COVID-19 Variant Immunologic Landscape Trial (COVAIL Trial)

NCT05289037 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 22-00045UM1AI148684-03
• Study Type: interventional
• Target: 1,270
• Locations: 1 country
• Sites: 22

Brief Summary

This phase 2 clinical trial will evaluate the safety and immunogenicity of additional doses of prototype and variant (alone or in combination) vaccine candidates in previously vaccinated participants with or without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and will evaluate innate, cellular, and humoral immune responses to inform on how to shift the immune response to cover new variants as they emerge. A randomized open-label, non-placebo controlled, multi-site, multi-stage clinical trial in individuals, 18 years of age and older, who are in a stable state of health, has received a complete authorized/approved vaccine series (primary series + booster either with homologous or heterologous vaccine products) \>/ = 16 weeks prior to enrollment. Subjects will be stratified by i) age (18-64 years and = 65 years of age) (however arms 16 and 17 or stage 4 will only enroll participants between the ages of 18-49 years) and ii) history of confirmed prior SARS-CoV-2 infection, and randomly assigned to receive one of several variant vaccines. Enrollment will target a goal of approximately 45% of each of the variant vaccine arms to be in older adults (= 65 years of age) for stages 1, 2 and 3 and approximately 20% to have had confirmed COVID-19 for all 4 stages. The primary objective is to evaluate humoral immune responses of candidate SARS-CoV-2 variant vaccines, alone or in combination.

Conditions

COVID-19

Keywords

Adaptive; COVAIL; Covid-19; Multivalent; Omicron; SARS-CoV-2; Vaccine; Variants

Outcome Measures

Primary Outcomes (43)

• Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against Wa-1 in One Dose Groups.

  Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against Wa-1. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported.

  Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against Wa-1 in Two Dose Group.

  Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against Wa-1. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported.

  Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against B.1.351 in One Dose Groups.

  Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against B.1.351. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported.

  Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against B.1.351 in Two Dose Group.

  Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against B.1.351. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported.

  Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against BA.1 in One Dose Groups.

  Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against BA.1. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported.

  Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against BA.1 in Two Dose Group.

  Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against BA.1. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported.

  Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against D614G in One Dose Groups.

  Pseudovirus Neutralization From Baseline Against D614G. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported.

  Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against D614G in Two Dose Group.

  Pseudovirus Neutralization From Baseline Against D614G. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported.

  Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.351 in One Dose Groups.

  Pseudovirus Neutralization From Baseline Against B.1.351. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported.

  Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.351 in Two Dose Group.

  Pseudovirus Neutralization From Baseline Against B.1.351. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported

  Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.617.2 in One Dose Groups.

  Pseudovirus Neutralization From Baseline Against B.1.617.2. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported

  Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.617.2 in Two Dose Group.

  Pseudovirus Neutralization From Baseline Against B.1.617.2. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported

  Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.1 in One Dose Groups.

  Pseudovirus Neutralization From Baseline Against BA.1. Fold-rise is calculated by dividing post-vaccination results by the baseline value The geometric mean of the fold rise is then reported

  Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.1 in Two Dose Group.

  Pseudovirus Neutralization From Baseline Against BA.1. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported.

  Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.2.12.1 in One Dose Groups.

  Pseudovirus Neutralization From Baseline Against BA.2.12.1. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported.

  Day 15

• Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.4/BA.5 in One Dose Groups.

  Pseudovirus Neutralization From Baseline Against BA.4/BA.5. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported.

  Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.4/BA.5 in Two Dose Group.

  Pseudovirus Neutralization From Baseline Against BA.4/BA.5. Fold-rise is calculated by dividing post-vaccination results by the baseline value. The geometric mean of the fold rise is then reported.

  Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean (GM) AUC of Antibody Against Wa-1 in One Dose Groups.

  Geometric Mean (GM) AUC of Antibody Against Wa-1. The assay result, reported in arbitrary units, was repeated over a series of dilutions (e.g. 1/10, 1/100, 1/1000). These data were plotted, with dilution factor (1/dilution) on the x-axis and assay result on the y-axis, and the AUC was calculated as the area under the assay results from each dilution. As the x-axis of this AUC calculation was the dilution factor and the y-axis was the assay result in arbitrary units, the calculated AUC has units of arbitrary units\*1/dilution.

  Day 1 Pre-Booster Dose, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean (GM) AUC of Antibody Against Wa-1 in Two Dose Group.

  Geometric Mean (GM) AUC of Antibody Against Wa-1. The assay result, reported in arbitrary units, was repeated over a series of dilutions (e.g. 1/10, 1/100, 1/1000). These data were plotted, with dilution factor (1/dilution) on the x-axis and assay result on the y-axis, and the AUC was calculated as the area under the assay results from each dilution. As the x-axis of this AUC calculation was the dilution factor and the y-axis was the assay result in arbitrary units, the calculated AUC has units of arbitrary units\*1/dilution.

  Day 1 Pre-Booster Dose, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean (GM) AUC of Antibody Against B.1.351 in One Dose Groups.

  Geometric Mean (GM) AUC of Antibody Against B.1.351. The assay result, reported in arbitrary units, was repeated over a series of dilutions (e.g. 1/10, 1/100, 1/1000). These data were plotted, with dilution factor (1/dilution) on the x-axis and assay result on the y-axis, and the AUC was calculated as the area under the assay results from each dilution. As the x-axis of this AUC calculation was the dilution factor and the y-axis was the assay result in arbitrary units, the calculated AUC has units of arbitrary units\*1/dilution.

  Day 1 Pre-Booster Dose, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean (GM) AUC of Antibody Against B.1.351 in Two Dose Group.

  Geometric Mean (GM) AUC of Antibody Against B.1.351. The assay result, reported in arbitrary units, was repeated over a series of dilutions (e.g. 1/10, 1/100, 1/1000). These data were plotted, with dilution factor (1/dilution) on the x-axis and assay result on the y-axis, and the AUC was calculated as the area under the assay results from each dilution. As the x-axis of this AUC calculation was the dilution factor and the y-axis was the assay result in arbitrary units, the calculated AUC has units of arbitrary units\*1/dilution.

  Day 1 Pre-Booster Dose, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean (GM) AUC of Antibody Against BA.1 in One Dose Groups.

  Geometric Mean (GM) AUC of Antibody Against BA.1. The assay result, reported in arbitrary units, was repeated over a series of dilutions (e.g. 1/10, 1/100, 1/1000). These data were plotted, with dilution factor (1/dilution) on the x-axis and assay result on the y-axis, and the AUC was calculated as the area under the assay results from each dilution. As the x-axis of this AUC calculation was the dilution factor and the y-axis was the assay result in arbitrary units, the calculated AUC has units of arbitrary units\*1/dilution.

  Day 1 Pre-Booster Dose, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean (GM) AUC of Antibody Against BA.1 in Two Dose Group.

  Geometric Mean (GM) AUC of Antibody Against BA.1. The assay result, reported in arbitrary units, was repeated over a series of dilutions (e.g. 1/10, 1/100, 1/1000). These data were plotted, with dilution factor (1/dilution) on the x-axis and assay result on the y-axis, and the AUC was calculated as the area under the assay results from each dilution. As the x-axis of this AUC calculation was the dilution factor and the y-axis was the assay result in arbitrary units, the calculated AUC has units of arbitrary units\*1/dilution.

  Day 1 Pre-Booster Dose, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean (GM) of Pseudovirus Neutralization Against D614G in One Dose Groups.

  Geometric Mean (GM) of Pseudovirus Neutralization Against D614G.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean (GM) of Pseudovirus Neutralization Against D614G in Two Dose Group.

  Geometric Mean (GM) of Pseudovirus Neutralization Against D614G.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.351 in One Dose Groups.

  Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.351.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.351 in Two Dose Group.

  Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.351.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.617.2 in One Dose Groups.

  Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.617.2.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.617.2 in Two Dose Group.

  Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.617.2.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean (GM) of Pseudovirus Neutralization Against BA.1 in One Dose Groups.

  Geometric Mean (GM) of Pseudovirus Neutralization Against BA.1.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean (GM) of Pseudovirus Neutralization Against BA.1 in Two Dose Group.

  Geometric Mean (GM) of Pseudovirus Neutralization Against BA.1.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean (GM) of Pseudovirus Neutralization Against BA.2.12.1 in One Dose Groups.

  Geometric Mean (GM) of Pseudovirus Neutralization Against BA.2.12.1.

  Day 1 Pre-Booster Dose, Day 15

• Geometric Mean (GM) of Pseudovirus Neutralization Against BA.4/BA.5 in One Dose Groups.

  Geometric Mean (GM) of Pseudovirus Neutralization Against BA.4/BA.5.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean (GM) of Pseudovirus Neutralization Against BA.4/BA.5 in Two Dose Group.

  Geometric Mean (GM) of Pseudovirus Neutralization Against BA.4/BA.5.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.351 in One Dose Groups.

  GMR to D614G variant of Pseudovirus Neutralization Against B.1.351. GMR is calculated by dividing by the neutralization against D614G. The geometric mean of the ratio is then reported.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.351 in Two Dose Group.

  GMR to D614G variant of Pseudovirus Neutralization Against B.1.351. GMR is calculated by dividing by the neutralization against D614G. The geometric mean of the ratio is then reported.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.617.2 in One Dose Groups.

  GMR to D614G variant of Pseudovirus Neutralization Against B.1.617.2. GMR is calculated by dividing by the neutralization against D614G. The geometric mean of the ratio is then reported.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.617.2 in Two Dose Group.

  GMR to D614G variant of Pseudovirus Neutralization Against B.1.617.2. GMR is calculated by dividing by the neutralization against D614G. The geometric mean of the ratio is then reported.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.1 in One Dose Groups.

  GMR to D614G variant of Pseudovirus Neutralization Against BA.1. GMR is calculated by dividing by the neutralization against D614G. The geometric mean of the ratio is then reported.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.1 in Two Dose Group.

  GMR to D614G variant of Pseudovirus Neutralization Against BA.1. GMR is calculated by dividing by the neutralization against D614G. The geometric mean of the ratio is then reported.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

• Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.2.12.1 in One Dose Groups.

  GMR to D614G variant of Pseudovirus Neutralization Against BA.2.12.1. GMR is calculated by dividing by the neutralization against D614G. The geometric mean of the ratio is then reported.

  Day 1 Pre-Booster Dose, Day 15

• Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.4/BA.5 in One Dose Groups.

  GMR to D614G variant of Pseudovirus Neutralization Against BA.4/BA.5. GMR is calculated by dividing by the neutralization against D614G. The geometric mean of the ratio is then reported.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

• Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.4/BA.5 in Two Dose Group.

  GMR to D614G variant of Pseudovirus Neutralization Against BA.4/BA.5. GMR is calculated by dividing by the neutralization against D614G. The geometric mean of the ratio is then reported.

  Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

Secondary Outcomes (8)

• Frequency of Any Adverse Events (AEs) Leading to Withdrawal From the Study.

  Day 1 to study completion (through up to Day 366) for Arms 1,2,4,5,6,7,8,9,10,11,12,13,14,15,16,17 and Day 1 to study completion (through up to Day 422) for Arm 3.

• Frequency of Any Adverse Events of Special Interest (AESIs)

  Day 1 to study completion (through up to Day 366) for Arms 1,2,4,5,6,7,8,9,10,11,12,13,14,15,16,17 and Day 1 to study completion (through up to Day 422) for Arm 3.

• Frequency of Any Medically Attended Adverse Events (MAAEs)

  Day 1 to study completion (through up to Day 366) for Arms 1,2,4,5,6,7,8,9,10,11,12,13,14,15,16,17 and Day 1 to study completion (through up to Day 422) for Arm 3.

• Frequency of Any New Onset Chronic Medical Conditions (NOCMCs)

  Day 1 to study completion (through up to Day 366) for Arms 1,2,4,5,6,7,8,9,10,11,12,13,14,15,16,17 and Day 1 to study completion (through up to Day 422) for Arm 3.

• Frequency of Any Serious Adverse Events (SAEs)

  Day 1 to study completion (through up to Day 366) for Arms 1,2,4,5,6,7,8,9,10,11,12,13,14,15,16,17 and Day 1 to study completion (through up to Day 422) for Arm 3.

Study Arms (17)

Arm 01

EXPERIMENTAL

mRNA-1273 administered through 0.2 mg/ml intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=100

Biological: mRNA-1273; Other: Sodium Chloride, 0.9%

Arm 02

EXPERIMENTAL

0.1 mg/ml of mRNA-1273.351 and 0.2 mg/ml of mRNA-1273.529 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=100

Biological: mRNA-1273.351; Biological: mRNA-1273.529; Other: Sodium Chloride, 0.9%

Arm 03

EXPERIMENTAL

0.1 mg/ml of mRNA-1273.351 and 0.2 mg/ml of mRNA-1273.529 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 and Day 57 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=100

Biological: mRNA-1273.351; Biological: mRNA-1273.529; Other: Sodium Chloride, 0.9%

Arm 04

EXPERIMENTAL

0.2 mg/ml of mRNA-1273.617.2 and 0.2 mg/ml of mRNA-1273.529 administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=100

Biological: mRNA-1273.529; Biological: mRNA-1273.617.2; Other: Sodium Chloride, 0.9%

Arm 05

EXPERIMENTAL

0.2 mg/ml of mRNA-1273.529 administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=100

Biological: mRNA-1273.529; Other: Sodium Chloride, 0.9%

Arm 06

EXPERIMENTAL

0.2 mg/ml of mRNA-1273.529 and mRNA-1273 0.2 mg/ml administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=100

Biological: mRNA-1273; Biological: mRNA-1273.529; Other: Sodium Chloride, 0.9%

Arm 07

EXPERIMENTAL

500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50

Biological: BNT162b2

Arm 08

EXPERIMENTAL

500 mcg/mL of BNT162b2 (Beta) and 500 mcg/mL of BNT162b2 (Omicron) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50

Biological: BNT162b2 (B.1.1.529); Biological: BNT162b2 (B.1.351)

Arm 09

EXPERIMENTAL

500 mcg/mL of BNT162b2 (Omicron) administered through intramuscular injection in the deltoid muscle on Day 1 and Day 57 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50

Biological: BNT162b2 (B.1.1.529)

Arm 10

EXPERIMENTAL

500 mcg/mL of BNT162b2 (Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50

Biological: BNT162b2 (B.1.351)

Arm 11

EXPERIMENTAL

500 mcg/mL of BNT162b2 (Beta) and 500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50

Biological: BNT162b2; Biological: BNT162b2 (B.1.351)

Arm 12

EXPERIMENTAL

500 mcg/mL of BNT162b2 (Omicron) and 500 mcg/mL of BNT162b2 (Wildtype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50

Biological: BNT162b2; Biological: BNT162b2 (B.1.1.529)

Arm 13

EXPERIMENTAL

500 mcg/mL CoV2 preS dTM-AS03 \[D614\] (prototype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50

Drug: AS03; Biological: CoV2 preS dTM/D614

Arm 14

EXPERIMENTAL

500 mcg/mL CoV2 preS dTM-AS03 \[B.1.351\] (Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50

Drug: AS03; Biological: CoV2 preS dTM [B.1.351]

Arm 15

EXPERIMENTAL

500 mcg/mL CoV2 preS dTM-AS03 \[D614 + B.1.351\] (prototype + Beta) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 64; \> / = 65 years (\~45% in \> / = 65 years) N=50

Drug: AS03; Biological: CoV2 preS dTM/D614+B.1.351

Arm 16

EXPERIMENTAL

100 mcg/mL BNT162b2 bivalent (wildtype and Omicron BA.1) + Wildtype (Prototype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 49 years; ( 45% in \> / = 49 years) N=100

Biological: BNT162b2 bivalent (wildtype and Omicron BA.1)

Arm 17

EXPERIMENTAL

100 mcg/mL BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5) + Wildtype (Prototype) administered through intramuscular injection in the deltoid muscle on Day 1 in participants from 18 to 49 years; ( 45% in \> / = 49 years) N=100

Biological: BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5)

Interventions

AS03 DRUG

AS03 oil-in-water emulsion adjuvant.

Arm 13; Arm 14; Arm 15

BNT162b2 BIOLOGICAL

A nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2.

Arm 07; Arm 11; Arm 12

BNT162b2 (B.1.1.529) BIOLOGICAL

A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.

Arm 08; Arm 09; Arm 12

BNT162b2 (B.1.351) BIOLOGICAL

A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer contains mRNA that encodes for the prefusion stabilized S protein of the B.1.351 (Beta) variant SARS-CoV-2 strain.

Arm 08; Arm 10; Arm 11

BNT162b2 bivalent (wildtype and Omicron BA.1) BIOLOGICAL

A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer. Contains mRNA that encodes for the prefusion stabilized S protein of the Omicron BA.1 variant SARS-CoV-2 strain and the ancestral strain of SARS-CoV-2.

Arm 16

BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5) BIOLOGICAL

A preservative-free, sterile dispersion of RNA formulated in LNP in aqueous cryoprotectant buffer. Contains mRNA that encodes for the prefusion stabilized S protein of the Omicron BA.4/BA.5 variant SARS-CoV-2 strain and the ancestral strain of SARS-CoV-2.

Arm 17

CoV2 preS dTM [B.1.351] BIOLOGICAL

Is a liquid formulation made of recombinant protein placed in a formulation buffer that contains the spike protein sequence of the B.1.351 (Beta) variant SARS-CoV-2 strain.

Arm 14

CoV2 preS dTM/D614 BIOLOGICAL

Is a liquid formulation made of recombinant protein placed in a formulation buffer. The antigen solution contains the spike protein sequence of the ancestral strain of SARS-CoV-2.

Arm 13

CoV2 preS dTM/D614+B.1.351 BIOLOGICAL

Is a liquid formulation made of recombinant protein placed in a formulation buffer contains the spike protein sequences of the ancestral and B.1.351 (Beta) variant SARS-CoV-2 strains

Arm 15

mRNA-1273 BIOLOGICAL

Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized spike (S) protein of the 2019 novel coronavirus (2019-nCoV).

Arm 01; Arm 06

mRNA-1273.351 BIOLOGICAL

Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the pre fusion stabilized spike (S) protein of the B.1.351 variant SARS-CoV-2 strain.

Arm 02; Arm 03

mRNA-1273.529 BIOLOGICAL

Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.1.529 (Omicron) variant SARS-CoV-2 strain.

Arm 02; Arm 03; Arm 04; Arm 05; Arm 06

mRNA-1273.617.2 BIOLOGICAL

Lipid nanoparticle (LNP) dispersion containing an mRNA that encodes for the prefusion stabilized S protein of the B.1.617.2 (Delta) variant SARS-CoV-2 strain.

Arm 04

Sodium Chloride, 0.9% OTHER

0.9% Sodium Chloride Injection

Arm 01; Arm 02; Arm 03; Arm 04; Arm 05; Arm 06

Eligibility Criteria

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

You may qualify if:

• Participants must meet all of the following criteria to be eligible to participate in this study:
• Individuals \> / = 18 years of age at the time of consent. (18-49 years for stage 4).
• Confirmed receipt of a complete primary and booster COVID-19 vaccine series, either homologous or heterologous, with an FDA authorized/approved vaccine at least 16 weeks prior to study vaccine dose 1.
• Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests and other study procedures.
• Determined by medical history, targeted physical examination and clinical judgement of the investigator to be in stable state of health.
• Note: Participants with pre-existing stable chronic medical conditions defined as condition not requiring significant change in therapy or hospitalization for worsening disease within 4 weeks from enrollment, can be included at the discretion of the investigator.

You may not qualify if:

• Participants meeting any of the following criteria will be excluded from the study:
• Confirmed SARS-CoV-2 infection \< 16 weeks prior to any study vaccine dose.
• Pregnant and breastfeeding participants.
• Prior administration of an investigational coronavirus vaccine at any time or SARS-CoV-2 immunoglobulin, monoclonal antibody or plasma antibody therapy in the preceding 3 months.
• Note: subjects that participated in clinical trials of products that are now FDA approved/authorized are allowed to participate.
• Current/planned simultaneous participation in another interventional study or receipt of any investigational study product within 28 days prior to vaccine study dose(s).
• A history of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a vaccine, polyethylene glycol (PEG), polysorbate or nanolipid particles.
• A history of myocarditis or pericarditis at any time prior to enrollment (for subjects in stages 1, 2 and 4).
• Received or plans to receive a vaccine within 28 days prior to or after any dose of study vaccine.
• Note: Receipt of seasonal influenza vaccine is allowed at any time.
• Bleeding disorder diagnosed by a healthcare provider (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or bleeding difficulties with intramuscular injections or blood draws.
• Current or previous diagnosis of an immunocompromising condition or other immunosuppressive condition.
• Advanced liver or kidney diseases.
• Advanced (CD4 count \< 200) and/or untreated HIV, untreated Hepatitis B or untreated Hepatitis C.
• Received oral, intramuscular or intravenous systemic immunosuppressants, or immune-modifying drugs for \>14 days in total within 6 months prior to any study vaccine dose (for corticosteroids = 20 mg \> / = day of prednisone equivalent).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (22)

University of Alabama at Birmingham School of Medicine - Alabama Vaccine Research Clinic

Birmingham, Alabama, 35294, United States

Location

University of California, San Diego (UCSD) - Antiviral Research Center (AVRC)

San Diego, California, 92103-8208, United States

Location

Zuckerberg San Francisco General Hospital, UCSF Positive Health Program

San Francisco, California, 94110, United States

Location

George Washington University Medical Faculty Associates

Washington D.C., District of Columbia, 20037-3201, United States

Location

Howard University - Department of Medicine - Division of Infectious Disease

Washington D.C., District of Columbia, 20060, United States

Location

Morehouse School of Medicine - Clinical Research Center

Atlanta, Georgia, 30310, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322-1013, United States

Location

The Hope Clinic of Emory University

Decatur, Georgia, 30030-1705, United States

Location

University of Illinois at Chicago College of Medicine - Division of Infectious Diseases

Chicago, Illinois, 60612, United States

Location

University of Iowa Hospitals & Clinics - Department of Internal Medicine

Iowa City, Iowa, 52242, United States

Location

Tulane University Clinical Translational Unit

New Orleans, Louisiana, 70112, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115-6110, United States

Location

Saint Louis University Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

Washington University School of Medicine in St. Louis - Infectious Disease Clinical Research Unit

St Louis, Missouri, 63110, United States

Location

NYU Grossman School, NYU Langone Vaccine Center, Long Island

Mineola, New York, 11501, United States

Location

NYU Langone Vaccine Center Research Clinic, Manhattan

New York, New York, 10016, United States

Location

University of Rochester Medical Center - Vaccine Research Unit

Rochester, New York, 14611-3201, United States

Location

Duke Vaccine and Trials Unit

Durham, North Carolina, 27703, United States

Location

Baylor College of Medicine

Houston, Texas, 77030-3411, United States

Location

University of Texas Medical Branch

League City, Texas, 77573, United States

Location

Kaiser Permanente Washington Health Research Institute

Seattle, Washington, 98101, United States

Location

The University of Washington - Virology Research Clinic

Seattle, Washington, 98104, United States

Location

Related Publications (5)

• Diemert DJ, Graciaa DS, Zhang B, Rouphael NG, Branche AR, Martin TCS, Jackson LA, Presti RM, Kamidani S, Mahgoub SM, Babu TM, Magaret CA, Simon V, van Bakel H, Roberts PC, Beigel JH, Gilbert PB, Follmann D; Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study Team. Effect of Omicron BA.1-based compared to prototype booster mRNA vaccination on incidence of COVID-19 in the COVAIL trial. Vaccine. 2025 Oct 3;64:127718. doi: 10.1016/j.vaccine.2025.127718. Epub 2025 Sep 9.

  PMID: 40930044 DERIVED

• Fong Y, Dang L, Zhang B, Fintzi J, Chen S, Wang J, Rouphael NG, Branche AR, Diemert DJ, Falsey AR, Losada C, Baden LR, Frey SE, Whitaker JA, Little SJ, Kamidani S, Walter EB, Novak RM, Rupp R, Jackson LA, Yu C, Magaret CA, Molitor C, Borate B, Babu TM, Kottkamp AC, Luetkemeyer AF, Immergluck LC, Presti RM, Backer M, Winokur PL, Mahgoub SM, Goepfert PA, Fusco DN, Atmar RL, Posavad CM, Mu J, Makowski M, Makhene MK, Nayak SU, Roberts PC, Follmann D, Gilbert PB; Coronavirus Variant Immunologic Landscape Trial (COVAIL) Study Team. Neutralizing Antibody Immune Correlates for a Recombinant Protein Vaccine in the COVAIL Trial. Clin Infect Dis. 2025 Feb 5;80(1):223-227. doi: 10.1093/cid/ciae465.

  PMID: 39325506 DERIVED

• Branche AR, Rouphael NG, Diemert DJ, Falsey AR, Losada C, Baden LR, Frey SE, Whitaker JA, Little SJ, Anderson EJ, Walter EB, Novak RM, Rupp R, Jackson LA, Babu TM, Kottkamp AC, Luetkemeyer AF, Immergluck LC, Presti RM, Backer M, Winokur PL, Mahgoub SM, Goepfert PA, Fusco DN, Malkin E, Bethony JM, Walsh EE, Graciaa DS, Samaha H, Sherman AC, Walsh SR, Abate G, Oikonomopoulou Z, El Sahly HM, Martin TCS, Kamidani S, Smith MJ, Ladner BG, Porterfield L, Dunstan M, Wald A, Davis T, Atmar RL, Mulligan MJ, Lyke KE, Posavad CM, Meagher MA, Stephens DS, Neuzil KM, Abebe K, Hill H, Albert J, Telu K, Mu J, Lewis TC, Giebeig LA, Eaton A, Netzl A, Wilks SH, Tureli S, Makhene M, Crandon S, Montefiori DC, Makowski M, Smith DJ, Nayak SU, Roberts PC, Beigel JH; COVAIL Study Group. Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial. Nat Med. 2023 Sep;29(9):2334-2346. doi: 10.1038/s41591-023-02503-4. Epub 2023 Aug 28.

  PMID: 37640860 DERIVED

• Branche A, Rouphael N, Diemert D, Falsey A, Losada C, Baden LR, Frey S, Whitaker J, Little S, Anderson E, Walter E, Novak R, Rupp R, Jackson L, Babu T, Kottkamp A, Luetkemeyer A, Immergluck L, Presti R, Backer M, Winokur P, Mahgoub S, Goepfert P, Fusco D, Malkin E, Bethony J, Walsh E, Graciaa D, Samaha H, Sherman A, Walsh S, Abate G, Oikonomopoulou Z, El Sahly H, Martin T, Kamidani S, Smith M, Ladner B, Porterfield L, Dunstan M, Wald A, Davis T, Atmar R, Mulligan M, Lyke K, Posavad C, Meagher M, Stephens D, Neuzil K, Abebe K, Hill H, Albert J, Telu K, Mu J, Lewis T, Giebeig L, Eaton A, Netzl A, Wilks S, Tureli S, Makhene M, Crandon S, Montefiori D, Makowski M, Smith D, Nayak S, Roberts P, Beigel J. Bivalent and Monovalent SARS-CoV-2 Variant Vaccine Boosters Improve coverage of the known Antigenic Landscape: Results of the COVID-19 Variant Immunologic Landscape (COVAIL) Trial. Res Sq [Preprint]. 2023 May 5:rs.3.rs-2653179. doi: 10.21203/rs.3.rs-2653179/v1.

  PMID: 37205592 DERIVED

• Branche AR, Rouphael NG, Diemert DJ, Falsey AR, Losada C, Baden LR, Frey SE, Whitaker JA, Little SJ, Anderson EJ, Walter EB, Novak RM, Rupp R, Jackson LA, Babu TM, Kottkamp AC, Luetkemeyer AF, Immergluck LC, Presti RM, Backer M, Winokur PL, Mahgoub SM, Goepfert PA, Fusco DN, Malkin E, Bethony JM, Walsh EE, Graciaa DS, Samaha H, Sherman AC, Walsh SR, Abate G, Oikonomopoulou Z, El Sahly HM, Martin TCS, Rostad CA, Smith MJ, Ladner BG, Porterfield L, Dunstan M, Wald A, Davis T, Atmar RL, Mulligan MJ, Lyke KE, Posavad CM, Meagher MA, Stephens DS, Neuzil KM, Abebe K, Hill H, Albert J, Lewis TC, Giebeig LA, Eaton A, Netzl A, Wilks SH, Tureli S, Makhene M, Crandon S, Lee M, Nayak SU, Montefiori DC, Makowski M, Smith DJ, Roberts PC, Beigel JH; COVAIL Study Group. SARS-CoV-2 Variant Vaccine Boosters Trial: Preliminary Analyses. medRxiv [Preprint]. 2022 Jul 15:2022.07.12.22277336. doi: 10.1101/2022.07.12.22277336.

  PMID: 35898343 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

BNT162 Vaccine; 2019-nCoV Vaccine mRNA-1273; Sodium Chloride

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

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Nadine Rouphael, MD
• Organization: The Hope Clinic of Emory University

nroupha@emory.edu

404-712-1435

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2022
• First Posted: March 21, 2022
• Study Start: March 30, 2022
• Primary Completion: November 22, 2023
• Study Completion: November 27, 2023
• Last Updated: October 20, 2025
• Results First Posted: March 14, 2025

Record last verified: 2022-10-03

Locations

US (22)