A Study to Learn About New COVD-19 RNA Vaccine Candidates for New Variants in Healthy Individuals

A PHASE 2/3 PROTOCOL TO INVESTIGATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF BNT162b2 RNA-BASED VACCINE CANDIDATES FOR SARS-CoV-2 NEW VARIANTS IN HEALTHY INDIVIDUALS

The purpose of this clinical protocol is to learn about the safety, tolerability, and immunogenicity of new BNT162b2 RNA-based vaccine candidates targeting new variants of SARS-CoV-2 in healthy people.

Substudy A:

• This study will evaluate the safety, tolerability, and immunogenicity of BNT162b2 (Omi XBB.1.5) given as a single 30 µg dose,

  • in people who are 12 years of age and older,
  • who previously received at least 3 doses of a US-authorized mRNA COVID-19 vaccine, with the most recent dose being an Omicron BA.4/BA.5-adapted bivalent vaccine received at least 150 days before the study vaccination (Visit 1).
• The study is about 6 months long for each participant.
• Participants will have at least 5 visits to the clinic.
• At each clinic visit a blood sample will be taken.
• At least 1 nasal swab will taken.

Substudy B:

• This study will evaluate the safety, tolerability, and immunogenicity of BNT162b2 (Omi XBB.1.5) given as a single 30 µg dose,

  • in people who are 12 years of age and older,
  • who are COVID-19 vaccine-naïve
  • who have had any positive SARS-CoV-2 test result >28 days before study vaccine administration.
• The study is about 6 months long for each participant.
• Participants will have at least 5 visits to the clinic.
• At each clinic visit a blood sample will be taken.
• At least 1 nasal swab will taken.

Substudy C:

• This study will evaluate the safety, tolerability, and immunogenicity of BNT162b2 (Omi JN.1) and BNT162b2 (Omi KP.2) given as a single 30 µg dose to:

  • Cohort 1: people who are 18 years of age and older, who will receive BNT162b2 (Omi JN.1), and,
  • Cohort 2: people who are 12 years of age and older, who will receive BNT162b2 (Omi JN.1), and,
  • Cohort 3: people who are 18 years of age and older who will receive BNT162b2 (Omi KP.2).
  • Participants may have never received a COVID-19 vaccine or, may have previously received COVID-19 vaccine(s), with the most recent dose received at least 150 days before the study vaccination (Visit 1).
• The study is about 6 months long for each participant.
• Participants will have at least 6 visits (Cohorts 1 and 3) or at least 5 visits (Cohort 2) to the clinic.
• At each clinic visit a blood sample will be taken.
• At least 1 nasal swab will taken.

Study Overview

• Status: Completed
• Conditions: COVID-19; SARS-CoV-2 Infection
• Intervention / Treatment: Biological: BNT162b2 (Omi XBB.1.5); Biological: BNT162b2 (Omi JN.1); Biological: BNT162b2 (Omi KP.2)

• Study Type: Interventional
• Enrollment (Actual): 1051
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Athens, Alabama, United States, 35611
      • North Alabama Research Center
    • Huntsville, Alabama, United States, 35801
      • Medical Affiliated Research Center
    • Mobile, Alabama, United States, 36608
      • Alliance for Multispecialty Research, LLC
  • Arizona
    • Surprise, Arizona, United States, 85378
      • Epic Medical Research - Surprise
    • Tempe, Arizona, United States, 85281
      • Alliance for Multispecialty Research, LLC
  • California
    • Dublin, California, United States, 94568
      • West Coast Research
    • 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
    • Hialeah, Florida, United States, 33012
      • Indago Research & Health Center, Inc
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc. dba CNS Healthcare
    • Miami, Florida, United States, 33142
      • Acevedo Clinical Research Associates
    • Miami, Florida, United States, 33130
      • Care Research - West Flagler Street
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc.
  • 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
    • Springfield, Missouri, United States, 65802
      • Bio-Kinetic Clinical Applications, LLC dba QPS-MO
    • Springfield, Missouri, United States, 65807
      • Bio-Kinetic Clinical Applications LLC DBA QPS_MO (Patient Screening Only)
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • M3 Wake Research, Inc.
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Centricity Research Columbus Ohio Multispecialty
    • Dayton, Ohio, United States, 45409
      • Dayton Clinical Research
    • South Euclid, Ohio, United States, 44121
      • Senders Pediatrics
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Alliance for Multispecialty Research, LLC
    • Knoxville, Tennessee, United States, 37909
      • Alliance for Multispecialty Research, LLC
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions Inc.
  • Texas
    • Dallas, Texas, United States, 75230
      • Zenos Clinical Research
    • DeSoto, Texas, United States, 75115
      • Epic Medical Research - DeSoto
    • Houston, Texas, United States, 77081
      • DM Clinical Research - Bellaire
    • Mesquite, Texas, United States, 75149
      • SMS Clinical Research
    • San Antonio, Texas, United States, 78229
      • IMA Clinical Research San Antonio
    • Tomball, Texas, United States, 77375
      • DM Clinical Research
  • Utah
    • Layton, Utah, United States, 84041
      • Alliance for Multispecialty Research, LLC
    • 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
    • Norfolk, Virginia, United States, 23502
      • Alliance for Multispecialty Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

SSA

Inclusion Criteria:

• Received at least 3 prior doses of a US-authorized mRNA COVID-19 vaccine, with the most recent dose being a US-authorized Omicron BA.4/BA.5-adapted bivalent vaccine received at least 150 days before Visit 1 (Day 1).
• 12 years of age and older
• Healthy participants (stable pre-existing disease permitted).
• Willing and able to comply with all scheduled visits/contacts, study procedures and lifestyle considerations.
• Capable of giving, or parent(s)/legal guardian capable of giving, signed informed consent.

Exclusion Criteria

• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study vaccines.
• Immunocompromised with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
• Women who are pregnant or breastfeeding.
• Any 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.
• History of myocarditis or pericarditis.
• Receipt of 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.
• Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, used for the treatment or prevention of COVID-19 or those that are considered immunosuppressive, from 60 days before study vaccination or planned receipt throughout the study.
• Participation in other studies involving receipt of other study intervention within 28 days before enrollment. Anticipated participation in other studies involving other study intervention from enrollment through the end of this study.
• 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.

SSB

Inclusion Criteria:

• COVID-19 vaccine-naïve.
• Any positive SARS-CoV-2 test result >28 days before study intervention administration.
• 12 years of age and older.
• Healthy participants (stable pre-existing disease permitted).
• Willing and able to comply with all scheduled visits/contacts, study procedures and lifestyle considerations.
• Capable of giving or parent(s)/legal guardian capable of giving, signed informed consent.

Exclusion Criteria:

• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study vaccines.
• Immunocompromised individuals with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
• Women who are pregnant or breastfeeding.
• Any medical or psychiatric condition, including recent (within the past year) or active suicidal ideation/behavior, or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• History of myocarditis or pericarditis.
• Receipt of 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.
• Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies used for the treatment or prevention of COVID-19 or those that are considered immunosuppressive, from 60 days before study intervention administration or planned receipt throughout the study.
• Participation in other studies involving receipt of other study intervention within 28 days before enrollment. Anticipated participation in other studies involving other study intervention from enrollment through the end of this study.
• 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.

SSC

Inclusion Criteria:

• Cohort 1: 18 years of age and older
• Cohort 2: 12 years of age and older
• Cohort 3: 18 years of age and older
• Healthy participants (stable pre-existing disease permitted).
• Willing and able to comply with all scheduled visits/contacts, study procedures and lifestyle considerations.
• Capable of giving, or parent(s)/legal guardian capable of giving, signed informed consent.

Exclusion Criteria

• History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study vaccines.
• Immunocompromised with known or suspected immunodeficiency, as determined by history and/or laboratory/physical examination.
• Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection.
• Women who are pregnant or breastfeeding.
• Any 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.
• History of myocarditis or pericarditis.
• Receipt of 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.
• Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, used for the treatment or prevention of COVID-19 or those that are considered immunosuppressive, from 60 days before study vaccination or planned receipt throughout the study.
• Receipt of a COVID-19 vaccine less than 150 days before study intervention administration Visit 1 (Day 1).
• Participation in other studies involving receipt of other study intervention within 28 days before enrollment. Anticipated participation in other studies involving other study intervention from enrollment through the end of this study.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SSA: Group 1; Participants 12 years of age and older, COVID-19 vaccine-experienced will receive 30 µg of BNT162b2 (Omi XBB.1.5) at Visit 1.	Biological: BNT162b2 (Omi XBB.1.5); BNT162b2 monovalent (Omicron XBB.1.5)
Experimental: SSB: Group 2; Participants 12 years of age and older who were previously exposed to SARS-CoV-2 and are COVID-19 vaccine-naïve will receive 30 μg of BNT162b2 (Omi XBB.1.5) at Visit 1	Biological: BNT162b2 (Omi XBB.1.5); BNT162b2 monovalent (Omicron XBB.1.5)
Experimental: SSC: Group 3; Cohort 1 - Participants 18 years of age and older will receive 30 µg of BNT162b2 (Omi JN.1) at Visit 1.	Biological: BNT162b2 (Omi JN.1); BNT162b2 monovalent (Omicron JN.1)
Experimental: SSC: Group 4; Cohort 2 - Participants 12 years of age and older will receive 30 µg of BNT162b2 (Omi JN.1) at Visit 1.	Biological: BNT162b2 (Omi JN.1); BNT162b2 monovalent (Omicron JN.1)
Experimental: SSC - Group 5; Cohort 3 - Participants 18 years of age and older who will receive 30 µg of BNT162b2 (Omi KP.2) at Visit 1.	Biological: BNT162b2 (Omi KP.2); BNT162b2 monovalent (Omicron KP.2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Local Reactions Within 7 Days After Vaccination: SSA	Local reactions: pain at injection site, redness and swelling were recorded by participants in an electronic diary (e-diary) or as adverse events (AEs) in the case report form (CRF). Redness and swelling were recorded in measuring device units (mdu) (range: 1 to 21), 1 mdu =0.5 centimeter (cm) and were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] and necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit or hospitalization for severe pain at injection site). Grade 4 local reactions were classified by investigator or medically qualified person.	Day 1 to Day 7 after vaccination
Percentage of Participants With Systemic Events Within 7 Days After Vaccination: SSA	Systemic events were recorded by participants in an e-diary or as AEs in the CRF. Fever: defined as oral temperature more than or equal to (>=38) degree Celsius (C) and categorized as >= 38.0 to 38.4 degree C, >38.4 to 38.9 degree C, >38.9 to 40.0 degree C and >40.0 degree C. Fatigue, headache, chills, new or worsened muscle pain and joint pain were graded as: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity). Vomiting: mild: 1-2 times in 24 hours (h), moderate: >2 times in 24h, severe: required intravenous (IV) hydration. Diarrhea was graded as: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h. Grade 4 for all events except fever: ER visit/hospitalization. Grade 4 systemic events were classified by investigator or medically qualified person.	Day 1 to Day 7 after vaccination
Percentage of Participants With Adverse Events (AEs) From Vaccination Through 1 Month After Vaccination: SSA	An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with use of study intervention, whether or not considered related to study intervention. A serious AE (SAE) was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect, any other event pre-specified in protocol of the study; or considered as an important medical event. AEs included both SAEs and all non-SAEs. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.	From vaccination on Day 1 up to 1 month after vaccination
Percentage of Participants With SAEs From Vaccination Through 6 Months After the Study Vaccination: SSA	An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect, any other event pre-specified in protocol of the study; or considered as an important medical event.	From vaccination on Day 1 up to 6 months after vaccination
Geometric Mean Titers (GMT) of SARS-CoV-2 Omi XBB.1.5-Neutralizing Titers at 1 Month After Vaccination: SSA and Historical Control of the Bivalent BNT162b2 (WT/Omi BA.4/BA.5) Group From Study C4591044	GMTs and 2-sided 95 percentage (%) confidence interval (CIs) were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the lower limit of quantitation (LLOQ) were set to 0.5*LLOQ.	At 1 month after vaccination
GMT of SARS-CoV-2 Omi BA.4/BA.5-Neutralizing Titers at 1 Month After Vaccination: SSA and Historical Control of the Bivalent BNT162b2 (WT/Omi BA.4/BA.5) Group From Study C4591044	GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.	At 1 month after vaccination
Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omi XBB.1.5-Neutralizing Titers From Before Study Vaccination to 1 Month After Vaccination: SSA and Historical Control of Bivalent BNT162b2 (WT/Omi BA.4/BA.5) Group From Study C4591044	GMFRs were defined as geometric mean ratios of the results after vaccination to the results before vaccination. GMFR and 2-sided 95% CI 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.	From before vaccination on Day 1 up to 1 month after vaccination
GMFR of SARS-CoV-2 Omi BA.4/BA.5-Neutralizing Titers From Before Vaccination to 1 Month After Vaccination: SSA and Historical Control of the Bivalent BNT162b2 (WT/Omi BA.4/BA.5) Group From Study C4591044	GMFRs were defined as geometric mean ratios of the results after vaccination to the results before vaccination. GMFR and 2-sided 95% CI 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.	From before vaccination on Day 1 up to 1 month after vaccination
Percentage of Participants With Seroresponse to SARS-CoV-2 Omi XBB.1.5-Neutralizing Titers at 1 Month After Vaccination: SSA and Historical Control of the Bivalent BNT162b2 (WT/Omi BA.4/BA.5) Group From Study C4591044	Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, the postvaccination assay result of >= 4* LLOQ was considered a seroresponse.	At 1 month after vaccination
Percentage of Participants With Seroresponse to SARS-CoV-2 Omi BA.4/BA.5-Neutralizing Titers at 1 Month After Vaccination: SSA and Historical Control of the Bivalent BNT162b2 (WT/Omi BA.4/BA.5) Group From Study C4591044	Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, the postvaccination assay result of >= 4* LLOQ was considered a seroresponse.	At 1 month after vaccination
Percentage of Participants With Local Reactions Within 7 Days After Vaccination: SSB	Local reactions: pain at injection site, redness and swelling were recorded by participants in an e-diary or as AEs in the CRF. Redness and swelling were recorded in mdu (range:1 to 21), 1 mdu= 0.5 cm and were graded as mild (>2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] and necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (ER visit or hospitalization for severe pain at injection site). Grade 4 local reactions were classified by investigator or medically qualified person.	Day 1 to Day 7 after vaccination
Percentage of Participants With Systemic Events Within 7 Days After Vaccination: SSB	Systemic events were recorded by participants in an e-diary or as AEs in the CRF. Fever: defined as oral temperature >=38 degree C and categorized as >= 38.0 to 38.4 degree C, >38.4 to 38.9 degree C, >38.9 to 40.0 degree C and >40.0 degree C. Fatigue, headache, chills, new or worsened muscle pain and joint pain were graded as: mild (didn't interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity). Vomiting: mild: 1-2 times in 24h, moderate: >2 times in 24h, severe: required IV hydration. Diarrhea were graded as: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h. Grade 4 for all events except fever: ER visit/hospitalization. Grade 4 systemic events were classified by investigator or medically qualified person.	Day 1 to Day 7 after vaccination
Percentage of Participants With AEs From Vaccination Through 1 Month After Vaccination: SSB	An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with use of study intervention, whether or not considered related to study intervention. A SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect, any other event pre-specified in protocol of the study; or considered as an important medical event. AEs included both SAEs and all non-SAEs. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.	From vaccination on Day 1 up to 1 month after vaccination
Percentage of Participants With SAEs From Vaccination Through 6 Months After the Study Vaccination: SSB	An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect, any other event pre-specified in protocol of the study; or considered as an important medical event.	From vaccination on Day 1 up to 6 months after vaccination
Geometric Mean Ratio (GMR) of the SARS-CoV-2 XBB.1.5-Neutralizing Titers 1 Month After BNT162b2 (Omi XBB.1.5) COVID-19 Vaccine-Naive Participants in SSB Versus Vaccine-Experienced Participants in SSA	GMTs / GMRs and 2-sided 95% CIs were calculated by exponentiating the least square (LS) means / difference of LS means and the corresponding CIs based on analysis of log-transformed assay results using a linear regression model with baseline assay results (log scale), age and vaccine group as covariates. Assay results below the LLOQ were set to 0.5*LLOQ. GMT was reported in descriptive section and GMR was reported in statistical analysis section	At 1 month after vaccination
Percentage of Participants and Difference in Percentage of Participants With Seroresponse to the XBB.1.5 Strain 1 Month After BNT162b2 (Omi XBB.1.5) COVID-19 Vaccine Naive Participants in SSB Versus Vaccine-Experienced Participants in SSA	Seroresponse was defined as achieving >=4-fold rise from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, the postvaccination assay result of >= 4* LLOQ was considered a seroresponse. Percentage of participants with seroresponse were reported in descriptive section and difference in percentage of participants with seroresponse in SSB: All Age Groups (Vaccine Naive)- SSA: All Age Groups (Vaccine Experienced Control) were reported in statistical analysis section.	At 1 month after vaccination
Percentage of Participants With Local Reactions Within 7 Days After Vaccination: SSC Cohort 2; SSC Cohort 1 and 2 Combined	Local reactions: pain at injection site, redness and swelling were recorded by participants in an e-diary or as AEs in the CRF. Redness and swelling were recorded in mdu (range:1 to 21), 1 mdu= 0.5 cm and were graded as mild (>2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] and necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (ER visit or hospitalization for severe pain at injection site). Grade 4 local reactions were classified by investigator or medically qualified person.	Day 1 to Day 7 after vaccination
Percentage of Participants With Systemic Events Within 7 Days After Vaccination: SSC Cohort 2; SSC Cohort 1 and 2 Combined	Systemic events were recorded by participants in an e-diary or as AEs in the CRF. Fever: defined as oral temperature >=38 degree C and categorized as >= 38.0 to 38.4 degree C, >38.4 to 38.9 degree C, >38.9 to 40.0 degree C and >40.0 degree C. Fatigue, headache, chills, new or worsened muscle pain and joint pain were graded as: mild (didn't interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity). Vomiting: mild: 1-2 times in 24h, moderate: >2 times in 24h, severe: required IV hydration. Diarrhea were graded as: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h. Grade 4 for all events except fever: ER visit/hospitalization. Grade 4 systemic events were classified by investigator or medically qualified person.	Day 1 to Day 7 after vaccination
Percentage of Participants With AEs From Vaccination Through 1 Month After Vaccination: SSC Cohort 2; SSC Cohort 1 and 2 Combined	An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with use of study intervention, whether or not considered related to study intervention. A SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect, any other event pre-specified in protocol of the study; or considered as an important medical event. AEs included both SAEs and all non-SAEs. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.	From vaccination on Day 1 up to 1 month after vaccination
Percentage of Participants With SAEs From Vaccination Through 6 Months After the Study Vaccination: SSC Cohort 2; SSC Cohort 1 and 2 Combined	An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect, any other event pre-specified in protocol of the study; or considered as an important medical event.	From vaccination on Day 1 up to 6 months after vaccination
Percentage of Participants With Local Reactions Within 7 Days After Vaccination: SSC Cohort 3	Local reactions: pain at injection site, redness and swelling were recorded by participants in an e-diary or as AEs in the CRF. Redness and swelling were recorded in mdu (range:1 to 21), 1 mdu= 0.5 cm and were graded as mild (>2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] and necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (ER visit or hospitalization for severe pain at injection site). Grade 4 local reactions were classified by investigator or medically qualified person.	Day 1 to Day 7 after vaccination
Percentage of Participants With Systemic Events Within 7 Days After Vaccination: SSC Cohort 3	Systemic events were recorded by participants in an e-diary or as AEs in the CRF. Fever: defined as oral temperature >=38 deg C and categorized as >= 38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C and >40.0 deg C. Fatigue, headache, chills, new or worsened muscle pain and joint pain: mild (didn't interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity). Vomiting: mild: 1-2 times in 24h, moderate: >2 times in 24h, severe: required IV hydration. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h. Grade 4 for all events except fever: ER visit/hospitalization. Grade 4 events were classified by investigator or medically qualified person.	Day 1 to Day 7 after vaccination
Percentage of Participants With AEs From Vaccination Through 1 Month After Vaccination: SSC Cohort 3	An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with use of study intervention, whether or not considered related to study intervention. A SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect, any other event pre-specified in protocol of the study; or considered as an important medical event. AEs included both SAEs and all non-SAEs. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.	From vaccination on Day 1 up to 1 month after vaccination
Percentage of Participants With SAEs From Vaccination Through 6 Months After the Study Vaccination: SSC Cohort 3	An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect, any other event pre-specified in protocol of the study; or considered as an important medical event.	From vaccination on Day 1 up to 6 months after vaccination
GMTs of SARS-CoV-2 Omi JN.1 and XBB.1.5 Variant-Neutralizing Titers at 1 Month After Vaccination in SSC Cohorts 1 + 2 Combined and Historical Control Group From SSA	GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.	At 1 month after vaccination
GMFR of SARS-CoV-2 Omi JN.1 and XBB.1.5 Variant-Neutralizing Titers From Before Vaccination to 1 Month After Vaccination in SSC Cohorts 1 + 2 Combined and Historical Control Group From SSA	GMFRs were defined as geometric mean ratios of the results after vaccination to the results before 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.	From before Vaccination to 1 month after Vaccination
Percentage of Participants With Seroresponse to SARS-CoV-2 OMI JN.1 and XBB.1.5 Variant-Neutralizing Titers at 1 Month After Vaccination in SSC Cohorts 1 + 2 Combined and Historical Control Group From SSA	Seroresponse was defined as achieving a >=4-fold rise from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, a postvaccination assay result >=4 *LLOQ is considered a seroresponse.	At 1 month after vaccination
GMTs of SARS-CoV-2 Omi KP.2 and Omi JN.1 Variant-Neutralizing Titers at 1 Month After Vaccination in SSC Cohort 3 and SSC Cohorts 1 + 2 Combined as Control	GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ.	At 1 month after vaccination
GMFR of SARS-CoV-2 Omi KP.2 and Omi JN.1 Variant-Neutralizing Titers From Before Vaccination to 1 Month After Vaccination in SSC Cohort 3 and Cohorts 1 + 2 Combined as Control	GMFRs were defined as geometric mean ratios of the results after vaccination to the results before 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.	From before vaccination on Day 1 up to 1 month after vaccination
Percentage of Participants With Seroresponse to SARS-CoV-2 Omi KP.2 and Omi JN.1 Variant-Neutralizing Titers at 1 Month After Vaccination in SSC Cohort 3 and Cohorts 1 + 2 Combined as Control	Seroresponse was defined as achieving a >=4-fold rise from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, a postvaccination assay result >=4 *LLOQ is considered a seroresponse.	At 1 month after 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.
• Diya O, Gayed J, Lowry FS, Ma H, Bangad V, Mensa F, Zou J, Xie X, Hu Y, Cutler M, Belanger T, Cooper D, Xu X, Mogg R, Tureci O, Sahin U, Swanson KA, Modjarrad K, Anderson AS, Gurtman A, Kitchin N. Safety and Immunogenicity of Monovalent Omicron KP.2-Adapted BNT162b2 COVID-19 Vaccine in Adults: Single-Arm Substudy from a Phase 2/3 Trial. Infect Dis Ther. 2025 Aug;14(8):1973-1987. doi: 10.1007/s40121-025-01185-4. Epub 2025 Jul 1.
• Diya O, Gayed J, Lowry FS, Ma H, Bangad V, Mensa F, Zou J, Xie X, Hu Y, Cutler M, Belanger T, Cooper D, Xu X, Koury K, Tureci O, Sahin U, Swanson KA, Modjarrad K, Anderson AS, Gurtman A, Kitchin N. A phase 2/3 trial to investigate the safety and immunogenicity of monovalent Omicron JN.1-adapted BNT162b2 COVID-19 vaccine in adults >/=18 years old. Vaccine. 2025 Apr 11;52:126869. doi: 10.1016/j.vaccine.2025.126869. Epub 2025 Feb 24.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2023
• Primary Completion (Actual): March 13, 2025
• Study Completion (Actual): March 13, 2025

Study Registration Dates

• First Submitted: August 10, 2023
• First Submitted That Met QC Criteria: August 10, 2023
• First Posted (Actual): August 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Vaccine; Coronavirus; COVID-19; RNA Vaccine; Vaccine-naïve
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronaviridae Infections; Nidovirales Infections; COVID-19; Coronavirus Infections; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; COVID-19 Vaccines; Antigens; BNT162 Vaccine
• Other Study ID Numbers: C4591054; 2024-000361-24 (Registry Identifier: EudraCT); NCT05997290 (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