MedPath

COVID-19 Variant Immunologic Landscape Trial (COVAIL Trial)

Phase 2
Completed
Conditions
COVID-19
Interventions
Biological: BNT162b2 (B.1.1.529)
Biological: BNT162b2 bivalent (wildtype and Omicron BA.1)
Biological: BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5)
Other: Sodium Chloride, 0.9%
Biological: BNT162b2 (B.1.351)
Biological: CoV2 preS dTM/D614
Biological: CoV2 preS dTM [B.1.351]
Biological: CoV2 preS dTM/D614+B.1.351
Registration Number
NCT05289037
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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.

Detailed Description

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. This is an adaptive design and may add arms of new vaccine platforms and/or variant lineage spike vaccines as needed. The study arms will be conducted in different stages (that could overlap) depending on public health needs and the availability of study products (starting with the available mRNA vaccines). The primary objective is to evaluate humoral immune responses of candidate SARS-CoV-2 variant vaccines, alone or in combination. The secondary objective is to evaluate the safety of candidate SARS-CoV-2 variant vaccines, as assessed by: a) Local and systemic solicited Adverse Events for 7 days following each vaccine dose; b) Unsolicited Adverse Events from Dose 1 to 28 days following each vaccine dose; c) Serious Adverse Events (SAEs), Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interests (AESIs), New Onset of Chronic Medical (NOCMCs) and Adverse Events (AEs) leading to withdrawal from the study from Dose 1 to 12 months after last vaccine dose.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1270
Inclusion Criteria

Participants must meet all of the following criteria to be eligible to participate in this study:

  1. Individuals > / = 18 years of age at the time of consent. (18-49 years for stage 4).
  2. 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.
  3. Willing and able to comply with all scheduled visits, vaccination plan, laboratory tests and other study procedures.
  4. 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.

Exclusion Criteria

Participants meeting any of the following criteria will be excluded from the study:

  1. Confirmed SARS-CoV-2 infection < 16 weeks prior to any study vaccine dose.

  2. Pregnant and breastfeeding participants.

  3. 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.

  4. Current/planned simultaneous participation in another interventional study or receipt of any investigational study product within 28 days prior to vaccine study dose(s).

  5. 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.

  6. A history of myocarditis or pericarditis at any time prior to enrollment (for subjects in stages 1, 2 and 4).

  7. 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.

  8. 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.

  9. Current or previous diagnosis of an immunocompromising condition or other immunosuppressive condition.

  10. Advanced liver or kidney diseases.

  11. Advanced (CD4 count < 200) and/or untreated HIV, untreated Hepatitis B or untreated Hepatitis C.

  12. 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).

    Note: Topical medications are allowed.

  13. Received immunoglobulin or blood-derived products, within 3 months prior any study vaccine dose.

  14. Received chemotherapy, immunotherapy or radiation therapy within 6 months prior to any study vaccine dose.

  15. Study personnel or an immediate family member or household member of study personnel.

  16. Is acutely ill or febrile 72 hours prior to or at vaccine dosing (fever defined as > / = 38.0 degrees Celsius/100.4 degrees Fahrenheit). Participants meeting this criterion may be rescheduled within the relevant window periods.

    Note: Afebrile participants with minor illnesses can be enrolled at the discretion of the Investigator, as long as the illness is not suggestive of COVID-19.

  17. Plan to receive a COVID-19 booster vaccine outside of the study within the next 180 days. (for subjects in Stage 4 only)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 01Sodium Chloride, 0.9%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
Arm 02mRNA-1273.3510.1 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
Arm 02Sodium Chloride, 0.9%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
Arm 01mRNA-1273mRNA-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
Arm 03mRNA-1273.5290.1 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
Arm 03Sodium Chloride, 0.9%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
Arm 04mRNA-1273.5290.2 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
Arm 08BNT162b2 (B.1.351)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
Arm 09BNT162b2 (B.1.1.529)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
Arm 04Sodium Chloride, 0.9%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
Arm 05mRNA-1273.5290.2 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
Arm 05Sodium Chloride, 0.9%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
Arm 06Sodium Chloride, 0.9%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
Arm 07BNT162b2500 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
Arm 08BNT162b2 (B.1.1.529)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
Arm 10BNT162b2 (B.1.351)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
Arm 11BNT162b2500 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
Arm 11BNT162b2 (B.1.351)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
Arm 12BNT162b2500 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
Arm 12BNT162b2 (B.1.1.529)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
Arm 13AS03500 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
Arm 13CoV2 preS dTM/D614500 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
Arm 14AS03500 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
Arm 14CoV2 preS dTM [B.1.351]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
Arm 15CoV2 preS dTM/D614+B.1.351500 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
Arm 16BNT162b2 bivalent (wildtype and Omicron BA.1)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
Arm 17BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5)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
Arm 15AS03500 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
Arm 02mRNA-1273.5290.1 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
Arm 03mRNA-1273.3510.1 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
Arm 04mRNA-1273.617.20.2 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
Arm 06mRNA-12730.2 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
Arm 06mRNA-1273.5290.2 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
Primary Outcome Measures
NameTimeMethod
Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against Wa-1 in One Dose Groups.Day 29, Day 91, Day 181, Day 271, Day 366

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.

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

Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against B.1.351 in One Dose Groups.Day 29, Day 91, Day 181, Day 271, Day 366

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.

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

Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against BA.1 in One Dose Groups.Day 29, Day 91, Day 181, Day 271, Day 366

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.

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

Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against D614G in One Dose Groups.Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

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.

Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against D614G in Two Dose Group.Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

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.

Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.351 in One Dose Groups.Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

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.

Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.351 in Two Dose Group.Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

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

Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.617.2 in One Dose Groups.Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

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

Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.617.2 in Two Dose Group.Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

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

Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.1 in One Dose Groups.Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

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

Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.1 in Two Dose Group.Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

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.

Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.2.12.1 in One Dose Groups.Day 15

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.

Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.4/BA.5 in One Dose Groups.Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

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.

Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.4/BA.5 in Two Dose Group.Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

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.

Geometric Mean (GM) AUC of Antibody Against Wa-1 in One Dose Groups.Day 1 Pre-Booster Dose, Day 29, Day 91, Day 181, Day 271, Day 366

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.

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

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

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

Geometric Mean (GM) AUC of Antibody Against BA.1 in One Dose Groups.Day 1 Pre-Booster Dose, Day 29, Day 91, Day 181, Day 271, Day 366

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.

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

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

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

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

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

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

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

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

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

Geometric Mean (GM) of Pseudovirus Neutralization Against BA.2.12.1 in One Dose Groups.Day 1 Pre-Booster Dose, Day 15

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

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

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

Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.351 in One Dose Groups.Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

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.

Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.351 in Two Dose Group.Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

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.

Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.617.2 in One Dose Groups.Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

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.

Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.617.2 in Two Dose Group.Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

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.

Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.1 in One Dose Groups.Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

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.

Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.1 in Two Dose Group.Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

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.

Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.2.12.1 in One Dose Groups.Day 1 Pre-Booster Dose, Day 15

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.

Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.4/BA.5 in One Dose Groups.Day 1 Pre-Booster Dose, Day 15, Day 29, Day 91, Day 181, Day 271, Day 366

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.

Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.4/BA.5 in Two Dose Group.Day 1 Pre-Booster Dose, Day 15, Day 29, Day 57, Day 85, Day 147, Day 237, Day 327, Day 422

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.

Secondary Outcome Measures
NameTimeMethod
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.

Number of participants that experienced any AE during the course of the study that resulted in withdrawal from the study.

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.

Number of participants that experienced any AESI during the course of the study.

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.

Number of participants that experienced any MAAE during the course of the study. Medically Attended Adverse Events (MAAEs) are defined as a hospitalization \< 24 hours, emergency room visit or an otherwise unscheduled visit to or from medical personnel for any reason; and considered related or possibly related to study product

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.

Number of participants that experienced any NOCMC during the course of the study.

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.

Number of participants that experienced any SAEs during the course of the study. An AE or suspected adverse reaction is considered serious if, in the view of either the participating site PI or appropriate sub-investigator or the sponsor, it results in: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

Frequency of Systemic Solicited Reactogenicity Adverse Events (AEs)Day 1 through Day 8 for Arms 1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, and 17 and through 7 days post any vaccination for Arm 3.

Number of participants who experienced any systemic solicited AEs through 7 days post any vaccination. Systemic events include: fatigue, headache, myalgia, arthralgia, nausea, chills and fever.

Frequency of Local Solicited Reactogenicity Adverse Events (AEs)Day 1 through Day 8 for Arms 1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, and 17 and through 7 days post any vaccination for Arm 3.

Number of participants who experienced any local solicited AEs through 7 days post any vaccination. Local events include: Injection Site Pain, Injection site Erythema, and Injection site Edema/Induration.

Frequency of Any Unsolicited Adverse Events (AEs)Day 1 through Day 29 for Arms 1, 2, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, and 17 and 28 days post any vaccination for Arm 3.

Number of participants that experienced any Unsolicited AEs through 28 days post vaccination.

Trial Locations

Locations (22)

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

🇺🇸

San Diego, California, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

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

🇺🇸

Birmingham, Alabama, United States

Zuckerberg San Francisco General Hospital, UCSF Positive Health Program

🇺🇸

San Francisco, California, United States

George Washington University Medical Faculty Associates

🇺🇸

Washington, District of Columbia, United States

Howard University - Department of Medicine - Division of Infectious Disease

🇺🇸

Washington, District of Columbia, United States

Morehouse School of Medicine - Clinical Research Center

🇺🇸

Atlanta, Georgia, United States

Emory University School of Medicine

🇺🇸

Atlanta, Georgia, United States

The Hope Clinic of Emory University

🇺🇸

Decatur, Georgia, United States

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

🇺🇸

Chicago, Illinois, United States

University of Iowa Hospitals & Clinics - Department of Internal Medicine

🇺🇸

Iowa City, Iowa, United States

Tulane University Clinical Translational Unit

🇺🇸

New Orleans, Louisiana, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

Saint Louis University Center for Vaccine Development

🇺🇸

Saint Louis, Missouri, United States

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

🇺🇸

Saint Louis, Missouri, United States

NYU Grossman School, NYU Langone Vaccine Center, Long Island

🇺🇸

Mineola, New York, United States

NYU Langone Vaccine Center Research Clinic, Manhattan

🇺🇸

New York, New York, United States

University of Rochester Medical Center - Vaccine Research Unit

🇺🇸

Rochester, New York, United States

Duke Vaccine and Trials Unit

🇺🇸

Durham, North Carolina, United States

University of Texas Medical Branch

🇺🇸

League City, Texas, United States

Kaiser Permanente Washington Health Research Institute

🇺🇸

Seattle, Washington, United States

The University of Washington - Virology Research Clinic

🇺🇸

Seattle, Washington, United States

© Copyright 2025. All Rights Reserved by MedPath