NCT04537208

Brief Summary

The primary objectives of the study were:

  • To describe the neutralizing antibody profile at Day 1, Day 22, and Day 36 of each study intervention group.
  • To describe the safety profile of all participants in each age group and each study intervention group up to 12 months post-last injection. The secondary objectives of the study are:
  • To describe binding antibody profile at Day 1, Day 22, Day 36, Day 181 (Cohort 1) or Day 202 (Cohort 2), and Day 366 (Cohort 1) or Day 387 (Cohort 2) of each study intervention group.
  • To describe the neutralizing antibody profile at Day 181 (Cohort 1) or Day 202 (Cohort 2) and at Day 366 (Cohort 1) and Day 387 (Cohort 2) of each study intervention group.
  • To describe the occurrence of virologically-confirmed coronavirus disease (COVID-19)-like illness and serologically-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
  • To evaluate the correlation / association between antibody responses to SARS-CoV-2 Recombinant Protein and the risk of virologically-confirmed COVID-19-like illness and/or serologically-confirmed SARS-CoV-2 infection.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
441

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Sep 2020

Geographic Reach
1 country

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 2, 2020

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 3, 2020

Completed
Same day until next milestone

Study Start

First participant enrolled

September 3, 2020

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 19, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 19, 2021

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

June 22, 2023

Completed
Last Updated

September 17, 2025

Status Verified

May 1, 2023

Enrollment Period

1.2 years

First QC Date

September 2, 2020

Results QC Date

May 24, 2023

Last Update Submit

September 15, 2025

Conditions

COVID-19 (Healthy Volunteers)

Outcome Measures

Primary Outcomes (17)

  • Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 1

    GMTs of SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. Titers were expressed in terms of 1/dilution.

    Day 1 (pre-vaccination)

  • Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 22

    GMTs of SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. Titers were expressed in terms of 1/dilution.

    Day 22 (post-vaccination)

  • Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 36

    GMTs of SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. Titers were expressed in terms of 1/dilution.

    Day 36 (post-vaccination)

  • Geometric Mean Fold-rise (GMFR) of Serum Neutralization Antibody Titers at Day 22

    SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. Fold-rise was calculated as the ratio of titer values of neutralizing antibodies post-vaccination (Day 22) and pre-vaccination (on Day 1) i.e., Day 22/Day 1.

    Day 1 (pre-vaccination) and Day 22 (post-vaccination)

  • Geometric Mean Fold-rise of Serum Neutralization Antibody Titers at Day 36

    SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. Fold-rise was calculated as the ratio of titer values of neutralizing antibodies post-vaccination (Day 36) and pre-vaccination (on Day 1) i.e., Day 36/Day 1.

    Day 1 (pre-vaccination) and Day 36 (post-vaccination)

  • Number of Participants With >=2-fold and >=4-fold Rise in Serum Neutralization Antibody Titers at Day 22

    SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. The fold rise (2-fold and 4-fold) was calculated as the ratio of titer values of neutralizing antibodies post-vaccination (on Day 22) and pre-vaccination (on Day 1) i.e., Day 22/Day 1.

    Day 1 (pre-vaccination) and Day 22 (post-vaccination)

  • Number of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titer at Day 36

    SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. The fold rise (2-fold and 4-fold) was calculated as the ratio of titer values of neutralizing antibodies post-vaccination (on Day 36) and pre-vaccination (on Day 1) i.e., Day 36/Day 1.

    Day 1 (pre-vaccination) and Day 36 (post-vaccination)

  • Percentage of Participants Achieving Seroconversion Against SARS-CoV-2 Virus Antigens at Day 22

    Seroconversion was defined as participants with a Baseline (Day 1) titer value below lower limit of quantification (LLOQ) with a detectable neutralization antibody titer above assay LLOQ post vaccination (at Day 22). LLOQ of the neutralization assay was a titer of 10.

    Day 22 (post-vaccination)

  • Percentage of Participants Achieving Seroconversion Against SARS-CoV-2 Virus Antigens at Day 36

    Seroconversion was defined as participants with a Baseline (Day 1) titer value below LLOQ with a detectable neutralization antibody titer above assay LLOQ post vaccination (at Day 36). LLOQ of the neutralization assay was a titer of 10.

    Day 36 (post-vaccination)

  • Number of Participants With Immediate Unsolicited Adverse Events (AEs)

    An AE was defined as any untoward medical occurrence in a participant who received study vaccine and does not necessary had to have a causal relationship with treatment. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions prelisted in the case report form (CRF) in terms of diagnosis and/or onset window post-vaccination. All participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurred during that time were recorded as immediate unsolicited AEs in the CRF. Reported AEs for each arm were presented as pre-specified in the study protocol.

    Within 30 minutes post any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 22])

  • Number of Participants With Solicited Injection Site Reactions

    A solicited reaction (SR) was defined as an "expected" adverse reaction (AR) (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the protocol and CRF and considered as related to vaccination. Solicited injection site reactions included pain, erythema and swelling. Reported AEs for each arm were presented as pre-specified in the study protocol.

    Within 7 days post any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 22])

  • Number of Participants With Solicited Systemic Reactions

    An SR was defined as an "expected" AR (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the protocol and CRF and considered as related to vaccination. Solicited systemic reactions included fever, headache, malaise and myalgia. Reported AEs for each arm were presented as pre-specified in the study protocol.

    Within 7 days post any and each vaccination (Vaccination 1 [i.e., Day 1] and 2 [i.e., Day 22])

  • Number of Participants With Unsolicited Adverse Events

    An AE was defined as any untoward medical occurrence in a participant who received study vaccine and does not necessary had to have a causal relationship with treatment. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions prelisted in the CRF in terms of diagnosis and/or onset post-vaccination. Reported AEs for each arm were presented as pre-specified in the study protocol.

    Within 21 days post any and each vaccination (Vaccination 1 [i.e., Day 1] and 2 [i.e., Day 22])

  • Number of Participants With Medically Attended Adverse Events (MAAE)

    A MAAE were AEs with a new onset or a worsening of a condition that prompted the participant to seek unplanned medical advice at a physician's office (including phone contact or email) or emergency department. An AE was defined as any untoward medical occurrence in a participant who received study vaccine and does not necessarily had to have a causal relationship with treatment. Reported AEs for each arm were presented as pre-specified in the study protocol.

    From Day 1 up to 12 months post last vaccination (i.e., up to Day 366 for Cohort 1 and up to Day 387 for Cohort 2)

  • Number of Participants With Serious Adverse Events (SAE)

    An SAE was any untoward medical occurrence 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. Reported AEs for each arm were presented as pre-specified in the study protocol.

    From Day 1 up to 12 months post last vaccination (i.e., up to Day 366 for Cohort 1 and up to Day 387 for Cohort 2)

  • Number of Participants With Adverse Events of Special Interest (AESIs)

    An AESI (serious or non-serious) was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate. Reported AEs for each arm were presented as pre-specified in the study protocol.

    From Day 1 up to 12 months post last vaccination (i.e., up to Day 366 for Cohort 1 and up to Day 387 for Cohort 2)

  • Number of Participants With Laboratory Test Results Based on US FDA Toxicity Grading Guidance

    Laboratory tests included hemoglobin (male and female), above and below normal white blood cell, lymphocytes, neutrophils \& eosinophils, platelet count, creatinine and blood urea nitrogen, hyponatremia \& hypernatremia, hyperkalemia \& hypokalemia, hyperglycemia (non-fasting), hypoproteinemia, alkaline phosphate, alanine aminotransferase, aspartate aminotransferase, bilirubin (with any increase in liver function test \[LFT\], bilirubin (normal in LFT), amylase \& lipase, Urine: protein, glucose \& blood. The US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adults and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" was used for grading. As per the guidance, Grade 1 = mild, Grade 2 = moderate and Grade 3 = severe.

    From Day 1 up to 8 days post last dose (i.e., up to Day 9 for Cohort 1 and up to Day 30 for Cohort 2)

Secondary Outcomes (10)

  • Geometric Mean Concentration (GMC) of Anti-S Binding Antibody at Day 1, 22, 36, 181, 202, 366 and 387

    Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 181 (only for Cohort 1), Day 202 (only for Cohort 2), Day 366 (only for Cohort 1), and Day 387 (only for Cohort 2)

  • Geometric Mean Fold-rise (GMFR) of Binding Antibody Concentration at Day 22, 36, 181, 202, 366 and 387

    Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 181 (only for Cohort 1), Day 202 (only for Cohort 2), Day 366 (only for Cohort 1), and Day 387 (only for Cohort 2)

  • Number of Participants With >=2-Fold and >=4- Fold Rise in Anti-S Binding Antibody Concentration at Day 22, 36, 181, 202, 366 and 387

    Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 181 (only for Cohort 1), Day 202 (only for Cohort 2), Day 366 (only for Cohort 1), and Day 387 (only for Cohort 2)

  • Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 181, 202, 366 and 387

    Cohort 1: Day 181 and Day 366 and Cohort 2: Day 202 and Day 387 (post-vaccination)

  • Geometric Mean Fold-rise of Serum Neutralization Antibody Titer at Day 181, 202, 366 and 387

    Day 1 (pre-vaccination), Cohort 1: Day 181 and Day 366 and Cohort 2: Day 202 and Day 387 (post-vaccination)

  • +5 more secondary outcomes

Study Arms (11)

Cohort 1: Group 1: SARS-CoV-2 vaccine LD + AF03

EXPERIMENTAL

Participants received a single intramuscular (IM) injection of SARS-CoV2 vaccine low-dose (LD) formulation along with adjuvant AF03 on Day 1.

Biological: CoV2 preS dTM-AF03 (low-dose)

Cohort 1: Group 2: SARS-CoV-2 vaccine LD + AS03

EXPERIMENTAL

Participants received a single IM injection of SARS-CoV2 vaccine LD formulation along with adjuvant AS03 on Day 1.

Biological: CoV2 preS dTM-AS03 (low-dose)

Cohort 1: Group 3: SARS-CoV-2 vaccine HD + AF03

EXPERIMENTAL

Participants received a single IM injection of SARS-CoV2 vaccine high-dose (HD) formulation along with adjuvant AF03 on Day 1.

Biological: CoV2 preS dTM-AF03 (high-dose)

Cohort 1: Group 4: SARS-CoV-2 vaccine HD + AS03

EXPERIMENTAL

Participants received a single IM injection of SARS-CoV2 vaccine HD formulation along with adjuvant AS03 on Day 1.

Biological: CoV2 preS dTM-AS03 (high-dose)

Cohort 1: Group 5: Placebo

PLACEBO COMPARATOR

Participants received an IM injection of placebo matching to SARS-CoV2 vaccine on Day 1.

Biological: Placebo (0.9% normal saline)

Cohort 2: Group 6: SARS-CoV-2 vaccine LD + AF03

EXPERIMENTAL

Participants received IM injection of SARS-CoV2 vaccine LD formulation along with adjuvant AF03 on Day 1 and Day 22, respectively.

Biological: CoV2 preS dTM-AF03 (low-dose)

Cohort 2: Group 7: SARS-CoV-2 vaccine LD + AS03

EXPERIMENTAL

Participants received IM injection of SARS-CoV2 vaccine LD formulation along with adjuvant AS03 on Day 1 and Day 22, respectively.

Biological: CoV2 preS dTM-AS03 (low-dose)

Cohort 2: Group 8: SARS-CoV-2 vaccine HD + AF03

EXPERIMENTAL

Participants received IM injection of SARS-CoV2 vaccine HD formulation along with adjuvant AF03 on Day 1 and Day 22, respectively.

Biological: CoV2 preS dTM-AF03 (high-dose)

Cohort 2: Group 9: SARS-CoV-2 vaccine HD + AS03

EXPERIMENTAL

Participants received IM injection of SARS-CoV2 vaccine HD formulation along with adjuvant AS03 on Day 1 and Day 22, respectively.

Biological: CoV2 preS dTM-AS03 (high-dose)

Cohort 2: Group 10: SARS-CoV-2 vaccine HD

EXPERIMENTAL

Participants received a single IM injection of SARS-CoV2 vaccine HD formulation without adjuvant on Day 1 and Day 22, respectively.

Biological: CoV2 preS dTM (high-dose) without adjuvant

Cohort 2: Group 11: Placebo

PLACEBO COMPARATOR

Participants received an IM injection of placebo matching to SARS-CoV2 on Day 1 and Day 22, respectively.

Biological: Placebo (0.9% normal saline)

Interventions

CoV2 preS dTM-AF03 (low-dose)BIOLOGICAL

Pharmaceutical form: liquid; route of administration: intramuscular injection

Cohort 1: Group 1: SARS-CoV-2 vaccine LD + AF03Cohort 2: Group 6: SARS-CoV-2 vaccine LD + AF03
CoV2 preS dTM-AF03 (high-dose)BIOLOGICAL

Pharmaceutical form: liquid; route of administration: intramuscular injection

Cohort 1: Group 3: SARS-CoV-2 vaccine HD + AF03Cohort 2: Group 8: SARS-CoV-2 vaccine HD + AF03
CoV2 preS dTM-AS03 (low-dose)BIOLOGICAL

Pharmaceutical form: liquid; route of administration: intramuscular injection

Cohort 1: Group 2: SARS-CoV-2 vaccine LD + AS03Cohort 2: Group 7: SARS-CoV-2 vaccine LD + AS03
CoV2 preS dTM-AS03 (high-dose)BIOLOGICAL

Pharmaceutical form: liquid; route of administration: intramuscular injection

Cohort 1: Group 4: SARS-CoV-2 vaccine HD + AS03Cohort 2: Group 9: SARS-CoV-2 vaccine HD + AS03
CoV2 preS dTM (high-dose) without adjuvantBIOLOGICAL

Pharmaceutical form: liquid; route of administration: intramuscular injection

Cohort 2: Group 10: SARS-CoV-2 vaccine HD
Placebo (0.9% normal saline)BIOLOGICAL

Pharmaceutical form: liquid; route of administration: intramuscular injection

Cohort 1: Group 5: PlaceboCohort 2: Group 11: Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Informed consent form had been signed and dated.
  • Able to attend all scheduled visits and complied with all study procedures.

You may not qualify if:

  • Participant was pregnant, or lactating, or of childbearing potential and not used an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 12 weeks after the last vaccination. To be considered of non-childbearing potential, a female was post-menopausal for at least 1 year or surgically sterile.
  • Receipt of any vaccine in the 30 days preceding the first study vaccination or planned receipt of any vaccine in the 30 days following the last study vaccination except for influenza vaccination, which might be received at least 2 weeks before and a minimum of 2 weeks after study vaccines.
  • Prior administration of a coronavirus vaccine SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome).
  • Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
  • History of SARS-CoV-2 infection, confirmed either clinically, serologically, or microbiologically
  • Chronic illness or condition considered to potentially increase the risk for severe COVID illness or that, in the opinion of the Investigator, was at a stage where it might interfere with study conduct or completion.
  • Receipt of any therapy known to had in-vitro antiviral activity against SARS-CoV-2 within 72 hours prior to the first blood drew.
  • Health care workers provided direct participant care for COVID-19 participants.
  • The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Investigational Site Number 8400004

Birmingham, Alabama, 35294, United States

Location

Investigational Site Number 8400012

Rolling Hills Estates, California, 90274, United States

Location

Investigational Site Number 8400011

Hollywood, Florida, 33024, United States

Location

Investigational Site Number 8400019

Melbourne, Florida, 32934, United States

Location

Investigational Site Number 8400016

Boston, Massachusetts, 02115, United States

Location

Investigational Site Number 8400002

Omaha, Nebraska, 68134, United States

Location

Investigational Site Number 8400001

Rochester, New York, 14609, United States

Location

Investigational Site Number 8400007

Rochester, New York, 14642, United States

Location

Investigational Site Number 8400008

Cleveland, Ohio, 44122, United States

Location

Investigational Site Number 8400003

Philadelphia, Pennsylvania, 19104, United States

Location

Investigational Site Number 8400014

Mt. Pleasant, South Carolina, 29464, United States

Location

Related Publications (2)

  • De Rosa SC, Cohen KW, Bonaparte M, Fu B, Garg S, Gerard C, Goepfert PA, Huang Y, Larocque D, McElrath MJ, Morris D, Van der Most R, de Bruyn G, Pagnon A. Whole-blood cytokine secretion assay as a high-throughput alternative for assessing the cell-mediated immunity profile after two doses of an adjuvanted SARS-CoV-2 recombinant protein vaccine candidate. Clin Transl Immunology. 2022 Jan 11;11(1):e1360. doi: 10.1002/cti2.1360. eCollection 2022.

    PMID: 35035955DERIVED

  • Goepfert PA, Fu B, Chabanon AL, Bonaparte MI, Davis MG, Essink BJ, Frank I, Haney O, Janosczyk H, Keefer MC, Koutsoukos M, Kimmel MA, Masotti R, Savarino SJ, Schuerman L, Schwartz H, Sher LD, Smith J, Tavares-Da-Silva F, Gurunathan S, DiazGranados CA, de Bruyn G. Safety and immunogenicity of SARS-CoV-2 recombinant protein vaccine formulations in healthy adults: interim results of a randomised, placebo-controlled, phase 1-2, dose-ranging study. Lancet Infect Dis. 2021 Sep;21(9):1257-1270. doi: 10.1016/S1473-3099(21)00147-X. Epub 2021 Apr 19.

    PMID: 33887209DERIVED

Related Links

MeSH Terms

Conditions

COVID-19

Interventions

Adjuvants, PharmaceuticSaline Solution

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutic AidsPharmaceutical PreparationsSpecialty Uses of ChemicalsChemical Actions and UsesCrystalloid SolutionsIsotonic SolutionsSolutions

Limitations and Caveats

Due to the limited number of COVID-19 cases before receiving an authorized/approved COVID-19 vaccine, the corresponding anti-nucleoprotein testing was not conducted, the planned few efficacy outcome measures data were not collected and analysis was not performed.

Results Point of Contact

Title
Trial Transparency Team
Organization
Sanofi Pasteur
Contact-US@sanofi.com
800-633-1610

Study Officials

  • Clinical Sciences & Operations

    Sanofi Pasteur, a Sanofi Company

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Participants, outcome assessors, Investigators, laboratory personnel, and the majority of Sponsor study staff will be blinded to vaccine group assignment; injection schedule will be unblinded and those preparing/administering the study interventions will be unblinded.
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: This was a parallel group prevention study. Participants from 2 age groups (adults 18 through 49 years of age and adults 50 years of age and older) received either 1 injection (Cohort 1) or 2 injections (Cohort 2) of study vaccine or placebo control. As a precautionary step, a sentinel safety cohort of 6 participants (younger adults only) within each dosing group from Cohort 1 was enrolled. An early safety data review was performed, including evaluation of safety data and laboratory measures to Day 9. Upon acceptable safety demonstrated from unblinded data review by limited members of the Sponsor Study Team, the remaining participants were enrolled simultaneously.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 2, 2020

First Posted

September 3, 2020

Study Start

September 3, 2020

Primary Completion

November 19, 2021

Study Completion

November 19, 2021

Last Updated

September 17, 2025

Results First Posted

June 22, 2023

Record last verified: 2023-05

Data Sharing

IPD Sharing
Will share

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

Locations

US(11)