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

NCT04904549 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: VAT00008U1111-1264-3238
• Study Type: interventional
• Target: 23,670
• Locations: 11 countries
• Sites: 86

Brief Summary

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.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (21)

• Stage 1 and Stage 2: Number of Participants With 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

  From Day 36 up to Day 387

• Stage 1 and Stage 2: Number of Participants With Asymptomatic SARS-CoV-2 Infection

  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)

  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

  From first dose of study vaccine administration (Day 1) up to 387 days

Study Arms (4)

Stage 1: SARS-CoV-2 vaccine

EXPERIMENTAL

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); Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent B.1.351) (booster dose) >= 4 months after last vaccination

Stage 1: Placebo

PLACEBO COMPARATOR

2 injections of placebo at Day 1 and Day 22

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

Stage 2: SARS-CoV-2 vaccine

EXPERIMENTAL

2 injections of bivalent SARS-CoV-2 vaccine at Day 1 and Day 22

Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (bivalent D614 + B.1.351) (primary series); Biological: SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent B.1.351) (booster dose) >= 4 months after last vaccination

Stage 2: Placebo

PLACEBO COMPARATOR

2 injections of placebo at Day 1 and Day 22

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

Interventions

SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent D614) (primary series) BIOLOGICAL

Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection

Stage 1: SARS-CoV-2 vaccine

SARS-CoV-2 adjuvanted recombinant protein vaccine (bivalent D614 + B.1.351) (primary series) BIOLOGICAL

Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection.

Stage 2: SARS-CoV-2 vaccine

Placebo BIOLOGICAL

Pharmaceutical form: liquid. Route of administration: intramuscular administration.

Stage 1: Placebo; Stage 2: Placebo

SARS-CoV-2 adjuvanted recombinant protein vaccine (monovalent B.1.351) (booster dose) >= 4 months after last vaccination BIOLOGICAL

Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection.

Stage 1: SARS-CoV-2 vaccine; Stage 2: SARS-CoV-2 vaccine

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

Pharmaceutical form: emulsion for injection. Route of administration: intramuscular injection.

Stage 1: Placebo; Stage 2: Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (86)

AES - DRS - Simon Williamson Clinic, PC - Birmingham- Site Number : 8400004

Birmingham, Alabama, 35211, United States

Location

Optimal Research Alabama- Site Number : 8400019

Huntsville, Alabama, 35802, United States

Location

Peninsula Research Associates, Inc.- Site Number : 8400021

Rolling Hills Estates, California, 90274, United States

Location

Synexus Clinical Research US, Inc. Site Number : 8400013

Centennial, Colorado, 80112, United States

Location

Optimal Research, LLC-Melbourne- Site Number : 8400002

Melbourne, Florida, 32934, United States

Location

Synexus Clinical Research US, Inc. - Orlando- Site Number : 8400020

Orlando, Florida, 32806, United States

Location

AES St. Petersburg- Site Number : 8400017

Pinellas Park, Florida, 33781, United States

Location

Synexus Clinical Research US, Inc. - Atlanta- Site Number : 8400005

Atlanta, Georgia, 30328, United States

Location

Synexus Clinical Research Chicago- Site Number : 8400012

Chicago, Illinois, 60602, United States

Location

Synexus Clinical Research Evansville- Site Number : 8400008

Evansville, Indiana, 47714, United States

Location

Synexus St. Louis- Site Number : 8400006

St Louis, Missouri, 63141, United States

Location

Synexus Clinical Research US, Inc. - Henderson- Site Number : 8400018

Henderson, Nevada, 89052, United States

Location

Rochester Clinical Research, Inc.- Site Number : 8400023

Rochester, New York, 14609, United States

Location

Synexus Akron- Site Number : 8400009

Akron, Ohio, 44311, United States

Location

Synexus Clinical Research US, Inc. - Cincinnati- Site Number : 8400010

Cincinnati, Ohio, 45236, United States

Location

Synexus US Columbus- Site Number : 8400011

Columbus, Ohio, 43212, United States

Location

Synexus Clinical Research Anderson- Site Number : 8400007

Anderson, South Carolina, 29621, United States

Location

Coastal Carolina Research Center - N Charleston- Site Number : 8400022

North Charleston, South Carolina, 29405, United States

Location

American Indian Clinical Trials Research Network Site Number : 8400025

Rapid City, South Dakota, 57701, United States

Location

AES Austin- Site Number : 8400003

Austin, Texas, 78744, United States

Location

Synexus Dallas- Site Number : 8400014

Dallas, Texas, 75231, United States

Location

Synexus Clinical Research US, Inc. - San Antonio- Site Number : 8400015

San Antonio, Texas, 78229, United States

Location

AES Salt Lake City- Site Number : 8400016

Murray, Utah, 84123, United States

Location

Investigational Site Number : 1700010

Aguazul, 856018, Colombia

Location

Investigational Site Number : 1700002

Barranquilla, 080020, Colombia

Location

Investigational Site Number : 1700008

Barranquilla, 080020, Colombia

Location

Investigational Site Number : 1700001

Bogotá, 111611, Colombia

Location

Investigational Site Number : 1700005

Cali, 76001, Colombia

Location

Investigational Site Number : 1700006

Chía, 0000, Colombia

Location

Investigational Site Number : 1700004

Floridablanca, 681004, Colombia

Location

Investigational Site Number : 1700007

Girardot, 252431, Colombia

Location

Investigational Site Number : 1700009

Meta, 0000, Colombia

Location

Investigational Site Number : 1700015

Quindío, 630001, Colombia

Location

Investigational Site Number : 1700003

Soledad, 083001, Colombia

Location

Investigational Site Number : 2880002

Kintampo, P. O. Box 200, Ghana

Location

Investigational Site Number : 2880003

Kumasi, 00000, Ghana

Location

Investigational Site Number : 2880001

Navrongo, 114, Ghana

Location

Investigational Site Number : 3400001

Municipio Del Distrito Central, 11101, Honduras

Location

Investigational Site Number : 3400002

San Pedro Sula, 21104, Honduras

Location

Investigational Site Number : 3560010

Ajmer, 305001, India

Location

Investigational Site Number : 3560002

Ambawadi, 380015, India

Location

Investigational Site Number : 3560007

Belagavi, 590002, India

Location

Investigational Site Number : 3560001

Jaipur, 302039, India

Location

Investigational Site Number : 3560005

Kanpur, 208002, India

Location

Investigational Site Number : 3560009

Nagpur, 440001, India

Location

Investigational Site Number : 3560011

Odisha, 751003, India

Location

Investigational Site Number : 3560004

Patna, 801507, India

Location

Investigational Site Number : 3560003

Punjagutta, 500082, India

Location

Investigational Site Number : 3560006

Tamilnadu, 603203, India

Location

Investigational Site Number : 3920005

Chiyoda-ku,, Tokyo, 101-0041, Japan

Location

Investigational Site Number : 3920004

Haramachi,Shinjuku-ku, Tokyo, 162-0053, Japan

Location

Investigational Site Number : 3920003

Kouenji minami,Suginami-ku, Tokyo, 166-0003, Japan

Location

Investigational Site Number : 3920001

Kyobashi Chuo-ku, Tokyo, 104-0031, Japan

Location

Investigational Site Number : 3920002

Ohta-ku, Tokyo, 143-0015, Japan

Location

Investigational Site Number : 4040011

Butere, 50101, Kenya

Location

Investigational Site Number : 4040006

Eldoret, 30100, Kenya

Location

Investigational Site Number : 4040004

Kericho, 00200, Kenya

Location

Investigational Site Number : 4040002

Kisumu, 40100, Kenya

Location

Investigational Site Number : 4040003

Kisumu, 40100, Kenya

Location

Investigational Site Number : 4040012

Kisumu, 40123 Kisumu, Kenya

Location

Investigational Site Number : 4040008

Mombasa, 80107 Ganjoni, Kenya

Location

Investigational Site Number : 4040001

Nairobi, 00100GPO, Kenya

Location

Investigational Site Number : 4040007

Nairobi, 00100, Kenya

Location

Investigational Site Number : 4040009

Thika, 00202 Kiambu, Kenya

Location

Investigational Site Number : 4840005

León, Guanajuato, 37000, Mexico

Location

Investigational Site Number : 4840004

Acapulco de Juárez, Guerrero, 39670, Mexico

Location

Investigational Site Number : 4840003

Guadalajara, Jalisco, 44280, Mexico

Location

Investigational Site Number : 4840009

Mexico City, Mexico City, 04530, Mexico

Location

Investigational Site Number : 4840008

Cuernavaca, Morelos, 62290, Mexico

Location

Investigational Site Number : 4840006

Temixco, 62587, Mexico

Location

Investigational Site Number : 4840002

Veracruz, 91910, Mexico

Location

Investigational Site Number : 5240002

Dhulikhel, 45200, Nepal

Location

Investigational Site Number : 5240003

Kathmandu, 44600, Nepal

Location

Investigational Site Number : 5240001

Nepalgunj, 21900, Nepal

Location

Investigational Site Number : 8000002

Entebbe, 0, Uganda

Location

Investigational Site Number : 8000005

Entebbe, 0, Uganda

Location

Investigational Site Number : 8000001

Kampala, 0, Uganda

Location

Investigational Site Number : 8000013

Kampala, 10101, Uganda

Location

Investigational Site Number : 8000007

Kampala, 23491, Uganda

Location

Investigational Site Number : 8000003

Kampala, 42 Nakasero Road, Uganda

Location

Investigational Site Number : 8000004

Kampala, Plot 101, Lubowa, Uganda

Location

Investigational Site Number : 8000014

Lira, 10101, Uganda

Location

Investigational Site Number : 8040002

Kiev, 04210, Ukraine

Location

Investigational Site Number : 8040004

Kyiv, 01023, Ukraine

Location

Investigational Site Number : 8040003

Kyiv, 02002, Ukraine

Location

Investigational Site Number : 8040001

Kyiv, 03037, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 37716365 DERIVED

Related Links

• VAT00008 Plain Language Results Summary

MeSH Terms

Conditions

COVID-19

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

Limitations and Caveats

The study was terminated as per Sponsor decision.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi Pasteur

Contact-US@sanofi.com

800-633-1610

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: For initial, double-blind, primary series design of study: participants, outcome assessors, Investigators, laboratory personnel, and sponsor trial staff are blinded to intervention group; and those preparing the study interventions are unblinded to vaccine assignment group. For crossover / booster design of study (Stage 1 and Stage 2): unblinded
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study is designed to demonstrate clinical efficacy of each of the two SARS-CoV-2 adjuvanted recombinant protein vaccines (monovalent and bivalent). In Stage 1, the monovalent vaccine will be evaluated against a placebo control. In Stage 2, the bivalent vaccine will be assessed against a placebo control.

Study Record Dates

• First Submitted: May 26, 2021
• First Posted: May 27, 2021
• Study Start: May 26, 2021
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: June 3, 2026
• Results First Posted: June 3, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

GH (3); CO (11); KE (10); ME (7); US (23); IN (10); HO (2); NE (3); JP (5); UG (8); UA (4)