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

Phase 2

Completed

Conditions: COVID-19

Interventions: 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

Registration Number: NCT04762680

Lead Sponsor: Sanofi Pasteur, a Sanofi Company

Brief Summary: 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.

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 3159

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2 Cohort -SARS-CoV-2 vaccine Formulation 1	SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 1	2 injections of SARS-CoV-2 vaccine Formulation 1 at Day 1 and Day 22
Phase 2 Cohort - SARS-CoV-2 vaccine Formulation 2	SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 2	2 injections of SARS-CoV-2 vaccine Formulation 2 at Day 1 and Day 22
Phase 2 Cohort - SARS-CoV-2 vaccine Formulation 3	SARS-CoV-2 recombinant protein vaccine Phase 2 Formulation 3	2 injections of SARS-CoV-2 vaccine Formulation 3 Day 1 and Day 22
Supplemental Cohort 1 - Booster Monovalent (D614)-AS03 SARS-CoV-2 vaccine	SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (D614)-AS03, Dosage A	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
Supplemental Cohort 2 - Booster Monovalent (B.1.351)-AS03 SARS-CoV-2 vaccine	SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03	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
Supplemental Cohort 2 - Booster Bivalent (D614 + B.1.351)-AS03 SARS-CoV-2 vaccine	SARS-CoV-2 adjuvanted recombinant protein vaccine, bivalent (D614+B.1.351)-AS03	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
Supplemental Cohort 2 - Booster Monovalent (D614)-AS03 SARS-CoV-2 vaccine	SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (D614)-AS03, Dosage A	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
Supplemental Comparator for Cohort 1 and 2 Boosters - Monovalent (D614)-AS03 SARS-CoV-2 vaccine	SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (D614)-AS03, Dosage B	2 injections of monovalent (D614)-AS03 SARS-CoV-2 vaccine at Day 1 and Day 22 in previously unvaccinated, naïve participants
Cohort 2 - Booster Exploratory 1	SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 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
Cohort 2 - Booster Exploratory 2	SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 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
Cohort 2 - Booster Exploratory 3	SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 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
Cohort 2 - Booster Exploratory 4	SARS-CoV-2 adjuvanted recombinant protein vaccine, monovalent (B.1.351)-AS03 Alternative Exploratory Formulation 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

Primary Outcome Measures

Name	Time	Method
Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Number of Participants With Immediate Unsolicited Adverse Events (AEs)	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)	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.
Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Number of Participants With Solicited Injection Site Reactions and Systemic 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)	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.
Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Number of Participants With Unsolicited Adverse Events	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)	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.
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)	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.	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: Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) D614G Strain at Day 1	Pre-vaccination on 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.
Phase 2: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain at Day 36	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.
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	Day 1 (pre-vaccination) and 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.
Phase 2: Number of Responders as Determined by Neutralizing Antibody Titers Against SARS-CoV-2 D614G Strain at Day 36	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.
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	Pre-vaccination on 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.
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	Cohorts 1 and 2: 14 days post-vaccination on Day 1, Day 15; Comparator: 14 days post-vaccination on Day 22, Day 36	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.
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	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.

Secondary Outcome Measures

Name	Time	Method
Phase 2: Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 D614G Strain at Days 22, 78, 134, 202, 292, and 387	Post-vaccination on 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.
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	Pre-vaccination on Day 1 and Post-vaccination on 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.
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	Post-vaccination on 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).
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	Pre-vaccination on Day 1 and post-vaccination on Days 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.
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	Pre-vaccination on Day 1 and Post-vaccination on 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.
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	Post-vaccination on 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.
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	Post-vaccination on 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.
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	Pre-vaccination on Day 1 and Post-vaccination on 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.
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	Cohorts 1 and 2: 14 days post-vaccination on Day 1 (Day 15); Comparator: 14 days post-vaccination on Day 22 (Day 36)	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.
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	Pre-vaccination on Day 1 and post-vaccination on Days 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.
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	Pre-vaccination on Day 1 and Post-vaccination on 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.
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	Pre-vaccination on Day 1 and post-vaccination on Days 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.
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	Pre-vaccination on Day 1 and Post-vaccination on 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.
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	Pre-vaccination on Day 1 and post-vaccination on 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 the neutralization assay (monogram assay) and the results were expressed as geometric mean titers.
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	Pre-vaccination on Day 1 and Post-vaccination on 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.
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	Pre-vaccination on Day 1 and post-vaccination on Days 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.
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	Pre-vaccination on Day 1 and Post-vaccination on 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.
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	Post-vaccination on 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.
Phase 2: Percentage of Participants With Serologically-Confirmed SARS-CoV-2 Infection	From first dose of study vaccine administration (Day 1) up to 387 days	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.
Phase 2 and Phase 3 (Cohorts 1, 2 and Comparator): Percentage of Participants With Laboratory-Confirmed Symptomatic COVID-19	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.	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 (Cohorts 1, 2 and Comparator): Percentage of Participants With Symptomatic COVID-19 Episodes Associated With Hospitalization	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.	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 (Cohorts 1, 2 and Comparator): Percentage of Participants With Severe Symptomatic COVID-19	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.	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 (Cohorts 1, 2 and Comparator): Percentage of Participants With Death Associated With Symptomatic COVID-19	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.	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.

Trial Locations

Locations (66): Synexus - Clinical Research Advantage, Inc. Site Number : 8400270
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Birmingham, Alabama, United States
Synexus Chandler Site Number : 8400251
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Chandler, Arizona, United States
Synexus - Glendale. Site Number : 8400271
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Glendale, Arizona, United States
Baptist Health Center for Clinical Research Site Number : 8400077
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Little Rock, Arkansas, United States
Charles R. Drew University of Medicine and Science Site Number : 8400220
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Los Angeles, California, United States
Peninsula Research Associates, Inc. Site Number : 8400094
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Rolling Hills Estates, California, United States
Optimal Research Site Number : 8400173
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San Diego, California, United States
Yale University Site Number : 8400239
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New Haven, Connecticut, United States
The George Washington University Site Number : 8400212
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Washington D.C., District of Columbia, United States
Cenexel Research Centers of America Site Number : 8400089
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Hollywood, Florida, United States
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Synexus - Clinical Research Advantage, Inc. Site Number : 8400270
🇺🇸Birmingham, Alabama, United States