booster (ie, approximately 18 to 24 months)
• For participants who initially received placebo: ≥ 4 months post-last dose of the primary series + 12 months post-booster (ie, approximately 28 to 34 months)
• For participants who do not consent to continue in the unblinded Crossover / Booster part of the study, all study procedures will be stopped and participants will be discontinued from the study.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent D614) (primary series); Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent B.1.351) (booster dose) >= 4 months after last vaccination; Biological: Placebo; Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine(monovalent D614)(primary series)& SARS-CoV-2 adjuvanted recombinant protein vaccine(monovalent B.1.351)(booster dose)>=4 months after last vaccination; Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (bivalent D614 + B.1.351) (primary series)

Detailed Description

The duration of participation in the initial, double-blind, primary series design of the study will be approximately 365 days post-last injection (ie, approximately 386 days total) for each participant.

Based on decisions of the Study OG, Stage 1 and Stage 2 participants will be invited to participate in an unblinded Crossover / Booster study design with duration as follows:

• For participants who initially received vaccine: 12 months post-booster (ie, approximately 18 to 24 months)
• For participants who initially received placebo: ≥ 4 months post-last dose of the primary series + 12 months post-booster (ie, approximately 28 to 34 months)
• For participants who do not consent to continue in the unblinded Crossover / Booster part of the study, all study procedures will be stopped and participants will be discontinued from the study.

• Study Type: Interventional
• Enrollment (Actual): 23670
• Phase: Phase 3

Contacts and Locations

Study Locations

• Colombia
  • Aguazul, Colombia, 856018
    • Investigational Site Number : 1700010
  • Barranquilla, Colombia, 080020
    • Investigational Site Number : 1700002
  • Barranquilla, Colombia, 080020
    • Investigational Site Number : 1700008
  • Bogotá, Colombia, 111611
    • Investigational Site Number : 1700001
  • Cali, Colombia, 76001
    • Investigational Site Number : 1700005
  • Chía, Colombia, 0000
    • Investigational Site Number : 1700006
  • Floridablanca, Colombia, 681004
    • Investigational Site Number : 1700004
  • Girardot, Colombia, 252431
    • Investigational Site Number : 1700007
  • Meta, Colombia, 0000
    • Investigational Site Number : 1700009
  • Quindío, Colombia, 630001
    • Investigational Site Number : 1700015
  • Soledad, Colombia, 083001
    • Investigational Site Number : 1700003
• Ghana
  • Kintampo, Ghana, P. O. Box 200
    • Investigational Site Number : 2880002
  • Kumasi, Ghana, 00000
    • Investigational Site Number : 2880003
  • Navrongo, Ghana, 114
    • Investigational Site Number : 2880001
• Honduras
  • Municipio Del Distrito Central, Honduras, 11101
    • Investigational Site Number : 3400001
  • San Pedro Sula, Honduras, 21104
    • Investigational Site Number : 3400002
• India
  • Ajmer, India, 305001
    • Investigational Site Number : 3560010
  • Ambawadi, India, 380015
    • Investigational Site Number : 3560002
  • Belagavi, India, 590002
    • Investigational Site Number : 3560007
  • Jaipur, India, 302039
    • Investigational Site Number : 3560001
  • Kanpur, India, 208002
    • Investigational Site Number : 3560005
  • Nagpur, India, 440001
    • Investigational Site Number : 3560009
  • Odisha, India, 751003
    • Investigational Site Number : 3560011
  • Patna, India, 801507
    • Investigational Site Number : 3560004
  • Punjagutta, India, 500082
    • Investigational Site Number : 3560003
  • Tamilnadu, India, 603203
    • Investigational Site Number : 3560006
• Japan
  • Tokyo
    • Chiyoda-ku,, Tokyo, Japan, 101-0041
      • Investigational Site Number : 3920005
    • Haramachi,Shinjuku-ku, Tokyo, Japan, 162-0053
      • Investigational Site Number : 3920004
    • Kouenji minami,Suginami-ku, Tokyo, Japan, 166-0003
      • Investigational Site Number : 3920003
    • Kyobashi Chuo-ku, Tokyo, Japan, 104-0031
      • Investigational Site Number : 3920001
    • Ohta-ku, Tokyo, Japan, 143-0015
      • Investigational Site Number : 3920002
• Kenya
  • Butere, Kenya, 50101
    • Investigational Site Number : 4040011
  • Eldoret, Kenya, 30100
    • Investigational Site Number : 4040006
  • Kericho, Kenya, 00200
    • Investigational Site Number : 4040004
  • Kisumu, Kenya, 40100
    • Investigational Site Number : 4040002
  • Kisumu, Kenya, 40100
    • Investigational Site Number : 4040003
  • Kisumu, Kenya, 40123 Kisumu
    • Investigational Site Number : 4040012
  • Mombasa, Kenya, 80107 Ganjoni
    • Investigational Site Number : 4040008
  • Nairobi, Kenya, 00100GPO
    • Investigational Site Number : 4040001
  • Nairobi, Kenya, 00100
    • Investigational Site Number : 4040007
  • Thika, Kenya, 00202 Kiambu
    • Investigational Site Number : 4040009
• Mexico
  • Temixco, Mexico, 62587
    • Investigational Site Number : 4840006
  • Veracruz, Mexico, 91910
    • Investigational Site Number : 4840002
  • Guanajuato
    • León, Guanajuato, Mexico, 37000
      • Investigational Site Number : 4840005
  • Guerrero
    • Acapulco de Juárez, Guerrero, Mexico, 39670
      • Investigational Site Number : 4840004
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Investigational Site Number : 4840003
  • Mexico City
    • Mexico City, Mexico City, Mexico, 04530
      • Investigational Site Number : 4840009
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62290
      • Investigational Site Number : 4840008
• Nepal
  • Dhulikhel, Nepal, 45200
    • Investigational Site Number : 5240002
  • Kathmandu, Nepal, 44600
    • Investigational Site Number : 5240003
  • Nepalgunj, Nepal, 21900
    • Investigational Site Number : 5240001
• Uganda
  • Entebbe, Uganda
    • Investigational Site Number : 8000002
  • Entebbe, Uganda
    • Investigational Site Number : 8000005
  • Kampala, Uganda
    • Investigational Site Number : 8000001
  • Kampala, Uganda, 10101
    • Investigational Site Number : 8000013
  • Kampala, Uganda, 23491
    • Investigational Site Number : 8000007
  • Kampala, Uganda, 42 Nakasero Road
    • Investigational Site Number : 8000003
  • Kampala, Uganda, Plot 101, Lubowa
    • Investigational Site Number : 8000004
  • Lira, Uganda, 10101
    • Investigational Site Number : 8000014
• Ukraine
  • Kiev, Ukraine, 04210
    • Investigational Site Number : 8040002
  • Kyiv, Ukraine, 01023
    • Investigational Site Number : 8040004
  • Kyiv, Ukraine, 02002
    • Investigational Site Number : 8040003
  • Kyiv, Ukraine, 03037
    • Investigational Site Number : 8040001
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • AES - DRS - Simon Williamson Clinic, PC - Birmingham- Site Number : 8400004
    • Huntsville, Alabama, United States, 35802
      • Optimal Research Alabama- Site Number : 8400019
  • California
    • Rolling Hills Estates, California, United States, 90274
      • Peninsula Research Associates, Inc.- Site Number : 8400021
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Synexus Clinical Research US, Inc. Site Number : 8400013
  • Florida
    • Melbourne, Florida, United States, 32934
      • Optimal Research, LLC-Melbourne- Site Number : 8400002
    • Orlando, Florida, United States, 32806
      • Synexus Clinical Research US, Inc. - Orlando- Site Number : 8400020
    • Pinellas Park, Florida, United States, 33781
      • AES St. Petersburg- Site Number : 8400017
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Synexus Clinical Research US, Inc. - Atlanta- Site Number : 8400005
  • Illinois
    • Chicago, Illinois, United States, 60602
      • Synexus Clinical Research Chicago- Site Number : 8400012
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Synexus Clinical Research Evansville- Site Number : 8400008
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Synexus St. Louis- Site Number : 8400006
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Synexus Clinical Research US, Inc. - Henderson- Site Number : 8400018
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.- Site Number : 8400023
  • Ohio
    • Akron, Ohio, United States, 44311
      • Synexus Akron- Site Number : 8400009
    • Cincinnati, Ohio, United States, 45236
      • Synexus Clinical Research US, Inc. - Cincinnati- Site Number : 8400010
    • Columbus, Ohio, United States, 43212
      • Synexus US Columbus- Site Number : 8400011
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Synexus Clinical Research Anderson- Site Number : 8400007
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center - N Charleston- Site Number : 8400022
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • American Indian Clinical Trials Research Network Site Number : 8400025
  • Texas
    • Austin, Texas, United States, 78744
      • AES Austin- Site Number : 8400003
    • Dallas, Texas, United States, 75231
      • Synexus Dallas- Site Number : 8400014
    • San Antonio, Texas, United States, 78229
      • Synexus Clinical Research US, Inc. - San Antonio- Site Number : 8400015
  • Utah
    • Murray, Utah, United States, 84123
      • AES Salt Lake City- Site Number : 8400016

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.
• For persons living with human immunodeficiency virus (HIV), stable HIV infection determined by participant currently on antiretrovirals with CD4 count > 200/mm3.
• 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 despite encouragement by the Investigator to receive the authorized vaccine available to them at the time of enrollment.
• Informed consent form has been signed and dated
• Able to attend all visits and to comply with all study procedures
• Covered by health insurance, only if required by local, regional or national regulations

• 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 must 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 study intervention administration until at least 12 weeks after the second study intervention administration.

A participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 25 hours before any dose of study intervention.

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 study procedures based on Investigator?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.
• 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 study 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.
• Prior administration of a coronavirus vaccine (SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome).
• Receipt of solid-organ or bone marrow transplants in the past 180 days.
• Receipt of anti-cancer chemotherapy in the last 90 days.
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
• Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.
• Participation at the time of study enrollment (or in the 30 days preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage 1: SARS-CoV-2 vaccine; 2 injections of monovalent SARS-CoV-2 vaccine at Day 1 and Day 22	Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent D614) (primary series); Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection; Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent B.1.351) (booster dose) >= 4 months after last vaccination; Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection.
Placebo Comparator: Stage 1: Placebo; 2 injections of placebo at Day 1 and Day 22	Biological: Placebo; Pharmaceutical form: liquid. Route of administration: intramuscular administration.; Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine(monovalent D614)(primary series)& SARS-CoV-2 adjuvanted recombinant protein vaccine(monovalent B.1.351)(booster dose)>=4 months after last vaccination; Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection.
Experimental: Stage 2: SARS-CoV-2 vaccine; 2 injections of bivalent SARS-CoV-2 vaccine at Day 1 and Day 22	Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent B.1.351) (booster dose) >= 4 months after last vaccination; Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection.; Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (bivalent D614 + B.1.351) (primary series); Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection.
Placebo Comparator: Stage 2: Placebo; 2 injections of placebo at Day 1 and Day 22	Biological: Placebo; Pharmaceutical form: liquid. Route of administration: intramuscular administration.; Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine(monovalent D614)(primary series)& SARS-CoV-2 adjuvanted recombinant protein vaccine(monovalent B.1.351)(booster dose)>=4 months after last vaccination; Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1 and Stage 2: Number of Participants With Onset of Symptomatic Coronavirus Disease 2019 (COVID-19) Episode	Symptomatic COVID-19 was defined as virologically-confirmed SARS-CoV-2 infection accompanied by protocol-defined COVID-19-like illness (CLI).	From Day 36 up to Day 387
Stage 1 and Stage 2: Number of Participants With Solicited Injection Site and Systemic Reactions	A solicited reaction was defined as an "expected" adverse reaction (AR) (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and case report form (CRF) collected within 7 days after each injection and considered to be related to the corresponding 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 and included systemic manifestations such as headache, fever, as well as localized or topical manifestations that are not associated with the injection site.	Up to 7 days after each vaccination (post-dose on Days 1 and 22)
Stage 1 and Stage 2: Number of Participants With Unsolicited Non-Serious 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. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, that was pre-listed in the CRF in terms of diagnosis and onset window post-vaccination.	Up to 21 days after each vaccination (post-dose on Days 1 and 22)
Stage 1 and Stage 2: Number of Participants With Immediate 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. Immediate events were recorded to capture medically relevant unsolicited injection site and systemic AEs which occurred within the first 30 minutes after vaccination.	Up to 30 minutes after each vaccination (post-dose on Days 1 and 22)
Stage 1 and Stage 2: Number of Participants With Medically Attended Adverse Events (MAAE), Serious Adverse Events (SAE), and Adverse Events of Special Interest (AESI)	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.	From first dose of study vaccine administration (Day 1) up to 387 days
Stage 1 and Stage 2: Percentage of Participants With Virologically-Confirmed SARS-CoV-2 Infection and/or Symptomatic COVID-19	Virologically-confirmed SARS-CoV-2 infection was defined as a positive result for SARS CoV-2 by nucleic acid amplification test (NAAT) on at least 1 respiratory sample. This included positive results by any NAAT that included tests performed outside the trial protocol if confirmed by the adjudication committee. Symptomatic COVID-19 was defined as virologically-confirmed SARS-CoV-2 infection accompanied by protocol-defined COVID-19-like illness. Percentages are rounded off to the tenth decimal place. Here, percentage of participants with virologically-confirmed SARS-CoV-2 infection and/or symptomatic COVID-19 (regardless of adjudication) are reported.	From first dose of study vaccine administration (Day 1) up to 387 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1 and Stage 2: Number of Participants With SARS-CoV-2 Infection	SARS-CoV-2 infection was defined as a serologically-confirmed SARS-CoV-2 infection or virologically-confirmed SARS-CoV-2 infection.	From Day 36 up to Day 387
Stage 1 and Stage 2: Number of Participants With Occurrence of Severe COVID-19	Severe COVID-19 was defined as COVID-19 with any 1 of the following: 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. Admission to an intensive care unit. Death.	From Day 36 up to Day 387
Stage 1 and Stage 2: Number of Participants With Asymptomatic SARS-CoV-2 Infection	Asymptomatic SARS-CoV-2 infection was defined as SARS-CoV-2 infection, with no reported COVID-19-like illness episodes between enrollment and 14 days after the timepoint at which SARS-CoV-2 infection was ascertained.	From first dose of study vaccine administration (Day 1) up to 387 days
Stage 1 and Stage 2: Number of Swabs With Positive Nucleic Acid Amplification Test (NAAT)	The viral copies were collected as protocol-defined respiratory swabs during participant's illness episode and reported as positive continuous values. Here, duration between two consecutive positive NAAT results was calculated as: (the date of last swab tested positive) - (the date of first tested positive) + 1.	From first dose of study vaccine administration (Day 1) up to 387 days
Stage 1 and Stage 2: Number of Participants With Respective Number of Days Between Two Consecutive Positive Nucleic Acid Amplification Test	Duration between two consecutive positive NAAT results was calculated as: the date of last swab tested positive - the date of first swab tested positive + 1.	From first dose of study vaccine administration (Day 1) up to 387 days
Stage 1 and Stage 2: Number of Participants With Positive NAAT for SARS-CoV-2	Virologically-confirmed SARS-CoV-2 infection was defined as a positive result for SARS-CoV-2 by NAAT on at least 1 respiratory sample. Respiratory samples for NAAT testing were collected in participants with CLI through the study.	From first dose of study vaccine administration (Day 1) up to 387 days
Stage 1 and Stage 2: Number of Participants With Centers for Disease Control and Prevention (CDC)-Defined COVID-19	CDC-defined COVID-19 included virologically-confirmed SARS-CoV-2 infection with at least 1 of: fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, diarrhea.	From first dose of study vaccine administration (Day 1) up to 387 days
Stage 1 and Stage 2: Number of Participants With Occurrences of Hospitalized COVID-19	Hospitalized COVID-19 was defined as an episode of symptomatic COVID-19 that required inpatient hospitalization.	From first dose of study vaccine administration (Day 1) up to 387 days
Stage 1 and Stage 2: Number of Participants With Symptomatic COVID-19 With Severity of Moderate or Worse	Symptomatic COVID-19 was defined as virologically-confirmed SARS-CoV-2 infection accompanied by protocol-defined CLI. Moderate COVID-19 was defined as symptomatic COVID-19 with either shortness of breath that persisted for at least 12 hours or clinical signs of moderate illness measured at least on 2 occasions separated by 30 minutes and no clinical signs indicative of severe COVID-19.	From first dose of study vaccine administration (Day 1) up to 387 days
Stage 1 and Stage 2: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain at Days 1, 22, and 43	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 and post-vaccination on Days 22, and 43
Crossover: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G and B.1.351 Strains at Days 1, 43, 142, 163, and 322	Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 strain 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 43, 142, 163 and 322
Booster: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G and B.1.351 Strains at Days 1, 22, and 202	Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 strain 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, and 202
Stage 1 and Stage 2: Number of Responders as Determined by Neutralizing Antibody Titers Against SARS-CoV-2 D614G Strain at Days 22 and 43	Responders are participants who had baseline values below lower limit of quantification (LLOQ) with quantifiable neutralization titer above assay LLOQ at each pre-defined post-vaccination timepoint and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titers at each pre-defined post-vaccination timepoint.	Post-vaccination on Days 22 and 43
Crossover: Number of Responders as Determined by Neutralizing Antibody Titers Against SARS-CoV-2 D614G and B.1.351 Strains at Days 43, 142, 163, and 322	Responders are participants who had baseline values below LLOQ with quantifiable neutralization titer above assay LLOQ at each pre-defined post-vaccination timepoint and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titers at each pre-defined post-vaccination timepoint.	Post-vaccination on Days 43, 142, 163 and 322
Booster: Number of Responders as Determined by Neutralizing Antibody Titers Against SARS-CoV-2 D614G and B.1.351 Strains at Days 22 and 202	Responders are participants who had baseline values below LLOQ with quantifiable neutralization titer above assay LLOQ at each pre-defined post-vaccination timepoint and participants with baseline values above LLOQ with a 4-fold increase in neutralizing antibody titers at each pre-defined post-vaccination timepoint.	Post-vaccination on Days 22, and 202
Stage 1: Number of Participants With >=2-Fold and >=4-Fold Rise in Neutralizing Antibody Titers Against SARS-CoV-2 D614G Strain at Days 22 and 43	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) are reported.	Pre-vaccination on Day 1 and post-vaccination on Days 22 and 43
Crossover: Number of Participants With >=2-Fold and >=4-Fold Rise in Neutralizing Antibody Titers Against SARS-CoV-2 D614G and B.1.351 Strains at Days 43, 142, 163, and 322	Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 strain was measured with serum neutralization assay (monogram assay). Participants with neutralization antibody titers >=2-fold and >=4-fold increase from baseline (pre-vaccination) are reported.	Pre-vaccination on Day 1 and post-vaccination on Days 43, 142, 163, and 322
Booster: Number of Participants With >=2-Fold and >=4-Fold Rise in Neutralizing Antibody Titers Against SARS-CoV-2 D614G and B.1.351 Strains at Days 22 and 202	Neutralizing antibodies activity against SARS-CoV-2 D614G strain and B.1.351 strain was measured with serum neutralization assay (monogram assay). Participants with neutralization antibody titers >=2-fold and >=4-fold increase from baseline (pre-vaccination) are reported.	Pre-vaccination on Day 1 and post-vaccination on Days 22, and 202
Number of Participants With Symptomatic COVID-19 Episodes	Symptomatic COVID-19 is defined as virologically-confirmed SARS-CoV-2 infection accompanied by protocol-defined CLI. Grade 1: A type of AE that was usually transient and required only minimal treatment or therapeutic intervention and did not generally interfere with usual activities of daily living. Grade 2: A type of AE that was usually alleviated with additional therapeutic intervention and interfered with usual activities of daily living, causing discomfort but posed no significant or permanent risk of harm to the research participant. Grade 3: A type of AE that interrupted usual activities of daily living, or significantly affects clinical status, or required intensive therapeutic intervention.	Stages 1 and 2: From first dose of study vaccine administration (Day 1) up to Day 387. Crossover and Booster: From first dose of study vaccine administration (Day 1) up to Day 487
Number of Participants With COVID-19 Severity Using a 7-Point Ordinal Scale	The COVID-19 severity scale was based on the 7-point ordinal scale of clinical assessments: 1: death; 2: hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; 3: hospitalized, on non-invasive ventilation or high flow oxygen devices; 4: hospitalized, that required supplemental oxygen; 5: hospitalized, that did not require supplemental oxygen- discharged but required ongoing medical care (COVID-19 related or otherwise); 6: hospitalized, that did not require supplemental oxygen discharged without ongoing medical care; 7: not hospitalized.	Stages 1 and 2: From first dose of study vaccine administration (Day 1) up to Day 387. Crossover and Booster: From first dose of study vaccine administration (Day 1) up to Day 487
Number of Deaths Associated With 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 who 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.	Stages 1 and 2: From first dose of study vaccine administration (Day 1) up to Day 387. Crossover and Booster: From first dose of study vaccine administration (Day 1) up to Day 487

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Dayan GH, Rouphael N, Walsh SR, Chen A, Grunenberg N, Allen M, Antony J, Asante KP, Bhate AS, Beresnev T, Bonaparte MI, Celle M, Ceregido MA, Corey L, Dobrianskyi D, Fu B, Grillet MH, Keshtkar-Jahromi M, Juraska M, Kee JJ, Kibuuka H, Koutsoukos M, Masotti R, Michael NL, Neuzil KM, Reynales H, Robb ML, Villagomez Martinez SM, Sawe F, Schuerman L, Tong T, Treanor J, Wartel TA, Diazgranados CA, Chicz RM, Gurunathan S, Savarino S, Sridhar S; VAT00008 Study Team. Efficacy of a bivalent (D614 + B.1.351) SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant in adults: a phase 3, parallel, randomised, modified double-blind, placebo-controlled trial. Lancet Respir Med. 2023 Nov;11(11):975-990. doi: 10.1016/S2213-2600(23)00263-1. Epub 2023 Sep 13.

Helpful Links

• VAT00008 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2021
• Primary Completion (Actual): August 31, 2024
• Study Completion (Actual): August 31, 2024

Study Registration Dates

• First Submitted: May 26, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): May 27, 2021

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

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; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: VAT00008 (Other Identifier: Sanofi Identifier); U1111-1264-3238 (Registry Identifier: ICTRP)

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
• product manufactured in and exported from the U.S.: No