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

AN INTERVENTIONAL, RANDOMIZED, ACTIVE-CONTROLLED, PHASE 1/2/3 STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF BNT162b RNA-BASED VACCINE CANDIDATES IN COVID-19 VACCINE-EXPERIENCED HEALTHY INDIVIDUALS

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).

Study Overview

• Status: Completed
• Conditions: COVID-19; SARS-CoV-2 Infection
• Intervention / Treatment: Biological: BNT162b5 Bivalent (WT/OMI BA.2); Biological: BNT162b2 Bivalent (WT/OMI BA.1); Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5); Biological: BNT162b5 Bivalent (Original/OMI BA.4/BA.5); Biological: BNT162b6 Bivalent (Original/OMI BA.4/BA.5); Biological: BNT162b7 Bivalent (Original/OMI BA.4/BA.5); Biological: BNT162b7 Monovalent (OMI BA.4/BA.5)

• Study Type: Interventional
• Enrollment (Actual): 1453
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
    • San Diego, California, United States, 92123
      • California Research Foundation
    • Valley Village, California, United States, 91607
      • Bayview Research Group, LLC
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Clinical Research Consulting
  • Florida
    • Hollywood, Florida, United States, 33024
      • Research Centers of America ( Hollywood )
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
    • Miami, Florida, United States, 33142
      • Acevedo Clinical Research Associates
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Kentucky Pediatric/ Adult Research
  • Missouri
    • Chesterfield, Missouri, United States, 63005
      • Clinical Research Professionals
    • St Louis, Missouri, United States, 63141
      • Sundance Clinical Research
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Velocity Clinical Research, Omaha
  • New Jersey
    • Somers Point, New Jersey, United States, 08244
      • South Jersey Infectious Disease
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, LLC
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • Accellacare - Charlotte
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest Life Sciences, LLC
    • Wilmington, North Carolina, United States, 28401
      • Accellacare - Wilmington
  • Ohio
    • Cleveland, Ohio, United States, 44121
      • Senders Pediatrics
    • Columbus, Ohio, United States, 43213
      • Centricity Research Columbus Ohio Multispecialty
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest Center for Health Research
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions Inc.
  • Texas
    • Austin, Texas, United States, 78705
      • Benchmark Research
    • Austin, Texas, United States, 78745
      • Tekton Research, LLC.
    • Houston, Texas, United States, 77081
      • DM Clinical Research - Bellaire
    • San Antonio, Texas, United States, 78229
      • Ima Clinical Research San Antonio
    • Tomball, Texas, United States, 77375
      • DM Clinical Research - MDC
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research, Inc. / Foothill Family Clinic
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research, Inc. / Foothill Family Clinic South
  • Virginia
    • Midlothian, Virginia, United States, 23114
      • Virginia Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: BNT162b5 Bivalent (WT/OMI BA.2); Participants will receive 30 µg of BNT162b5 Bivalent (WT/OMI BA.2) at Visit 1.	Biological: BNT162b5 Bivalent (WT/OMI BA.2); BNT162b5 Wild Type and BNT162b5 OMICRON [B.1.1.529 sublineage BA.2]
Experimental: Cohort 1: BNT162b2 Bivalent (WT/OMI BA.1); Participants will receive 30 µg of BNT162b2 Bivalent (WT/OMI BA.1) at Visit 1.	Biological: BNT162b2 Bivalent (WT/OMI BA.1); BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.1]
Experimental: 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.	Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5); BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
Experimental: 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.	Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5); BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
Experimental: 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.	Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5); BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
Experimental: 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.	Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5); BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
Experimental: 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.	Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5); BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
Experimental: 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.	Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5); BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
Experimental: Cohort 3 - Group 2: >55 years; 30 µg; Participants will receive BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 µg at Visit 1.	Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5); BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
Active Comparator: 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	Biological: BNT162b2 Bivalent (WT/OMI BA.4/BA.5); BNT162b2 Wild Type and BNT162b2 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
Experimental: 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	Biological: BNT162b5 Bivalent (Original/OMI BA.4/BA.5); BNT162b5 Wild Type and BNT162b5 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
Experimental: 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	Biological: BNT162b6 Bivalent (Original/OMI BA.4/BA.5); BNT162b6 Wild Type and BNT162b6 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
Experimental: 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	Biological: BNT162b7 Bivalent (Original/OMI BA.4/BA.5); BNT162b7 Wild Type and BNT162b7 OMICRON [B.1.1.529 sublineage BA.4/BA.5]
Experimental: 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	Biological: BNT162b7 Monovalent (OMI BA.4/BA.5); BNT162b7 OMICRON [B.1.1.529 sublineage BA.4/BA.5]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination	Local reactions were recorded by participants in an electronic diary (e-diary). Local reactions included redness, swelling and pain at injection site. Redness and swelling were graded as mild: greater than (>) 2.0 to 5.0 centimeter (cm), moderate: >5.0 to 10.0 cm, severe: >10.0 cm, grade 4 (potentially life threatening): necrosis or exfoliative dermatitis (redness) and necrosis (swelling). Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity and grade 4 (potentially life threatening): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Local reactions reported as adverse events (AEs) in the case report form within 7 days after the study vaccination were also reported.	From Day 1 to Day 7 after study vaccination
Cohort 1: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination	Systemic events were recorded by participants in an e-diary. Fever was oral temperature greater than or equal to (>=) 38 degree Celsius (deg C) and categorized as >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24 hours (h), moderate: >2 times in 24h and severe: required intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h. For all systemic events except fever, Grade 4= emergency room visit or hospitalization. Grade 4 events were classified by the investigator/medically qualified person. Systemic events reported as AEs in the CRF within 7 days after vaccination were also reported.	From Day 1 to Day 7 after study vaccination
Cohort 1: Percentage of Participants With Adverse Events (AEs) From Study Vaccination Through 1 Month After Study Vaccination	An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Results excluded local reactions and systemic events data.	From study vaccination on Day 1 through 1 month after study vaccination
Cohort 1: Percentage of Participants With Serious Adverse Events (SAEs) From Study Vaccination Through 6 Months After Study Vaccination	An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was an AE that resulted in death, was life-threatening, resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event, medical event was judged by investigator; required inpatient hospitalization or prolongation of existing hospitalization.	From study vaccination on Day 1 through 6 months after study vaccination
Cohort 1: Geometric Mean Titer (GMT) of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain Neutralizing Titers (NTs) at Baseline- Participants Without Evidence of Infection	GMTs and the corresponding 2-sided confidence intervals (CIs) were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on student's t distribution). Assay results below the lower limit of quantification (LLOQ) were set to 0.5*LLOQ.	At baseline (before study vaccination)
Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at Baseline- Participants With or Without Evidence of Infection	GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on student's t distribution).	At baseline (before study vaccination)
Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at 1 Month After Study Vaccination- Participants Without Evidence of Infection	GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.	1 month after the study vaccination
Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at 1 Month After Study Vaccination- Participants With or Without Evidence of Infection	GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.	1 month after the study vaccination
Cohort 1: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain- NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants Without Evidence of Infection	GMFR from before study vaccination to 1 month after study vaccination for each strain-specific neutralizing titer was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating mean logarithm of fold rises and corresponding CIs (based on student-t distribution). Assay results below lower limit of quantitation (LLOQ) were set to 0.5*LLOQ in analysis.	From before the study vaccination to 1 month after the study vaccination
Cohort 1: GMFR of SARS-CoV-2 Omicron Strain (BA.1 and BA2) and Reference Strain- NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants With or Without Evidence of Infection	GMFR from before study vaccination to 1 month after study vaccination for each strain-specific neutralizing titer was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating mean logarithm of fold rises and corresponding CIs (based on student-t distribution). Assay results below LLOQ were set to 0.5*LLOQ in analysis.	From before the study vaccination to 1 month after the study vaccination
Cohort 1: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain- NTs at 1 Month After Study Vaccination- Participants Without Evidence of Infection	Seroresponse was defined as achieving >= 4-fold rise in NTs from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, the postvaccination measure of >= 4*LLOQ was considered a seroresponse.	1 month after the study vaccination
Cohort 1: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain- NTs at 1 Month After Study Vaccination- Participants With or Without Evidence of Infection	Seroresponse was defined as achieving >= 4-fold rise in NTs from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, the postvaccination measure of >= 4*LLOQ was considered a seroresponse.	1 month after the study vaccination
Cohort 2: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination	Local reactions were recorded by participants in an e-diary. Local reactions included redness, swelling and pain at injection site. Redness and swelling were graded as mild: > 2.0 to 5.0 cm, moderate: >5.0 to 10.0 cm, severe: >10.0 cm, grade 4 (potentially life threatening): necrosis or exfoliative dermatitis (redness) and necrosis (swelling). Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity and grade 4 (potentially life threatening): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Local reactions reported as AEs in the case report form within 7 days after the study vaccination were also reported.	From Day 1 to Day 7 after study vaccination
Cohort 2: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination	Systemic events were recorded by participants in an e-diary. Fever was oral temperature >= 38 deg C and categorized as >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24h, moderate: >2 times in 24h and severe: required intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h. For all systemic events except fever, Grade 4= emergency room visit or hospitalization. Grade 4 events were classified by the investigator or medically qualified person. Systemic events reported as AEs in the CRF within 7 days after vaccination were also reported.	From Day 1 to Day 7 after study vaccination
Cohort 2: Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination	An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Results excluded local reactions and systemic events data.	From study vaccination through 1 month after study vaccination
Cohort 2: Percentage of Participants With SAEs From Study Vaccination Through 6 Month After Study Vaccination	An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was an AE that resulted in death, was life-threatening, resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization.	From study vaccination through 6 months after study vaccination
Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination	Local reactions were recorded by participants in an e-diary. Local reactions included redness, swelling and pain at injection site. Redness and swelling were graded as mild: >2.0 to 5.0 cm, moderate: >5.0 to 10.0 cm, severe: >10.0 cm, grade 4 (potentially life threatening): necrosis or exfoliative dermatitis (redness) and necrosis (swelling). Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity and grade 4 (potentially life threatening): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Local reactions reported as AEs in the case report form within 7 days after the study vaccination were also reported.	From Day 1 to Day 7 after study vaccination
Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination	Systemic events were recorded by participants in an e-diary. Fever was oral temperature >= 38 deg C and categorized as >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24 h, moderate: >2 times in 24h and severe: required intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h. For all systemic events except fever, Grade 4= emergency room visit or hospitalization. Grade 4 events were classified by the investigator/medically qualified person. Systemic events reported as AEs in the CRF within 7 days after vaccination were also reported.	From Day 1 to Day 7 after study vaccination
Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination	An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Results excluded local reactions and systemic events data.	From study vaccination through 1 month after study vaccination
Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants With SAEs From Study Vaccination Through 6 Month After Study Vaccination	An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was an AE that resulted in death, was life-threatening, resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization.	From study vaccination through 6 months after study vaccination
GMR of Omicron (BA.4/BA.5)- NT of BNT162b2 Bivalent [WT/ OMI BA.4/ BA.5] 30 mcg Cohort 2 (Group 4)/ Cohort 3 (Group 2) Combined in C4591044 Compared to NT of BNT162b2 30 mcg in C4591031 [NCT04955626]- 1 Month After Vaccination Among Participants >55 Years	Model based GMT of OMI BA.4/BA.5 NTs induced by BNT162b2 Bivalent 30mcg groups of study C4591044 Cohort 2/3 combined and BNT162b2 30mcg of study C4591031 [NCT04955626] Substudy E among participants >55 years are reported as descriptive data. GMTs and 95% CIs were calculated by exponentiating least square (LS) means and corresponding CI based on analysis of logarithmically transformed NT using a linear regression model with terms of baseline NT (log scale) and vaccine group. Assay results below LLOQ were set to 0.5*LLOQ. Model based geometric mean ratio (GMR) are reported in statistical section: OMI BA.4/BA.5 NTs induced 1 month post BNT162b2 Bivalent vaccination in study C4591044 to 1 month post BNT162b2 vaccination in study C4591031 [NCT04955626] among participants >55 years. Outcome measure was planned per protocol to be analyzed in participants of Cohort 2 (Group 4) + Cohort 3 (Group 2) of C4591044 and BNT162b2 experienced participants of study C4591031 [NCT04955626] (control arm).	1 month after study vaccination
Difference in Percentage of Participants With Seroresponse to OMI BA.4/BA.5 for BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg Cohort2(Group4)/Cohort3(Group2)Combined in C4591044 and BNT162b2 30mcg in C4591031-1 Month After Vaccination in Participants >55 Years	Seroresponse: achieving >=4-fold rise in NTs from baseline (before study vaccination). If baseline measurement was below LLOQ, postvaccination measure of >= 4*LLOQ was considered seroresponse. Percentage of participants with seroresponse to OMI BA.4/BA.5 for BNT162b2 Bivalent 30 mcg in Study C4591044 [NCT05472038] Cohort 2/3 combined and BNT162b2 30 mcg in Study C4591031 [NCT04955626] Substudy E among participants >55 years of age are presented as descriptive data. Adjusted difference in seroresponse rate to OMI BA.4/BA.5 between BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg 1 month after vaccination in study C4591044 and 1 month after BNT162b2 vaccination in study C4591031 [NCT04955626] among participants >55 years of age is reported in statistical section. Outcome measure was planned per protocol to be analyzed in participants from Cohort 2 (Group 4) + Cohort 3 (Group 2) and control arm of BNT162b2 experienced participants >55 years of age from study C4591031 [NCT04955626] Substudy E.	1 month after study vaccination
GMR of Omicron (BA.4/BA.5)- NTs of BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg Cohort2 (Group2)/Cohort3 (Group1)Combined for 18-55 Years Compared to BNT162b2 30mcg Cohort2 (Group4)/Cohort3 (Group2)Combined for >55 Years- 1 Month After Vaccination in C4591044	Model based GMT of OMI BA.4/BA.5 NTs induced by BNT162b2 Bivalent 30 mcg groups of study C4591044 [NCT05472038] Cohort 2/3 combined in participants 18-55 years of age compared to participants >55 years of age are presented as descriptive data. GMTs and 2-sided 95% CIs were calculated by exponentiating LS means and corresponding CIs based on analysis of logarithmically transformed NT using a linear regression model with terms of baseline NT (log scale) and vaccine group. Assay results below LLOQ were set to 0.5*LLOQ. Model based GMR: OMI BA.4/BA.5 NTs induced 1 month after BNT162b2 Bivalent vaccination in study C4591044 among participants 18-55 years of age compared to participants >55 years of age is reported in statistical section. The outcome measure was planned per protocol to be analyzed in participants combined from Cohort 2 (Group 2) + Cohort 3 (Group 1) and Cohort 2 (Group 4) + Cohort 3 (Group 2).	1 month after study vaccination
Difference in Percentage of Participants With Seroresponse to OMI BA.4/BA.5 of BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg Cohort2 (Group2)/Cohort3 (Group1) 18-55 Years and Cohort2 (Group4)/Cohort3 (Group2) >55 Years- 1 Month After Vaccination in C4591044	Seroresponse was defined as achieving >= 4-fold rise in NTs from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, the postvaccination measure of >= 4*LLOQ was considered a seroresponse. Percentage of participants with seroresponse to OMI BA.4/BA.5 for BNT162b2 Bivalent 30 mcg in Study C4591044 [NCT05472038] Cohort 2/3 combined in participants 18-55 years of age compared to participants >55 years of age are presented as descriptive data. Adjusted difference in seroresponse rate to OMI BA.4/BA.5 between BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg 1 month after vaccination in study C4591044 in participants 18-55 years of age compared to participants >55 years of age is reported in statistical section. The outcome measure was planned per protocol to be analyzed in participants combined from Cohort 2 (Group 2) + Cohort 3 (Group 1) and Cohort 2 (Group 4) + Cohort 3 (Group 2).	1 month after study vaccination
Cohort 2: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain NTs at Baseline- Participants With or Without Evidence of Infection	GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on student's t distribution). This outcome measure was planned per protocol to be analyzed in participants from Cohort 2 and control arms of BNT162b2 Bivalent (WT/OMI BA.1) experienced participants from study C4591031 [NCT04955626] Substudy E.	At baseline (before study vaccination)
Cohort 2: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain NTs at 1 Month- Participants With or Without Evidence of Infection	GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on student's t distribution). This outcome measure was planned per protocol to be analyzed in participants from Cohort 2 and control arms of BNT162b2 experienced participants from study C4591031 [NCT04955626] Substudy E.	1 month after the study vaccination
Cohort 2: GMFR of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain- NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants With or Without Evidence of Infection	GMFR from before the study vaccination to 1 month after the study vaccination for each strain-specific neutralizing titer was reported in this outcome measure. GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the student-t distribution). Assay results below the LLOQ were set to 0.5*LLOQ in the analysis. This outcome measure was planned per protocol to be analyzed in participants from Cohort 2 and control arms of BNT162b2 experienced participants from study C4591031 [NCT04955626] Substudy E.	From before the study vaccination to 1 month after the study vaccination
Cohort 2: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain- NTs at 1 Month After Study Vaccination- Participants With or Without Evidence of Infection	Seroresponse was defined as achieving >= 4-fold rise in NTs from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, the postvaccination measure of >= 4*LLOQ was considered a seroresponse. Percentage of participants with seroresponse to OMI BA.4/BA.5 for BNT162b2 Bivalent 30 and 60 mcg in Study C4591044 [NCT05472038] Cohort 2 and BNT162b2 30 mcg in Study C4591031 [NCT04955626] Substudy E are presented as descriptive data. This outcome measure was planned per protocol to be analyzed in participants from Cohort 2 and control arms of BNT162b2 experienced participants 18-55 years of age and >55 years of age from study C4591031 [NCT04955626] Substudy E.	1 month after the study vaccination
Cohort 4: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination	Local reactions were recorded by participants in an e-diary. Local reactions included redness, swelling and pain at injection site. Redness and swelling were graded as mild: >2.0 to 5.0 cm, moderate: >5.0 to 10.0 cm, severe: >10.0 cm, grade 4 (potentially life threatening): necrosis or exfoliative dermatitis (redness) and necrosis (swelling). Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity and grade 4 (potentially life threatening): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Local reactions reported as AEs in the case report form within 7 days after the study vaccination were also reported.	From Day 1 to Day 7 after study vaccination
Cohort 4: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination	Systemic events were recorded by participants in an e-diary. Fever was oral temperature >= 38 deg C and categorized as >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and new or worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity and severe: prevented daily routine activity. Vomiting was graded as mild: 1 to 2 times in 24h, moderate: >2 times in 24h and severe: required intravenous hydration. Diarrhea was graded as mild: 2 to 3 loose stools in 24h, moderate: 4 to 5 loose stools in 24h and severe: 6 or more loose stools in 24h. For all systemic events except fever, Grade 4= emergency room visit or hospitalization. Grade 4 events were classified by the investigator or medically qualified person. Systemic events reported as AEs in the CRF within 7 days after vaccination were also reported.	From Day 1 to Day 7 after study vaccination
Cohort 4: Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination	An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Results excluded local reactions and systemic events data.	From study vaccination through 1 month after study vaccination
Cohort 4: Percentage of Participants With SAEs From Study Vaccination Through 6 Months After Study Vaccination	An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was an AE that resulted in death, was life-threatening, resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization.	From study vaccination through 6 months after study vaccination
Cohort 4: GMT of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain NTs at Baseline- Participants With or Without Evidence of Infection	GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on student's t distribution).	At baseline (before study vaccination)
Cohort 4: GMT of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain NTs at 1 Month After Study Vaccination- Participants With or Without Evidence of Infection	GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on student's t distribution).	1 month after the study vaccination
Cohort 4: GMFR of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain- NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants With or Without Evidence of Infection	GMFR from before study vaccination to 1 month after study vaccination for each strain-specific neutralizing titer was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating mean logarithm of fold rises and corresponding CIs (based on student-t distribution). Assay results below LLOQ were set to 0.5*LLOQ in analysis.	From before the study vaccination to 1 month after study vaccination
Cohort 4: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain- NTs at 1 Month After Study Vaccination- Participants With or Without Evidence of Infection	Seroresponse was defined as achieving >= 4-fold rise in NTs from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, the postvaccination measure of >= 4*LLOQ was considered a seroresponse.	1 month after study vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMR of the Reference-Strain- NTs of BNT162b2 [WT/OMI BA.4/BA.5] 30mcg Cohort 2 (Group 4)/ Cohort 3 (Group 2) Combined in C4591044 Compared to NT of BNT162b2 30mcg in C4591031 [NCT04955626] >55 Years of Age- 1 Month After Vaccination	Model based GMT of reference strain NTs induced by BNT162b2 Bivalent 30mcg groups of study C4591044 [NCT05472038] Cohort 2/3 combined and BNT162b2 30 mcg of study C4591031 [NCT04955626] Substudy E among participants >55 years of age presented as descriptive data. GMTs, 2-sided 95% CIs calculated by exponentiating LS means, corresponding CIs based on analysis of logarithmically transformed NT using linear regression model with terms of baseline NT (log scale), vaccine group. Assay results below LLOQ set to 0.5*LLOQ. Model based GMR: OMI BA.4/BA.5 NTs induced 1 month after BNT162b2 Bivalent vaccination in study C4591044 to 1 month after BNT162b2 vaccination in study C4591031 [NCT04955626] among participants >55 years of age reported in statistical section. Outcome measure was planned per protocol to be analyzed in participants from Cohort 2 (Group 4) + Cohort 3 (Group 2) and control arm of BNT162b2 experienced participants >55 years of age from study C4591031 [NCT04955626] Substudy E.	1 month after study vaccination
Cohort 2 (Group 2) + Cohort 3 (Group 1) Combined and Cohort 2 (Group 4) + Cohort 3 (Group 2) Combined: GMT of Omicron BA.4/BA.5 and Reference Strain NT at Baseline and 1 Month After the Study Vaccination	GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on student's t distribution). This outcome measure was planned per protocol to be analyzed in participants from Cohort 2 (Group 2) + Cohort 3 (Group 1), Cohort 2 (Group 4) + Cohort 3 (Group 2) and control arm of BNT162b2 experienced participants >55 years of age from study C4591031 [NCT04955626] Substudy E.	At baseline and 1 month after study vaccination
Cohort 2 (Group 2) + Cohort 3 (Group 1) Combined and Cohort 2 (Group 4) + Cohort 3 (Group 2) Combined: GMFR of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain- NTs From Before the Study Vaccination to 1 Month After the Study Vaccination	GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ in the analysis. GMFR from before the study vaccination to 1 month after study vaccination for Omicron BA.4/BA.5 and reference strain neutralizing titer was reported in this outcome measure. This outcome measure was planned per protocol to be analyzed in participants from Cohort 2 (Group 2) + Cohort 3 (Group 1), Cohort 2 (Group 4) + Cohort 3 (Group 2) and control arm of BNT162b2 experienced participants >55 years of age from study C4591031 [NCT04955626] Substudy E.	From before the study vaccination to 1 month after study vaccination
Cohort 2 (Group 2) + Cohort 3 (Group 1) Combined and Cohort 2 (Group 4) + Cohort 3 (Group 2) Combined: Percentages of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain- NTs at 1 Month After the Study Vaccination	Seroresponse was defined as achieving >= 4-fold rise in NTs from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, the postvaccination measure of >= 4*LLOQ was considered a seroresponse. Percentage of participants with seroresponse to OMI BA.4/BA.5 for BNT162b2 Bivalent 30 mcg in Study C4591044 [NCT05472038] Cohort 2/3 combined and BNT162b2 30 mcg in Study C4591031 [NCT04955626] Substudy E among participants >55 years of age are presented as descriptive data. This outcome measure was planned per protocol to be analyzed in participants from Cohort 2 (Group 2) + Cohort 3 (Group 1), Cohort 2 (Group 4) + Cohort 3 (Group 2) and control arm of BNT162b2 experienced participants >55 years of age from study C4591031 [NCT04955626] Substudy E.	1 month after the study vaccination

Collaborators and Investigators

• Sponsor: BioNTech SE
• Collaborators: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2022
• Primary Completion (Actual): March 26, 2024
• Study Completion (Actual): March 26, 2024

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: July 22, 2022
• First Posted (Actual): July 25, 2022

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 10, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: COVID-19; SARS-CoV-2 infection
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19
• Other Study ID Numbers: C4591044; 2022-002008-19 (Registry Identifier: EudraCT); NCT05472038 (Registry Identifier: ClinicalTrials.gov)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No