A Study to Evaluate VXA-CoV2-3.3 COVID-19 Vaccine Against Currently Approved/Authorized mRNA COVID-19 Injectable Booster Vaccine in Adults Previously Immunized Against COVID-19 Infection

NCT ID: NCT06672055

Last Updated: 2025-10-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

10400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-08

Study Completion Date

2026-11-30

Brief Summary

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The primary objective of the study is to determine the relative efficacy of the investigational oral severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine tablet VXA-CoV2-3.3 compared to a currently recommended vaccine for the prevention of symptomatic Coronavirus Disease 2019 (COVID-19).

In order to represent a more recently circulating SARS-CoV-2 variant, the main study endpoints will now evaluate the VXA-CoV2-3.3 (KP.2 strain) vaccine, and not the VXA-CoV2-3.1 (XBB.1.5 strain) vaccine.

Detailed Description

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Conditions

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SARS-CoV2 COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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VXA-CoV2-3.1 Safety Sentinel Cohort

Participants previously immunized against COVID-19 infection will be randomized to receive VXA-CoV2-3.1 (XBB.1.5 vaccine) tablet oral vaccine.

Group Type EXPERIMENTAL

VXA-CoV2-3.1

Intervention Type BIOLOGICAL

Tablets for oral use.

COMIRNATY® Safety Sentinel Cohort

Participants previously immunized against COVID-19 infection will be randomized to receive COMIRNATY® (variant matched vaccine 2023-2024 formula) injectable COVID-19 vaccine.

Group Type ACTIVE_COMPARATOR

COMIRNATY®

Intervention Type BIOLOGICAL

Intramuscular (IM) injection.

VXA-CoV2-3.3

If no dose-related toxicities are observed, and upon the recommendation of the Data and Safety Monitoring Board following review of Day 31 safety data in the initial safety cohorts (and possibly immunogenicity data), enrollment will continue with the remaining participants who will be randomized to receive a single dose of VXA-CoV2-3.3 (KP.2 vaccine).

Group Type EXPERIMENTAL

VXA-CoV2-3.3

Intervention Type BIOLOGICAL

Tablets for oral use.

COMIRNATY®

If no dose-related toxicities are observed, and upon the recommendation of the Data and Safety Monitoring Board following review of Day 31 safety data in the initial safety cohorts (and possibly immunogenicity data), enrollment will continue with the remaining participants who will be randomized to receive a single dose of 2024-2025 formula of COMIRNATY® mRNA COVID-19 injectable vaccine.

Group Type ACTIVE_COMPARATOR

COMIRNATY®

Intervention Type BIOLOGICAL

Intramuscular (IM) injection.

Interventions

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VXA-CoV2-3.1

Tablets for oral use.

Intervention Type BIOLOGICAL

COMIRNATY®

Intramuscular (IM) injection.

Intervention Type BIOLOGICAL

VXA-CoV2-3.3

Tablets for oral use.

Intervention Type BIOLOGICAL

Other Intervention Names

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Pfizer-BioNTech mRNA Vaccine

Eligibility Criteria

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Inclusion Criteria

1. Adults 18 years of age and above, at time of screening.
2. Completed primary approved/authorized COVID-19 vaccination series with ≥ 2 mRNA vaccine doses.
3. Last COVID-19 vaccine received ≥6 months prior to study vaccination.
4. Male and female participants of childbearing potential must agree to consistently use a highly effective method of contraception from at least 30 days prior to enrollment and through 3 months after the study vaccination.
5. Male participants must refrain from sperm donation from the day of study vaccination through the end of the study. Female participants must refrain from egg donation at least 30 days prior to study vaccination through the end of the study.
6. Is medically stable, as determined by the site investigator (based on review of health status, vital signs, medical history, and physical examination) with screening lab values within normal limits or abnormalities assessed as not clinically significant. Screening platelet count must be \>140,000/μL.
7. Agree to not participate in any other SARS-CoV-2 infection prevention trial (vaccine, drug, biologic, PrEP) during participation in the study.
8. Willing and able to provide informed consent prior to initiation of study procedures.
9. Available for all study visits, willing to participate in all study procedures, and not planning to relocate from the area for the duration of the study.
10. Negative rapid molecular Covid test at the screening visit and on Day 1 prior to vaccine dosing.

Exclusion Criteria

1. Participant has an acute illness as defined by any of the following (note: assessment may be repeated once during screening period) as determined by the site investigator, within 72 hours prior to vaccination as follows:

1. An acute illness that is nearly resolved, with only minor residual symptoms remaining, is allowable if, in the opinion of the site investigator, the residual symptoms will not interfere with the ability of study staff to assess safety parameters as required by the protocol.
2. Presence of a fever ≥ 38.0°C (100.4°F) measured orally at baseline, on Day 1 prior to vaccination.
3. Receipt of antipyretic/analgesic medications within 24 hours prior to vaccine administration.
2. Participant has had a positive COVID test within 90 days prior to screening.
3. Current or planned participation in any other interventional clinical trial.
4. Participation in research involving any investigational product within 45 days prior to study vaccination.
5. Receipt of any approved or authorized products intended to prevent SARS-CoV2 infection within 6 months prior to study vaccination.
6. Receipt or donation of blood products or immunoglobulins within 60 days prior to enrollment or planned administration during the study.
7. Received influenza vaccination within 14 days prior to study vaccination, or any other vaccine within 30 days prior to study vaccination.
8. Any autoimmune or immunodeficiency disease/condition (including and not limited to untreated or advanced HIV infection with CD4 counts \<200 cells/mm\^3, history of AIDS defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV, severe combined immunodeficiency (SCID), hypogammaglobulinemia, asplenia or functional asplenia).
9. Unstable medical or psychiatric illness (acute or chronic illness) requiring significant medical monitoring and intervention during the 90 days prior to enrollment. Note: diabetes mellitus (Types 1 \& 2) are not excluded if assessed by the principal investigator (PI) as well-controlled.
10. Administration of immunosuppressants, systemic glucocorticoids, or other immune-modifying drugs within the following timeframes:

1. B-cell therapies within the 6 months prior to first study vaccination
2. Prednisone, ≥20 mg for more than 2 weeks, within the 30 days prior to study vaccination
3. Other medications in this category, including but not limited to high-dose inhaled corticosteroids (\>800 mcg/day of beclomethasone dipropionate or equivalent); antimetabolites; transplant immunosuppressive agents; alkylating agents; cell-depleting agents; or cancer chemotherapeutics, within the 90 days prior to study vaccination.
4. Any medication for any period of time that, in the opinion of the site investigator, could impede immune response to vaccination.
5. Use of any dose montelukast OR inhaled, intranasal, intra-articular, or systemic corticosteroids within 2 weeks prior to study vaccination.
6. Planned use of any of the above medications during the study.
7. Concomitant allergen immunotherapy (AIT) will be allowed only if the participant is stable in the maintenance phase of AIT. Maintenance AIT should not be dosed for at least 7 days before and 7 days after study vaccine dosing, and the PI must document the treating allergist's approval.
11. Known contraindication to IM injection or blood draws (e.g. bleeding diathesis, acquired coagulopathy, significant bleeding or bruising) or to oral route of administration (unable to swallow tablets).
12. Any known allergies to components contained in the investigational product or comparator or latex allergy (including polyethylene glycol \[PEG\] allergies) and/or history of serious reactions to vaccination such as anaphylaxis, respiratory problems, hives, or abdominal pain.
13. Women who are pregnant (pregnancy tests will be performed at screening and prior to dosing), breastfeeding, or who plan to become pregnant during the study.
14. History of irritable bowel disease or other inflammatory digestive or gastrointestinal condition that could affect the distribution/safety evaluation of an orally administered vaccine targeting the mucosa of the small intestine. Such conditions may include but are not limited to:

1. Any history of:

* GI malignancy
* malabsorption
* pancreatobiliary disorders
* inflammatory bowel disease
* irritable bowel disease
* hiatal hernia
* surgical resection
2. History of diagnosis or treatment in past 5 years of:

* esophageal or gastric motility disorder
* gastroesophageal reflux disorder
* peptic ulcer
* cholecystectomy.
15. Use of antibiotics, proton pump inhibitors, H2 blockers, or antacids within 7 days prior to study drug administration or planned use from dosing through Day 31.
16. Use of drugs known to affect gastrointestinal motility including glucagon-like peptide 1 (GLP-1) receptor agonists including tirzepatide (Mounjaro) and semaglutide (Wegovy, Ozempic) within 30 days prior to drug administration.
17. Daily use of nonsteroidal anti-inflammatory drugs within 7 days prior to study drug administration or planned use during the study.
18. Personal or familial history of hypercoagulable states to include personal past history of deep vein thrombosis (DVT).
19. Personal history of myocarditis or pericarditis.
20. Positive Hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody at the screening visit.
21. History of drug, alcohol, or chemical abuse within 1 year of screening.
22. Positive urine drug screen for drugs of abuse at screening (except for occasional marijuana use). Concurrent or planned use of marijuana from dosing through Day 31 is prohibited. Positive urine drug screen (UDS) at screening due to prescribed stimulants will be reviewed on a case by case basis.
23. Cancer, or treatment for cancer, within the past 3 years (excluding fully treated and resolved basal cell carcinoma or squamous cell carcinoma).
24. History of any form of angioedema.
25. History of GI bleeding including hematochezia (blood in stool) or melena (black stool) of unknown etiology or that has not been evaluated.
26. Any history or conditions that may lead to a higher risk of clotting events and/or thrombocytopenia, including:

1. Familial coagulopathy or personal history of bleeding disorder or thrombosis
2. History of heparin-related thrombotic events, and/or receiving heparin treatments
3. History of autoimmune or inflammatory disease
4. Presence of any of the following conditions known to increase the risk of thrombosis within 6 months prior to screening:

* Recent surgery other than fully healed cesarean delivery or excision/ biopsy of cutaneous lesions
* Immobility (confined to bed or wheelchair for 3 or more successive days)
* Head trauma with loss of consciousness or documented brain injury
* Receipt of anticoagulants for prophylaxis of thrombosis
* Recent clinically significant infection including hospitalization for COVID-19 related illness.
27. Any other condition that, in the opinion of the investigator, would pose a health risk to the participant if enrolled or could interfere with evaluation of the investigational product or interpretation of study results.
28. Study team member or first-degree relative of any study team member (inclusive of sponsor and site personnel involved in the study).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vaxart

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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James Cummings, MD

Role: STUDY_DIRECTOR

Vaxart, Inc.

Locations

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Pinnacle Research Group

Anniston, Alabama, United States

Site Status

Core Clinical Trials - Central Alabama Research LLC

Birmingham, Alabama, United States

Site Status

Coastal Clinical Research

Mobile, Alabama, United States

Site Status

Avacare - Lenzmeier Family Medicine

Glendale, Arizona, United States

Site Status

Desert Clinical Research

Mesa, Arizona, United States

Site Status

Velocity Clinical Research - MedPharmics - Phoenix

Phoenix, Arizona, United States

Site Status

Foothills Research Center

Phoenix, Arizona, United States

Site Status

Avacare (CCT) - Fiel Family & Sports Medicine

Tempe, Arizona, United States

Site Status

Baptist Health Center for Clinical Research - Little Rock

Little Rock, Arkansas, United States

Site Status

Elligo Health Research (BTC/ClinEdge) - Core Healthcare Group

Cerritos, California, United States

Site Status

Velocity Clinical Research - Chula Vista (eStudySite - Chula Vista)

Chula Vista, California, United States

Site Status

Avacare - Benchmark Research - SOCAL-Colton

Colton, California, United States

Site Status

Altasciences Los Angeles (Formerly WCCT Global)

Cypress, California, United States

Site Status

Ark Clinical Research - Fountain Valley, CA

Fountain Valley, California, United States

Site Status

Velocity Clinical Research - San Diego (eStudySite - La Mesa)

La Mesa, California, United States

Site Status

Ark Clinical Research - Long Beach, CA

Long Beach, California, United States

Site Status

Velocity Clinical Research (National Research Institute) - Panorama City

Los Angeles, California, United States

Site Status

Northern California Research

Sacramento, California, United States

Site Status

Avacare - Benchmark Research - Sacramento

Sacramento, California, United States

Site Status

Velocity Clinical Research - Gardena

Santa Ana, California, United States

Site Status

Elite Research Network (ERN) - Legacy Clinical Trials

Colorado Springs, Colorado, United States

Site Status

Tekton Research - Fort Collins

Fort Collins, Colorado, United States

Site Status

Avacare - Critical Care, Pulmonary and Sleep Associates

Lakewood, Colorado, United States

Site Status

Tekton Research - Colorado - Longmont

Longmont, Colorado, United States

Site Status

Paradigm Clinical Research - Wheat Ridge

Wheat Ridge, Colorado, United States

Site Status

Stamford Therapeutics Consortium

Stamford, Connecticut, United States

Site Status

Chase Medical Research

Waterbury, Connecticut, United States

Site Status

Velocity Clinical Research - Washington DC

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

Site Status

AMR - Miami (Clinical Research of South Florida)

Coral Gables, Florida, United States

Site Status

Universal Axon Clinical Research

Doral, Florida, United States

Site Status

Velocity Clinical Research - New Smyrna Beach

Edgewater, Florida, United States

Site Status

Fleming Island Center For Clinical Research

Fleming Island, Florida, United States

Site Status

AMR - Fort Myers - Clinical Physiology Associates

Fort Myers, Florida, United States

Site Status

Velocity Clinical Research - Hallandale Beach (MD Clinical)

Hallandale, Florida, United States

Site Status

ENCORE - Nature Coast Clinical Research Inverness

Inverness, Florida, United States

Site Status

ENCORE - Westside Center for Clinical Research

Jacksonville, Florida, United States

Site Status

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Site Status

Headlands Research - JEM Research - Lake Worth

Lake Worth, Florida, United States

Site Status

Accel Research Sites - Lakeland

Lakeland, Florida, United States

Site Status

Accel Research Sites (ARS) - St. Petersburg - Largo

Largo, Florida, United States

Site Status

Accel Research Sites - Maitland

Maitland, Florida, United States

Site Status

K2 Medical Research - Maitland

Maitland, Florida, United States

Site Status

SRA Trials LLC - Miami Clinical Trials at Suncoast Research Associates

Miami, Florida, United States

Site Status

Atlas Clinical Research - Suncoast Clinical Research - Pasco County

New Port Richey, Florida, United States

Site Status

Biscayne Clinical Research

North Miami Beach, Florida, United States

Site Status

K2 Medical Research - South Orlando

Orlando, Florida, United States

Site Status

Boca Raton Clinical Research (BRCR) Global - Weston

Plantation, Florida, United States

Site Status

ENCORE - St. Johns Center for Clinical Research

Saint Augustine, Florida, United States

Site Status

IMA Clinical Research - St. Petersburg

St. Petersburg, Florida, United States

Site Status

hyperCORE - Centricity Research Columbus

Columbus, Georgia, United States

Site Status

Javara Research - Privia Medical Group Georgia

Fayetteville, Georgia, United States

Site Status

Privia Health - SouthCoast Health

Fayetteville, Georgia, United States

Site Status

Avacare (CCT) - Lifeline Primary Care

Lilburn, Georgia, United States

Site Status

hyperCORE - Centricity Research (IACT Health) - Rincon

Rincon, Georgia, United States

Site Status

Velocity Clinical Research - Savannah

Savannah, Georgia, United States

Site Status

Velocity Clinical Research - Boise (Meridian)

Meridian, Idaho, United States

Site Status

IMA Clinical Research - Chicago

Chicago, Illinois, United States

Site Status

Accellacare - Duly Health and Care

Lombard, Illinois, United States

Site Status

Velocity Clinical Research - Valparaiso (Buynak Clinical Research)

Valparaiso, Indiana, United States

Site Status

Accellacare - McFarland Clinic

Ames, Iowa, United States

Site Status

Velocity (Meridian) Clinical Research - Sioux City

Sioux City, Iowa, United States

Site Status

AMR - El Dorado - Heartland Research Associates

El Dorado, Kansas, United States

Site Status

Johnson County Clin-Trials

Lenexa, Kansas, United States

Site Status

AMR - Newton (Heartland Research Associates)

Newton, Kansas, United States

Site Status

AMR - Wichita West - Heartland Research Associates

Wichita, Kansas, United States

Site Status

AMR - Wichita East - Heartland Research Associates

Wichita, Kansas, United States

Site Status

AMR - Lexington (Central Kentucky Research Associates)

Lexington, Kentucky, United States

Site Status

Velocity (Meridian) Clinical Research - Baton Rouge

Baton Rouge, Louisiana, United States

Site Status

Avacare - Benchmark Research - New Orleans-North Shore

Covington, Louisiana, United States

Site Status

Velocity Clinical Research - MedPharmics - Covington

Covington, Louisiana, United States

Site Status

Boca Raton Clinical Research (BRCR) Global USA - New Orleans

Gretna, Louisiana, United States

Site Status

Velocity Clinical Research - MedPharmics - Lafayette

Lafayette, Louisiana, United States

Site Status

Avacare - Benchmark Research - Metairie

Metairie, Louisiana, United States

Site Status

AMR - New Orleans - Center for Clinical Research

New Orleans, Louisiana, United States

Site Status

Javara Research - Privia Medical Group Mid-Atlantic - Annapolis

Annapolis, Maryland, United States

Site Status

Pharmaron

Baltimore, Maryland, United States

Site Status

Avacare (CCT) - Advanced Primary and Geriatric Care

Rockville, Maryland, United States

Site Status

Velocity (Meridian) Clinical Research - Rockville

Rockville, Maryland, United States

Site Status

Javara Research - Mankato Clinic

Mankato, Minnesota, United States

Site Status

Velocity Clinical Research - MedPharmics - Gulfport

Gulfport, Mississippi, United States

Site Status

Avacare (CCT) - Clay Platte Family Medicine Clinic

Kansas City, Missouri, United States

Site Status

Avacare (CCT) - Skyline Medical Center

Elkhorn, Nebraska, United States

Site Status

Velocity (Meridian) Clinical Research - Grand Island

Grand Island, Nebraska, United States

Site Status

Be Well Clinical Studies - Nebraska

Lincoln, Nebraska, United States

Site Status

Velocity (Meridian) Clinical Research - Omaha

Omaha, Nebraska, United States

Site Status

hyperCORE - ActivMed Practices and Research - Portsmouth

Portsmouth, New Hampshire, United States

Site Status

DM Clinical Research - Jersey City

Jersey City, New Jersey, United States

Site Status

Velocity Clinical Research - Alburquerque

Albuquerque, New Mexico, United States

Site Status

AXCES Research & Health - Santa Fe

Santa Fe, New Mexico, United States

Site Status

IMA Clinical Research - Albany, Suite 202

Albany, New York, United States

Site Status

Velocity Clinical Research - Syracuse

East Syracuse, New York, United States

Site Status

IMA Clinical Research - Manhattan

New York, New York, United States

Site Status

Atlas Clinical Research - Rochester Clinical Research

Rochester, New York, United States

Site Status

Cary Medical Group

Cary, North Carolina, United States

Site Status

Velocity Clinical Research - Durham

Durham, North Carolina, United States

Site Status

Accellacare - Hickory

Hickory, North Carolina, United States

Site Status

Accellacare - Raleigh

Raleigh, North Carolina, United States

Site Status

Accellacare - Rocky Mount

Rocky Mount, North Carolina, United States

Site Status

Accellacare - Salisbury

Salisbury, North Carolina, United States

Site Status

Accellacare - Piedmont Healthcare

Statesville, North Carolina, United States

Site Status

Accellacare - Tradd Court

Wilmington, North Carolina, United States

Site Status

Accellacare - Winston-Salem

Winston-Salem, North Carolina, United States

Site Status

Atrium Health Wake Forest Baptist - Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status

Velocity Clinical Research - Cleveland (Rapid Medical Research)

Beachwood, Ohio, United States

Site Status

CTI Clinical Research Center

Cincinnati, Ohio, United States

Site Status

Velocity Clinical Research - Cincinnati (New Horizons Clinical Research - Blue Ash)

Cincinnati, Ohio, United States

Site Status

Tekton Research - Oklahoma - Magnolia Court

Moore, Oklahoma, United States

Site Status

Tekton Research - Delaware Pointe

Tulsa, Oklahoma, United States

Site Status

Tekton Research - Oklahoma - Primary Health Partners

Yukon, Oklahoma, United States

Site Status

Velocity Clinical Research - Grants Pass

Grants Pass, Oregon, United States

Site Status

Avacare (CCT) - Hatboro Medical Associates

Hatboro, Pennsylvania, United States

Site Status

Atlas Clinical Research - Suburban Research Associates - Media Office

Media, Pennsylvania, United States

Site Status

Velocity Clinical Research - Providence (East Greenwich)

East Greenwich, Rhode Island, United States

Site Status

Velocity Clinical Research - Anderson

Anderson, South Carolina, United States

Site Status

Velocity Clinical Research - Charleston

Charleston, South Carolina, United States

Site Status

Velocity Clinical Research - Columbia (VitaLink)

Columbia, South Carolina, United States

Site Status

Accellacare - Charleston

Mt. Pleasant, South Carolina, United States

Site Status

Trial Management Associates - Myrtle Beach

Myrtle Beach, South Carolina, United States

Site Status

hyperCORE International - Coastal Carolina Research Center

North Charleston, South Carolina, United States

Site Status

Velocity Clinical Research - Union (Vitalink)

Union, South Carolina, United States

Site Status

Accellacare - PMG Research of Bristol

Bristol, Tennessee, United States

Site Status

Alliance for Multispecialty Research (AMR) - Corporate

Knoxville, Tennessee, United States

Site Status

Accellacare of Knoxville

Knoxville, Tennessee, United States

Site Status

Velocity Clinical Research - Abilene

Abilene, Texas, United States

Site Status

IMA Clinical Research - Austin

Austin, Texas, United States

Site Status

Tekton Research - Austin

Austin, Texas, United States

Site Status

Orion Clinical Research

Austin, Texas, United States

Site Status

Velocity Clinical Research - Austin

Austin, Texas, United States

Site Status

Tekton Research - Beaumont

Beaumont, Texas, United States

Site Status

PanAmerican Clinical Research - Brownsville, Levee Street

Brownsville, Texas, United States

Site Status

Cedar Health Research - Arlington/Euless

Euless, Texas, United States

Site Status

EmVenio Research - Fort Worth, TX

Fort Worth, Texas, United States

Site Status

Avacare - Benchmark Research Fort Worth

Fort Worth, Texas, United States

Site Status

DM Clinical Research - CyFair Clinical Research Center

Houston, Texas, United States

Site Status

Tekton Research - Fredericksburg Road

San Antonio, Texas, United States

Site Status

DM Clinical Research - Tomball - Multiple Specialties

Tomball, Texas, United States

Site Status

Velocity Clinical Research - Waco (formerly: Impact Research Institute)

Waco, Texas, United States

Site Status

Avacare (CCT) - Ogden Clinic - Grand View

Roy, Utah, United States

Site Status

Avacare (CCT) - Olympus Family Medicine

Salt Lake City, Utah, United States

Site Status

South Ogden Family Medicine

South Ogden, Utah, United States

Site Status

Health Research of Hampton Roads

Newport News, Virginia, United States

Site Status

AMR - Norfolk (Clinical Research Associates of Tidewater)

Norfolk, Virginia, United States

Site Status

Centricity Research (IACT Health) - Suffolk Primary Care

Suffolk, Virginia, United States

Site Status

Velocity Clinical Research - Medford

Spokane, Washington, United States

Site Status

Velocity Clinical Research - Spokane

Spokane, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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VXA-COV-202

Identifier Type: -

Identifier Source: org_study_id

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