Phase 2
N=1,270
COVID-19 Variant Immunologic Landscape Trial (COVAIL Trial)
COVID-19
Bottom Line
View on ClinicalTrials.gov: NCT05289037 ↗Enrolled (actual)
1,270
Serious AEs
2.4%
Results posted
Mar 2025
Primary outcome: Primary: Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against Wa-1 in One Dose Groups. — 4.57; 3.61; 3.78; 3.87 fold rise
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- AS03 (Drug); BNT162b2 (Biological); BNT162b2 (B.1.1.529) (Biological); BNT162b2 (B.1.351) (Biological); BNT162b2 bivalent (wildtype and Omicron BA.1) (Biological); BNT162b2 bivalent (wildtype and Omicron BA.4/BA.5) (Biological); CoV2 preS dTM [B.1.351] (Biological); CoV2 preS dTM/D614 (Biological); CoV2 preS dTM/D614+B.1.351 (Biological); mRNA-1273 (Biological); mRNA-1273.351 (Biological); mRNA-1273.529 (Biological); mRNA-1273.617.2 (Biological); Sodium Chloride, 0.9% (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Primary completion
- Nov 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against Wa-1 in One Dose Groups. |
4.57; 3.61; 3.78; 3.87; 3.67; 3.25 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against Wa-1 in Two Dose Group. |
4.09; 3.02; 4.85; 3.74; 2.68; 2.31 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against B.1.351 in One Dose Groups. |
4.66; 4.31; 4.50; 4.96; 4.28; 3.59 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against B.1.351 in Two Dose Group. |
5.30; 4.07; 6.61; 4.55; 3.44; 2.91 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against BA.1 in One Dose Groups. |
5.24; 4.95; 5.35; 6.19; 5.30; 3.89 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of AUC From Baseline Antibody Against BA.1 in Two Dose Group. |
5.96; 4.69; 7.99; 5.28; 3.47; 2.91 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against D614G in One Dose Groups. |
6.49; 5.41; 6.88; 4.98; 7.31; 4.27 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against D614G in Two Dose Group. |
5.35; 3.81; 3.33; 4.88; 2.97; 3.73 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.351 in One Dose Groups. |
9.47; 12.48; 11.51; 12.01; 11.23; 5.70 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.351 in Two Dose Group. |
13.31; 9.27; 7.10; 12.37; 5.98; 6.60 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.617.2 in One Dose Groups. |
7.22; 7.26; 8.18; 6.10; 7.89; 4.50 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against B.1.617.2 in Two Dose Group. |
6.72; 4.98; 4.15; 6.60; 3.32; 3.43 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.1 in One Dose Groups. |
10.10; 16.85; 16.34; 17.50; 15.32; 5.93 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.1 in Two Dose Group. |
17.18; 12.96; 9.08; 16.67; 10.48; 8.78 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.2.12.1 in One Dose Groups. |
10.84; 9.34; 11.84; 9.01; 8.65 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.4/BA.5 in One Dose Groups. |
12.31; 10.06; 16.19; 9.20; 12.25; 8.45 | — |
| PRIMARY Geometric Mean Fold Rise (GMFR) of Pseudovirus Neutralization From Baseline Antibody Against BA.4/BA.5 in Two Dose Group. |
40.80; 10.61; 8.51; 15.55; 9.05; 11.11 | — |
| PRIMARY Geometric Mean (GM) AUC of Antibody Against Wa-1 in One Dose Groups. |
160130.96; 207723.16; 202202.73; 196631.40; 212964.59; 235396.11 | — |
| PRIMARY Geometric Mean (GM) AUC of Antibody Against Wa-1 in Two Dose Group. |
170503.26; 606554.56; 494683.51; 762319.06; 582298.62; 447713.57 | — |
| PRIMARY Geometric Mean (GM) AUC of Antibody Against B.1.351 in One Dose Groups. |
93551.19; 129906.22; 116649.05; 115206.13; 128531.47; 135763.15 | — |
| PRIMARY Geometric Mean (GM) AUC of Antibody Against B.1.351 in Two Dose Group. |
99752.03; 467456.52; 383162.27; 601632.71; 440762.25; 339450.17 | — |
| PRIMARY Geometric Mean (GM) AUC of Antibody Against BA.1 in One Dose Groups. |
35858.62; 50667.27; 46101.27; 43880.60; 48636.02; 53148.74 | — |
| PRIMARY Geometric Mean (GM) AUC of Antibody Against BA.1 in Two Dose Group. |
39029.80; 232195.94; 184155.65; 303406.48; 206168.23; 132219.79 | — |
| PRIMARY Geometric Mean (GM) of Pseudovirus Neutralization Against D614G in One Dose Groups. |
3245.3; 3959.5; 3537.5; 3874.1; 3595.9; 4761.5 | — |
| PRIMARY Geometric Mean (GM) of Pseudovirus Neutralization Against D614G in Two Dose Group. |
3358.3; 17962.2; 12816.7; 11171.5; 16328.8; 9988.4 | — |
| PRIMARY Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.351 in One Dose Groups. |
810.8; 1069.4; 862.6; 933.8; 963.6; 1223.6 | — |
| PRIMARY Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.351 in Two Dose Group. |
847.0; 11275.7; 7800.2; 6008.9; 10285.2; 5061.1 | — |
| PRIMARY Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.617.2 in One Dose Groups. |
1602.4; 1842.0; 1783.4; 1898.6; 1771.4; 2261.3 | — |
| PRIMARY Geometric Mean (GM) of Pseudovirus Neutralization Against B.1.617.2 in Two Dose Group. |
1508.5; 10135.8; 7478.5; 6256.1; 9866.0; 5012.4 | — |
| PRIMARY Geometric Mean (GM) of Pseudovirus Neutralization Against BA.1 in One Dose Groups. |
264.4; 311.2; 278.1; 343.8; 348.4; 420.3 | — |
| PRIMARY Geometric Mean (GM) of Pseudovirus Neutralization Against BA.1 in Two Dose Group. |
249.7; 4289.3; 3235.4; 2322.2; 4111.6; 2616.7 | — |
| PRIMARY Geometric Mean (GM) of Pseudovirus Neutralization Against BA.2.12.1 in One Dose Groups. |
173.5; 209.1; 217.0; 352.9; 345.2; 1879.9 | — |
| PRIMARY Geometric Mean (GM) of Pseudovirus Neutralization Against BA.4/BA.5 in One Dose Groups. |
155.3; 170.8; 152.0; 195.4; 174.0; 206.8 | — |
| PRIMARY Geometric Mean (GM) of Pseudovirus Neutralization Against BA.4/BA.5 in Two Dose Group. |
132.1; 816.0; 1416.8; 1148.9; 2029.1; 1195.3 | — |
| PRIMARY Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.351 in One Dose Groups. |
0.25; 0.27; 0.24; 0.24; 0.27; 0.26 | — |
| PRIMARY Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.351 in Two Dose Group. |
0.25; 0.63; 0.61; 0.54; 0.63; 0.51 | — |
| PRIMARY Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.617.2 in One Dose Groups. |
0.49; 0.47; 0.50; 0.49; 0.49; 0.47 | — |
| PRIMARY Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against B.1.617.2 in Two Dose Group. |
0.45; 0.56; 0.58; 0.56; 0.60; 0.50 | — |
| PRIMARY Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.1 in One Dose Groups. |
0.08; 0.08; 0.08; 0.09; 0.10; 0.09 | — |
| PRIMARY Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.1 in Two Dose Group. |
0.07; 0.24; 0.25; 0.21; 0.25; 0.26 | — |
| PRIMARY Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.2.12.1 in One Dose Groups. |
0.07; 0.04; 0.05; 0.06; 0.07; 0.11 | — |
| PRIMARY Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.4/BA.5 in One Dose Groups. |
0.05; 0.04; 0.04; 0.05; 0.05; 0.04 | — |
| PRIMARY Geometric Mean Ratio (GMR) to D614G Variant of Pseudovirus Neutralization Against BA.4/BA.5 in Two Dose Group. |
0.04; 0.06; 0.11; 0.10; 0.12; 0.12 | — |
| SECONDARY Frequency of Any Adverse Events (AEs) Leading to Withdrawal From the Study. |
0; 0; 0; 0; 0; 1 | — |
| SECONDARY Frequency of Any Adverse Events of Special Interest (AESIs) |
3; 7; 7; 5; 3; 1 | — |
| SECONDARY Frequency of Any Medically Attended Adverse Events (MAAEs) |
2; 0; 2; 1; 0; 1 | — |
| SECONDARY Frequency of Any New Onset Chronic Medical Conditions (NOCMCs) |
2; 8; 4; 5; 3; 1 | — |
| SECONDARY Frequency of Any Serious Adverse Events (SAEs) |
4; 4; 7; 2; 3; 4 | — |
| SECONDARY Frequency of Systemic Solicited Reactogenicity Adverse Events (AEs) |
82; 88; 70; 80; 81; 80 | — |
| SECONDARY Frequency of Local Solicited Reactogenicity Adverse Events (AEs) |
93; 101; 77; 87; 82; 80 | — |
| SECONDARY Frequency of Any Unsolicited Adverse Events (AEs) |
26; 40; 39; 31; 35; 33 | — |
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.
Eligibility Criteria
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 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)
Data sourced from ClinicalTrials.gov (NCT05289037). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.