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Completed

NCT Number: NCT05289037

COVID-19 Variant Immunologic Landscape Trial (COVAIL Trial)

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.

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Key information

Conditions

COVID-19 Coronaviridae Infections Coronavirus Infections Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Alabama at Birmingham School of Medicine - Alabama Vaccine Research Clinic, Birmingham, Alabama, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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.

Exclusion criteria

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).

Note: Topical medications are allowed.

  • Received immunoglobulin or blood-derived products, within 3 months prior any study vaccine dose.
  • Received chemotherapy, immunotherapy or radiation therapy within 6 months prior to any study vaccine dose.
  • Study personnel or an immediate family member or household member of study personnel.
  • 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.

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

Treatment and study plan

AS03

Drug

AS03 oil-in-water emulsion adjuvant.

BNT162b2

Biological

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

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.

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.

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.

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.

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.

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.

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

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).

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.

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.

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.

Sodium Chloride, 0.9%

Other

0.9% Sodium Chloride Injection

Primary outcomes

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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

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

    Time frame: 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

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

    Time frame: 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

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

    Time frame: 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

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: Day 1 Pre-Booster Dose, Day 15

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

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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 outcomes

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

    Time frame: 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.

  2. Frequency of Any Adverse Events of Special Interest (AESIs)

    Time frame: 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.

  3. Frequency of Any Medically Attended Adverse Events (MAAEs)

    Time frame: 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

  4. Frequency of Any New Onset Chronic Medical Conditions (NOCMCs)

    Time frame: 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.

  5. Frequency of Any Serious Adverse Events (SAEs)

    Time frame: 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.

  6. Frequency of Systemic Solicited Reactogenicity Adverse Events (AEs)

    Time frame: 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.

  7. Frequency of Local Solicited Reactogenicity Adverse Events (AEs)

    Time frame: 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.

  8. Frequency of Any Unsolicited Adverse Events (AEs)

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Nih

Registry information

Official study title

Phase 2 Clinical Trial to Optimize Immune Coverage of SARS-CoV-2 Existing and Emerging Variants

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Mar 21, 2022
Registry last updated
Oct 20, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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