A Study to Learn About New COVID-19 RNA Vaccine Candidates in COVID-19 Vaccine-Experienced Healthy Individuals

NCT ID: NCT05472038

Last Updated: 2025-10-01

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

1453 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-26

Study Completion Date

2024-03-26

Brief Summary

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The purpose of this clinical trial is to learn about the safety, tolerability and immunogenicity of BNT162b RNA-based SARS-CoV-2 vaccine candidates in adults to prevent COVID-19.

For all cohorts (groups of participants), this study is seeking participants who are healthy (who may have preexisting disease if it is stable); All participants will receive a single dose of the study vaccine at the first study clinic and will return to the study clinic at least 4 more times. At each clinic visit, a blood sample will be taken. The study is about 6 months long for each participant. The vaccine candidates in this study are investigational but are very similar to BNT162b2 (Comirnaty), a COVID-19 RNA vaccine approved for use in the US and in many countries.

For Cohort 1, this study included participants who were:

* 18 through 55 years of age
* have received 1 booster dose of a US-authorized COVID-19 vaccine, with the last dose being 90 or more days before Visit 1 of this study.

All participants in Cohort 1 will receive 1 of the 2 study vaccines at a 30 microgram dose: BNT162b5 Bivalent (WT/OMI BA.2) or BNT162b2 Bivalent (WT/OMI BA.1).

For Cohort 2, this study included participants who were:

* 12 years of age and older
* have received 3 prior doses of 30 micrograms BNT162b2, with the last dose being 150 to 365 days before Visit 1 of this study.

Participants 12 through 17 years of age will receive BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 micrograms.

Participants 18 years and older will receive BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at either a 30 microgram or a 60 microgram dose.

For Cohort 3, this study included participants who were:

* 18 years of age and older
* have received 3 prior doses of 30 micrograms BNT162b2, with the last dose being 150 to 365 days before Visit 1 of this study.
* Participants will receive BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 micrograms.

For Cohort 4, this study is seeking participants who are:

* 18 through 55 years of age
* have received 3 or 4 prior doses of a US-authorized mRNA COVID-19 vaccine (and dose level), with the last dose being a US-authorized BA.4/BA.5-adapted bivalent vaccine and dose level at least 150 days before Visit 1 of this study.

All participants in Cohort 4 will receive 1 of the 5 study vaccines at a 30 microgram dose: BNT162b2 Bivalent (Original/ OMI BA.4/BA.5), BNT162b5 Bivalent (Original/OMI BA.4/BA.5), BNT162b6 Bivalent (Original/OMI BA.4/BA.5), BNT162b7 Bivalent (Original/OMI BA.4/BA.5) or BNT162b7 Monovalent (OMI BA.4/BA.5).

Detailed Description

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Conditions

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SARS-CoV-2 Infection COVID-19

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Phase 1/2/3, randomized, active-controlled, parallel group study.
Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Cohort 1 and Cohort 2 (18 years and older): Observer-blind Cohort 2 (12-17 years) and Cohort 3: Open-label Cohort 4: Observer-blind

Study Groups

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Cohort 1: BNT162b5 Bivalent (WT/OMI BA.2)

Participants will receive 30 µg of BNT162b5 Bivalent (WT/OMI BA.2) at Visit 1.

Group Type EXPERIMENTAL

BNT162b5 Bivalent (WT/OMI BA.2)

Intervention Type BIOLOGICAL

BNT162b5 Wild Type and BNT162b5 OMICRON \[B.1.1.529 sublineage BA.2\]

Cohort 1: BNT162b2 Bivalent (WT/OMI BA.1)

Participants will receive 30 µg of BNT162b2 Bivalent (WT/OMI BA.1) at Visit 1.

Group Type EXPERIMENTAL

BNT162b2 Bivalent (WT/OMI BA.1)

Intervention Type BIOLOGICAL

BNT162b2 Wild Type and BNT162b2 OMICRON \[B.1.1.529 sublineage BA.1\]

Cohort 2 -Group 1: 12-17 years; 30 µg

Participants 12-17 years old will receive 30 µg of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at Visit 1.

Group Type EXPERIMENTAL

BNT162b2 Bivalent (WT/OMI BA.4/BA.5)

Intervention Type BIOLOGICAL

BNT162b2 Wild Type and BNT162b2 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Cohort 2 - Group 2: 18-55 years; 30 µg

Participants 18-55 years old will receive 30 µg of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at Visit 1.

Group Type EXPERIMENTAL

BNT162b2 Bivalent (WT/OMI BA.4/BA.5)

Intervention Type BIOLOGICAL

BNT162b2 Wild Type and BNT162b2 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Cohort 2 - Group 3: 18-55 years; 60 µg

Participants 18-55 years old will receive 60 µg of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at Visit 1.

Group Type EXPERIMENTAL

BNT162b2 Bivalent (WT/OMI BA.4/BA.5)

Intervention Type BIOLOGICAL

BNT162b2 Wild Type and BNT162b2 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Cohort 2 - Group 4: >55 years; 30 µg

Participants over 55 years old will receive 30 µg of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at Visit 1.

Group Type EXPERIMENTAL

BNT162b2 Bivalent (WT/OMI BA.4/BA.5)

Intervention Type BIOLOGICAL

BNT162b2 Wild Type and BNT162b2 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Cohort 2 - Group 5: >55 years; 60 µg

Participants over 55 years old will receive 60 µg of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at Visit 1.

Group Type EXPERIMENTAL

BNT162b2 Bivalent (WT/OMI BA.4/BA.5)

Intervention Type BIOLOGICAL

BNT162b2 Wild Type and BNT162b2 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Cohort 3 - Group 1: 18-55 years; 30 µg

Participants will receive BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg at Visit 1.

Group Type EXPERIMENTAL

BNT162b2 Bivalent (WT/OMI BA.4/BA.5)

Intervention Type BIOLOGICAL

BNT162b2 Wild Type and BNT162b2 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Cohort 3 - Group 2: >55 years; 30 µg

Participants will receive BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg at Visit 1.

Group Type EXPERIMENTAL

BNT162b2 Bivalent (WT/OMI BA.4/BA.5)

Intervention Type BIOLOGICAL

BNT162b2 Wild Type and BNT162b2 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Cohort 4: BNT162b2 Bivalent (Original/OMI BA.4/BA.5)

Participants will receive 30 µg of BNT162b2 Bivalent (Original/OMI BA.4/BA.5) at Visit 1

Group Type ACTIVE_COMPARATOR

BNT162b2 Bivalent (WT/OMI BA.4/BA.5)

Intervention Type BIOLOGICAL

BNT162b2 Wild Type and BNT162b2 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Cohort 4: BNT162b5 Bivalent (Original/OMI BA.4/BA.5)

Participants will receive 30 µg of BNT162b5 Bivalent (Original/OMI BA.4/BA.5) at Visit 1

Group Type EXPERIMENTAL

BNT162b5 Bivalent (Original/OMI BA.4/BA.5)

Intervention Type BIOLOGICAL

BNT162b5 Wild Type and BNT162b5 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Cohort 4: BNT162b6 Bivalent (Original/OMI BA.4/BA.5)

Participants will receive 30 µg of BNT162b6 Bivalent (Original/OMI BA.4/BA.5) at Visit 1

Group Type EXPERIMENTAL

BNT162b6 Bivalent (Original/OMI BA.4/BA.5)

Intervention Type BIOLOGICAL

BNT162b6 Wild Type and BNT162b6 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Cohort 4: BNT162b7 Bivalent (Original/OMI BA.4/BA.5)

Participants will receive 30 µg of BNT162b7 Bivalent (Original/OMI BA.4/BA.5) at Visit 1

Group Type EXPERIMENTAL

BNT162b7 Bivalent (Original/OMI BA.4/BA.5)

Intervention Type BIOLOGICAL

BNT162b7 Wild Type and BNT162b7 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Cohort 4: BNT162b7 Monovalent (OMI BA.4/BA.5)

Participants will receive 30 µg of BNT162b7 Monovalent (OMI BA.4/BA.5) at Visit 1

Group Type EXPERIMENTAL

BNT162b7 Monovalent (OMI BA.4/BA.5)

Intervention Type BIOLOGICAL

BNT162b7 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Interventions

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BNT162b5 Bivalent (WT/OMI BA.2)

BNT162b5 Wild Type and BNT162b5 OMICRON \[B.1.1.529 sublineage BA.2\]

Intervention Type BIOLOGICAL

BNT162b2 Bivalent (WT/OMI BA.1)

BNT162b2 Wild Type and BNT162b2 OMICRON \[B.1.1.529 sublineage BA.1\]

Intervention Type BIOLOGICAL

BNT162b2 Bivalent (WT/OMI BA.4/BA.5)

BNT162b2 Wild Type and BNT162b2 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Intervention Type BIOLOGICAL

BNT162b5 Bivalent (Original/OMI BA.4/BA.5)

BNT162b5 Wild Type and BNT162b5 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Intervention Type BIOLOGICAL

BNT162b6 Bivalent (Original/OMI BA.4/BA.5)

BNT162b6 Wild Type and BNT162b6 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Intervention Type BIOLOGICAL

BNT162b7 Bivalent (Original/OMI BA.4/BA.5)

BNT162b7 Wild Type and BNT162b7 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Intervention Type BIOLOGICAL

BNT162b7 Monovalent (OMI BA.4/BA.5)

BNT162b7 OMICRON \[B.1.1.529 sublineage BA.4/BA.5\]

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Age:

* Cohort 1: 18 through 55 years of age.
* Cohort 2: 12 years of age and older.
* Cohort 3: 18 years of age and older.
* Cohort 4: 18 through 55 years of age.
2. Willing and able to comply with all scheduled visits/contacts, study procedures and lifestyle considerations.
3. Healthy participants (stable pre-existing disease permitted).
4. Capable of giving signed informed consent.
5. Prior COVID-19 vaccination history:

Cohort 1:

\- Received of 1 booster dose of a US-authorized COVID-19 vaccine, with the dose being 90 or more days before first study visit. Documented receipt of all prior COVID-19 vaccines is required.

Cohorts 2 and 3:

\- Received 3 prior doses of 30 micrograms BNT162b2, with last dose being 150 to 365 days before first study visit. Documented receipt of all prior COVID-19 vaccines is required.

Cohort 4:

\- Received 3 or 4 prior doses of a US-authorized mRNA COVID-19 vaccine (and dose level), with the last dose being a US-authorized Omicron BA.4/BA.5-adapted vaccine and dose level at least 150 days before first study visit. Documented receipt of all prior COVID-19 vaccines is required.

Exclusion Criteria

1. History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study vaccines.
2. Known or suspected immunodeficiency.
3. Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
4. Women who are pregnant or breastfeeding.
5. Other medical or psychiatric condition, or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
6. Immunosuppressants/radiotherapy:

Cohorts 1 and 2: Receipt of chronic systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days before study vaccination through end of study.

Cohorts 3 and 4: Receipt of chronic systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease), or radiotherapy, within 60 days before enrollment or planned receipt through conclusion of the study.
7. Blood/plasma products, immunoglobulin, or monoclonal antibodies:

Cohorts 1, 2, 3: Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study vaccination or planned receipt throughout the study.

Cohort 4: Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies used for treatment/prevention of COVID-19 or those considered immunosuppressive, from 60 days before study vaccination or planned receipt throughout the study.
8. Other study participation:

Cohorts 1 and 2: Participation in other studies involving a study intervention within 28 days before randomization. Anticipated participation in other studies within 28 days after receipt of study intervention in this study.

Cohorts 3 and 4: Participation in other studies involving receipt of a study intervention within 28 days before randomization. Anticipated participation in other studies involving a study intervention from randomization through the end of this study.
9. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
10. Cohort 4 only: History of myocarditis or pericarditis
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

BioNTech SE

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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Anaheim Clinical Trials, LLC

Anaheim, California, United States

Site Status

California Research Foundation

San Diego, California, United States

Site Status

Bayview Research Group, LLC

Valley Village, California, United States

Site Status

Diablo Clinical Research, Inc.

Walnut Creek, California, United States

Site Status

Clinical Research Consulting

Milford, Connecticut, United States

Site Status

Research Centers of America ( Hollywood )

Hollywood, Florida, United States

Site Status

Clinical Neuroscience Solutions, Inc. dba CNS Healthcare

Jacksonville, Florida, United States

Site Status

Acevedo Clinical Research Associates

Miami, Florida, United States

Site Status

Clinical Research Atlanta

Stockbridge, Georgia, United States

Site Status

East-West Medical Research Institute

Honolulu, Hawaii, United States

Site Status

Kentucky Pediatric/ Adult Research

Bardstown, Kentucky, United States

Site Status

Clinical Research Professionals

Chesterfield, Missouri, United States

Site Status

Sundance Clinical Research

St Louis, Missouri, United States

Site Status

Velocity Clinical Research, Omaha

Omaha, Nebraska, United States

Site Status

South Jersey Infectious Disease

Somers Point, New Jersey, United States

Site Status

Rochester Clinical Research, LLC

Rochester, New York, United States

Site Status

Accellacare - Charlotte

Charlotte, North Carolina, United States

Site Status

PharmQuest Life Sciences, LLC

Greensboro, North Carolina, United States

Site Status

Accellacare - Wilmington

Wilmington, North Carolina, United States

Site Status

Senders Pediatrics

Cleveland, Ohio, United States

Site Status

Centricity Research Columbus Ohio Multispecialty

Columbus, Ohio, United States

Site Status

Kaiser Permanente Northwest Center for Health Research

Portland, Oregon, United States

Site Status

Clinical Neuroscience Solutions Inc.

Memphis, Tennessee, United States

Site Status

Benchmark Research

Austin, Texas, United States

Site Status

Tekton Research, LLC.

Austin, Texas, United States

Site Status

DM Clinical Research - Bellaire

Houston, Texas, United States

Site Status

IMA Clinical Research San Antonio

San Antonio, Texas, United States

Site Status

DM Clinical Research - MDC

Tomball, Texas, United States

Site Status

J. Lewis Research, Inc. / Foothill Family Clinic

Salt Lake City, Utah, United States

Site Status

J. Lewis Research, Inc. / Foothill Family Clinic South

Salt Lake City, Utah, United States

Site Status

Virginia Research Center

Midlothian, Virginia, United States

Site Status

Countries

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United States

References

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Gayed J, Bangad V, Xu X, Mensa F, Cutler M, Tureci O, Sahin U, Modjarrad K, Swanson KA, Anderson AS, Gurtman A, Kitchin N; C4591054 Study Group. Immunogenicity of the Monovalent Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine against XBB.1.5, BA.2.86, and JN.1 Sublineages: A Phase 2/3 Trial. Vaccines (Basel). 2024 Jul 2;12(7):734. doi: 10.3390/vaccines12070734.

Reference Type DERIVED
PMID: 39066372 (View on PubMed)

Gayed J, Diya O, Lowry FS, Xu X, Bangad V, Mensa F, Zou J, Xie X, Hu Y, Lu C, Cutler M, Belanger T, Cooper D, Koury K, Anderson AS, Tureci O, Sahin U, Swanson KA, Modjarrad K, Gurtman A, Kitchin N; C4591054 Study Group. Safety and Immunogenicity of the Monovalent Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine in Individuals >/=12 Years Old: A Phase 2/3 Trial. Vaccines (Basel). 2024 Jan 24;12(2):118. doi: 10.3390/vaccines12020118.

Reference Type DERIVED
PMID: 38400102 (View on PubMed)

Usdan L, Patel S, Rodriguez H, Xu X, Lee DY, Finn D, Wyper H, Lowry FS, Mensa FJ, Lu C, Cooper D, Koury K, Anderson AS, Tureci O, Sahin U, Swanson KA, Gruber WC, Kitchin N; C4591044 Study Group. A Bivalent Omicron-BA.4/BA.5-Adapted BNT162b2 Booster in >/=12-Year-Olds. Clin Infect Dis. 2024 May 15;78(5):1194-1203. doi: 10.1093/cid/ciad718.

Reference Type DERIVED
PMID: 38016021 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://pmiform.com/clinical-trial-info-request?StudyID=C4591044

To obtain contact information for a study center near you, click here.

Other Identifiers

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2022-002008-19

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCT05472038

Identifier Type: REGISTRY

Identifier Source: secondary_id

C4591044

Identifier Type: -

Identifier Source: org_study_id

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