A Study to Evaluate the Safety, Tolerability, and Immunogenicity of Combined Modified RNA Vaccine Candidates Against COVID-19 and Influenza

Not Applicable

Completed

Conditions: COVID-19
Influenza, Human

Interventions: Biological: bivalent BNT162b2 (original/Omi BA.4/BA.5)
Biological: QIV
Biological: qIRV (22/23)
Biological: tIRV
Biological: bIRV

Registration Number: NCT05596734

Lead Sponsor: BioNTech SE

Brief Summary: Substudy A: This is a Phase 1 randomized, open-label study to describe the safety and immunogenicity of up to 3 dose- level combinations of modRNA quadrivalent influenza vaccine (qIRV (22/23)) and bivalent BNT162b2 (original/Omi BA.4/BA.5). Participants will receive either:

* qIRV (22/23)/bivalent BNT162b2 (original/Omi BA.4/BA.5), at 1 of the 3 dose-level combinations

* qIRV (22/23) at dose level 1,

* qIRV (22/23) at dose level 2, or

* bivalent BNT162b2 (original/Omi BA.4/BA.5) at dose level 1 administered concurrently in the opposite arm to commercially licensed quadrivalent influenza vaccine (QIV).

Substudy B: This Phase 1/2 study will describe the safety, tolerability, and immunogenicity of quadrivalent influenza vaccine (qIRV)/bivalent BNT162b2 (original/Omi BA.4/BA.5), trivalent influenza vaccine (tIRV)/bivalent BNT162b2 (original/Omi BA.4/BA.5), and bivalent influenza vaccine (bIRV)/bivalent BNT162b2 (original/Omi BA.4/BA.5) when given concurrently with licensed quadrivalent influenza vaccine (QIV).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1019

Inclusion Criteria

Male or female participants 18 years of age and older
Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
Capable of giving signed informed consent as described in the protocol.
For participants 18 through 64 years of age: participants who have received 3 prior doses of 30 µg BNT162b2, with the last dose being 150 to 365 days before Visit 1 (Day 1).
For participants 65 years of age and older: participants who have received 4 or 5 prior doses of a modRNA SARS-CoV-2 vaccine, with the last dose being a bivalent vaccine, 120 days to 365 days before Visit 1 (Day 1).
For Participants 65 years of age and older: receipt of licensed influenza vaccination for the 2022-2023 northern hemisphere season 120 days or more before study intervention administration.

SSA:

Exclusion Criteria

History of severe adverse reaction associated with any vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
Immunocompromised individuals with known or suspected immunodeficiency.
Bleeding diathesis or condition associated with prolonged bleeding.
Women who are pregnant or breastfeeding.
Allergy to egg proteins (egg or egg products) or chicken proteins.
Other 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.
Receipt of chronic systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days before enrollment through conclusion of the study.
Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or planned receipt throughout the study.
For participants 18 through 64 years of age: vaccination with any investigational or licensed influenza vaccine within 6 months (175 days) before study intervention administration.
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.
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.
Participation in strenuous or endurance exercise through Visit 3 of the study.
Prior history of heart disease.
Any abnormal screening troponin I laboratory value.
Screening 12-lead ECG that, as judged by the investigator, is consistent with probable or possible myocarditis or pericarditis, or demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.

SSB: Inclusion Criteria

Male or female participants 18 years of age and older
Participants who are willing and able to comply with all scheduled visits, investigational plan, laboratory tests, lifestyle considerations, and other study procedures.
Healthy participants who are determined by medical history, physical examination (if required), and clinical judgment of the investigator to be eligible for inclusion in the study.
Capable of giving signed informed consent as described in the protocol.
Participants who have received at least 3 prior US-authorized mRNA COVID-19 vaccines, with the last dose being an updated (bivalent) vaccine given at least 150 days before Day 1.

SSB: Exclusion Criteria

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 severe adverse reaction associated with any vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention(s).
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
Receipt of chronic systemic treatment with known immunosuppressant medications (including cytotoxic agents or systemic corticosteroids), or radiotherapy, within 60 days before enrollment through conclusion of the study.
Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or planned receipt throughout the study.
Vaccination with any investigational or licensed influenza vaccine within 6 months (175 days) before study intervention administration, or ongoing receipt of chronic antiviral therapy with activity against influenza
Participation in other studies involving administration of a study intervention within 28 days prior to, and/or during, participation in 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.
Initial enrollment only: Participation in strenuous or endurance exercise through Visit 3 (initial enrollment phase).
Initial enrollment only: Prior history of heart disease of concern
Initial enrollment only: Screening 12-lead ECG that, as judged by the investigator, is consistent with probable or possible myocarditis or pericarditis, or demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SSB: QIV + bivalent BNT162b2 (original/Omi BA.4/BA.5)	QIV	BNT162b2 administered intramuscularly into the deltoid muscle of the right arm, QIV administered intramuscularly into the deltoid muscle of the left arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 4	qIRV (22/23)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: QIV + bivalent BNT162b2 (original/Omi BA.4/BA.5)	bivalent BNT162b2 (original/Omi BA.4/BA.5)	BNT162b2 administered intramuscularly into the deltoid muscle of the right arm, QIV administered intramuscularly into the deltoid muscle of the left arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 5	qIRV (22/23)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 6	bivalent BNT162b2 (original/Omi BA.4/BA.5)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 6	qIRV (22/23)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: tIRV/bivalent BNT162b2(original/Omi\BA.4/BA.5)	tIRV	Administered intramuscularly into the deltoid muscle of the right arm
SSA: qIRV + bivalent BNT162b2 (dose level combination 2)	bivalent BNT162b2 (original/Omi BA.4/BA.5)	Administered intramuscularly into the deltoid muscle of the right arm
SSA: qIRV + bivalent BNT162b2 (dose level combination 2)	qIRV (22/23)	Administered intramuscularly into the deltoid muscle of the right arm
SSA: qIRV + bivalent BNT162b2 (dose level combination 3)	bivalent BNT162b2 (original/Omi BA.4/BA.5)	Administered intramuscularly into the deltoid muscle of the right arm
SSA: qIRV + bivalent BNT162b2 (dose level combination 3)	qIRV (22/23)	Administered intramuscularly into the deltoid muscle of the right arm
SSA: qIRV (dose level 2)	qIRV (22/23)	Administered intramuscularly into the deltoid muscle of the right arm
SSA: bivalent BNT162b2 (dose level 1) + QIV	bivalent BNT162b2 (original/Omi BA.4/BA.5)	BNT162b2 administered intramuscularly into the deltoid muscle of the right arm, QIV administered intramuscularly into the deltoid muscle of the left arm
SSA: bivalent BNT162b2 (dose level 1) + QIV	QIV	BNT162b2 administered intramuscularly into the deltoid muscle of the right arm, QIV administered intramuscularly into the deltoid muscle of the left arm
SSB: QIV + bIRV/bivalent BNT162b2 (original/Omi BA.4/BA.5)	bivalent BNT162b2 (original/Omi BA.4/BA.5)	BNT162b2 administered intramuscularly into the deltoid muscle of the right arm, QIV administered intramuscularly into the deltoid muscle of the left arm
SSB: QIV + bIRV/bivalent BNT162b2 (original/Omi BA.4/BA.5)	QIV	BNT162b2 administered intramuscularly into the deltoid muscle of the right arm, QIV administered intramuscularly into the deltoid muscle of the left arm
SSB: QIV + bIRV/bivalent BNT162b2 (original/Omi BA.4/BA.5)	bIRV	BNT162b2 administered intramuscularly into the deltoid muscle of the right arm, QIV administered intramuscularly into the deltoid muscle of the left arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 1	bivalent BNT162b2 (original/Omi BA.4/BA.5)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 1	qIRV (22/23)	Administered intramuscularly into the deltoid muscle of the right arm
SSA: qIRV + bivalent BNT162b2 (dose level combination 1)	bivalent BNT162b2 (original/Omi BA.4/BA.5)	Administered intramuscularly into the deltoid muscle of the right arm
SSA: qIRV (dose level 1)	qIRV (22/23)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: qIRV	qIRV (22/23)	Administered intramuscularly into the deltoid muscle of the right arm
SSA: qIRV + bivalent BNT162b2 (dose level combination 1)	qIRV (22/23)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 2	bivalent BNT162b2 (original/Omi BA.4/BA.5)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 2	qIRV (22/23)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 3	bivalent BNT162b2 (original/Omi BA.4/BA.5)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 3	qIRV (22/23)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 4	bivalent BNT162b2 (original/Omi BA.4/BA.5)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 5	bivalent BNT162b2 (original/Omi BA.4/BA.5)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 7	bivalent BNT162b2 (original/Omi BA.4/BA.5)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 7	qIRV (22/23)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 8	bivalent BNT162b2 (original/Omi BA.4/BA.5)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: qIRV/bivalent BNT162b2 (original/ Omi BA.4/BA.5) at dose-level combination 8	qIRV (22/23)	Administered intramuscularly into the deltoid muscle of the right arm
SSB: tIRV/bivalent BNT162b2(original/Omi\BA.4/BA.5)	bivalent BNT162b2 (original/Omi BA.4/BA.5)	Administered intramuscularly into the deltoid muscle of the right arm

Primary Outcome Measures

Name	Time	Method
SSA: Percentage of Participants With Local Reactions up to 7 Days Following Vaccination (18-64 Years)	SSA: From Day 1 to Day 7 after Vaccination	Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 centimeter (cm). Redness and swelling were graded as mild (Grade 1): greater than (\>) 2.0 cm to 5.0 cm; moderate (Grade 2): \>5.0 cm to 10.0 cm; severe (Grade 3): \>10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis (redness) and necrosis (swelling). Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Percentage of participants with any local reactions were reported in this outcome measure.
SSA: Percentage of Participants With Local Reactions up to 7 Days Following Vaccination (>=65 Years)	SSA: From Day 1 to Day 7 after Vaccination	Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 cm. Redness and swelling were graded as mild (Grade 1): \>2.0 cm to 5.0 cm; moderate (Grade 2): \>5.0 cm to 10.0 cm; severe (Grade 3): \>10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Percentage of participants with any local reactions were reported in this outcome measure.
SSA: Percentage of Participants With Systemic Events up to 7 Days Following Vaccination (18-64 Years)	SSA: From Day 1 to Day 7 after Vaccination	Systemic events included fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and new or worsened joint pain. Events were recorded by participants in an electronic diary. Fever defined as oral temperature \>=38.0 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. Vomiting graded as: G1: 1-2 times in 24 h; G2: \>2 times in 24h; G3: required IV hydration. Diarrhea graded as: G1: 2-3 loose stools in 24h; G2: 4-5 loose stools in 24h; G3: 6 or more loose stools in 24h.Headache, fatigue, chills, new/worsened muscle pain and new/worsened joint pain: G1: didn't interfere with activity; G2: some interference with activity; G3: prevented daily routine activity. For all systemic events except fever, Grade 4=emergency room visit or hospitalization. Grade 4 events were classified by the investigator. Percentage of participants with any systemic events were reported in this outcome measure.
SSA: Percentage of Participants With Systemic Events up to 7 Days Following Vaccination (>=65 Years)	SSA: From Day 1 to Day 7 after Vaccination	Systemic events included fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and new or worsened joint pain. Events were recorded by participants in an electronic diary. Fever defined as oral temperature \>=38.0 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. Vomiting graded as: G1: 1-2 times in 24 h; G2: \>2 times in 24h; G3: required IV hydration. Diarrhea graded as: G1: 2-3 loose stools in 24h; G2: 4-5 loose stools in 24h; G3: 6 or more loose stools in 24h.Headache, fatigue, chills, new/worsened muscle pain and new/worsened joint pain: G1: didn't interfere with activity; G2: some interference with activity; G3: prevented daily routine activity. For all systemic events except fever, Grade 4=emergency room visit or hospitalization. Grade 4 events were classified by the investigator. Percentage of participants with any systemic events were reported in this outcome measure.
SSA: Percentage of Participants Reporting AEs From Vaccination Through 4 Weeks After Vaccination (18-64 Years)	SSA: From Vaccination on Day 1 through 4 Weeks after Vaccination	An adverse event (AE) was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious AEs. An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure.
SSA: Percentage of Participants Reporting Adverse Events From Vaccination Through 4 Weeks After Vaccination (>=65 Years)	SSA: From Vaccination on Day 1 through 4 Weeks after Vaccination	An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious AEs. An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure.
SSA: Percentage of Participants Reporting Serious Adverse Events (SAEs) From Vaccination Through 6 Months After Vaccination (18-64 Years)	SSA: From Vaccination on Day 1 through 6 Months after Vaccination	An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event.
SSA: Percentage of Participants Reporting SAEs From Vaccination Through 6 Months After Vaccination (>=65 Years)	SSA: From Vaccination on Day 1 through 6 Months after Vaccination	An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event.
SSA: Percentage of Participants With Abnormal Serum Troponin 1 Laboratory Values at 2 Days After Vaccination (18-64 Years)	SSA: 2 Days after Vaccination	An abnormal troponin 1 result was defined as any troponin 1 level \>=0.30 nanogram per milliliter.
SSA: Percentage of Participants With Abnormal Serum Troponin 1 Laboratory Values at 2 Days After Vaccination (>=65 Years)	SSA: 2 Days after Vaccination	An abnormal troponin 1 result was defined as any troponin 1 level \>=0.30 nanogram per milliliter.
SSA: Percentage of Participants With Abnormal Serum Troponin 1 Laboratory Values at 1 Week After Vaccination (18-64 Years)	SSA: 1 Week After Vaccination	An abnormal troponin 1 result was defined as any troponin 1 level \>=0.30 nanogram per milliliter.
SSA: Percentage of Participants With Abnormal Serum Troponin 1 Laboratory Values at 1 Week After Vaccination (>=65 Years)	SSA: 1 Week After Vaccination	An abnormal troponin 1 result was defined as any troponin 1 level \>=0.30 nanogram per milliliter.
SSA: Percentage of Participants With New Electrocardiogram (ECG) Abnormalities at 2 Days After Vaccination (18-64 Years)	SSA: 2 Days after Vaccination	An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: sustained atrial or ventricular arrhythmias, second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.
SSA: Percentage of Participants With New ECG Abnormalities at 2 Days After Vaccination (>=65 Years)	SSA: 2 Days after Vaccination	An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: sustained atrial or ventricular arrhythmias, second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.
SSA: Percentage of Participants With New ECG Abnormalities at 1 Week After Vaccination (18-64 Years)	SSA: 1 Week after Vaccination	An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: sustained atrial or ventricular arrhythmias, second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.
SSA: Percentage of Participants With New ECG Abnormalities at 1 Week After Vaccination (>=65 Years)	SSA: 1 Week after Vaccination	An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: sustained atrial or ventricular arrhythmias, second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.
SSB: Percentage of Participants With Abnormal Serum Troponin 1 Laboratory Values at 2 Days After Vaccination (18- 64 Years)	SSB: 2 Days after Vaccination	An abnormal troponin 1 result was defined as any troponin 1 level \>=0.30 nanogram per milliliter.
SSB: Percentage of Participants With Abnormal Serum Troponin 1 Laboratory Values at 1 Week After Vaccination (18- 64 Years)	SSB: 1 Week after Vaccination	An abnormal troponin 1 result was defined as any troponin 1 level \>=0.30 nanogram per milliliter.
SSB: Percentage of Participants With New ECG Abnormalities at 2 Days After Vaccination (18- 64 Years)	SSB: 2 Days after Vaccination	An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: sustained atrial or ventricular arrhythmias, second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.
SSB: Percentage of Participants With New ECG Abnormalities at 1 Week After Vaccination (18- 64 Years)	SSB: 1 Week after Vaccination	An ECG abnormality was defined as any new abnormality that, as judged by a cardiologist, was consistent with probable or possible myocarditis or pericarditis, including: sustained atrial or ventricular arrhythmias, second-degree Mobitz Type II or worse atrioventricular block, new bundle branch block and diffuse ST-segment elevation or PR-segment inversion, compatible with pericarditis.
SSB: Percentage of Participants With Local Reactions up to 7 Days Following Vaccination (18- 64 Years)	SSB: From Day 1 to Day 7 after Vaccination	Local reactions included pain at the injection site, redness and swelling and were recorded by participants in an electronic diary. Redness and swelling were measured and recorded in measuring device units, where 1 measuring device unit=0.5 cm. Redness and swelling were graded as mild (Grade 1): \>2.0 cm to 5.0 cm; moderate (Grade 2): \>5.0 cm to 10.0 cm; severe (Grade 3): \>10 cm; potentially life-threatening (Grade 4): necrosis or exfoliative dermatitis. Pain at injection site was graded as mild (Grade 1): did not interfere with activity; moderate (Grade 2): interfered with activity; severe (Grade 3): prevented daily activity and potentially life-threatening (Grade 4): emergency room visit or hospitalization for severe pain. Grade 4 reactions were classified by the investigator or medically qualified person. Percentage of participants with any local reactions were reported in this outcome measure.
SSB: Percentage of Participants With Systemic Events up to 7 Days Following Vaccination (18- 64 Years)	SSB: From Day 1 to Day 7 after Vaccination	Systemic events included fever, vomiting, diarrhea, headache, fatigue, chills, new or worsened muscle pain and new or worsened joint pain. Events were recorded by participants in an electronic diary. Fever defined as oral temperature \>=38.0 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. Vomiting graded as: G1: 1-2 times in 24 h; G2: \>2 times in 24h; G3: required IV hydration. Diarrhea graded as: G1: 2-3 loose stools in 24h; G2: 4-5 loose stools in 24h; G3: 6 or more loose stools in 24h. Headache, fatigue, chills, new/worsened muscle pain and new/worsened joint pain: G1: didn't interfere with activity; G2: some interference with activity; G3: prevented daily routine activity. For all systemic events except fever, Grade 4=emergency room visit or hospitalization. Grade 4 events were classified by the investigator. Percentage of participants with any systemic events were reported in this outcome measure.
SSB: Percentage of Participants Reporting AEs From Vaccination Through 4 Weeks After Vaccination (18- 64 Years)	SSB: From Vaccination on Day 1 through 4 Weeks after Vaccination	An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs included both serious and all non-serious AEs. An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event. Only AEs collected by non-systematic assessment (excluding local reactions and systematic events) were included in this outcome measure.
SSB: Percentage of Participants Reporting SAEs From Vaccination Through 6 Months After Vaccination (18- 64 Years)	SSB: From Vaccination on Day 1 through 6 Months after Vaccination	An SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect and was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic and other important medical event.

Secondary Outcome Measures

Name	Time	Method
SSA: Geometric Mean Titers (GMTs) of Strain-Specific Hemagglutination Inhibition (HAI) Before Vaccination and at 4 Weeks After Vaccination (18- 64 Years)	SSA: Before Vaccination and 4 Weeks after Vaccination	GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations 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. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.
SSA: GMTs of Strain-Specific HAI Before Vaccination and at 4 Weeks After Vaccination (>=65 Years)	SSA: Before Vaccination and 4 Weeks after Vaccination	GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.
SSA: Geometric Mean Fold Rise (GMFRs) of Strain-Specific HAI From Before Vaccination to 4 Weeks After Vaccination (18- 64 Years)	SSA: Before Vaccination to 4 Weeks after Vaccination	GMFRs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ. When pre-vaccination assay results were lower than the LLOQ and the post-vaccination results were greater than or equal to the LLOQ, the pre-vaccination assay results were set to LLOQ for the GMFR calculation. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.
SSA: GMFRs of Strain-Specific HAI From Before Vaccination to 4 Weeks After Vaccination (>=65 Years)	SSA: Before Vaccination to 4 Weeks after Vaccination	GMFRs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ. When pre-vaccination assay results were lower than the LLOQ and the post-vaccination results were greater than or equal to the LLOQ, the pre-vaccination assay results were set to LLOQ for the GMFR calculation. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.
SSA: Percentage of Participants Achieving HAI Seroconversion for Each Strain at 4 Weeks After Vaccination (18- 64 Years)	SSA: 4 Weeks after Vaccination	Seroconversion was defined as an HAI titer \<1:10 prior to vaccination and \>=1:40 at the time point of interest, or an HAI titer of \>=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.
SSA: Percentage of Participants Achieving HAI Seroconversion for Each Strain at 4 Weeks After Vaccination (>=65 Years)	SSA: 4 Weeks after Vaccination	Seroconversion was defined as an HAI titer \<1:10 prior to vaccination and \>=1:40 at the time point of interest, or an HAI titer of \>=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.
SSA: Percentage of Participants With Strain Specific HAI Titers Greater Than or Equal to (>=) 1:40 Before Vaccination and at 4 Weeks After Vaccination (18- 64 Years)	SSA: Before Vaccination and at 4 Weeks after Vaccination	Percentage of participants with HAI titer \>=1:40 for each strain before vaccination and 4 weeks after vaccination is presented in this outcome measure. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.
SSA: Percentage of Participants With Strain Specific HAI Titers >= 1:40 Before Vaccination and at 4 Weeks After Vaccination (>=65 Years)	SSA: Before Vaccination and at 4 Weeks After Vaccination	Percentage of participants with HAI titer \>=1:40 for each strain before vaccination and 4 weeks after vaccination is presented in this outcome measure. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria and B/Phuket.
SSA: Percentage of Participants Achieving HAI Seroconversion for All Strains at 4 Weeks After Vaccination (18- 64 Years)	SSA: 4 Weeks after Vaccination	Seroconversion was defined as an HAI titer \<1:10 prior to vaccination and \>=1:40 at the time point of interest, or an HAI titer of \>=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported combined for all strains (A/Wisconsin, A/Darwin, B/Austria and B/Phuket).
SSA: Percentage of Participants Achieving HAI Seroconversion for All Strains at 4 Weeks After Vaccination (>=65 Years)	SSA: 4 Weeks after Vaccination	Seroconversion was defined as an HAI titer \<1:10 prior to vaccination and \>=1:40 at the time point of interest, or an HAI titer of \>=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported combined for all strains (A/Wisconsin, A/Darwin, B/Austria and B/Phuket).
SSA: Percentage of Participants With HAI Titers >= 1.40 for All Strain at 4 Weeks After Vaccination (18- 64 Years)	SSA: 4 Weeks after Vaccination	Percentage of participants achieving HAI titers \>= 1:40 for each strain at 4 weeks after last vaccination is reported in this outcome measure. Exact 2-sided CI was based on the Clopper and Pearson method. Data is reported combined for all strains (A/Wisconsin, A/Darwin, B/Austria and B/Phuket).
SSA: Percentage of Participants With HAI Titers >= 1.40 for All Strain at 4 Weeks After Vaccination (>=65 Years)	SSA: 4 Weeks after Vaccination	Percentage of participants achieving HAI titers \>= 1:40 for each strain at 4 weeks after last vaccination is reported in this outcome measure. Exact 2-sided CI was based on the Clopper and Pearson method. Data is reported combined for all strains (A/Wisconsin, A/Darwin, B/Austria and B/Phuket).
SSA: GMTs of SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers Before Vaccination and at 4 Weeks After Vaccination (18- 64 Years)	SSA: Before Vaccination and 4 Weeks after Vaccination	GMT of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original \[ancestral strain: Wuhan-Hu-1; USA-WA1/2020\]) neutralizing titers before study vaccination and at 4 week after vaccination were reported in this outcome measure. GMT 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.
SSA: GMTs of SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers Before Vaccination and at 4 Weeks After Vaccination (>=65 Years)	SSA: Before Vaccination and 4 Weeks after Vaccination	GMT of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original \[ancestral strain: Wuhan-Hu-1; USA-WA1/2020\]) neutralizing titers before study vaccination and at 4 week after vaccination was reported in this outcome measure. GMT 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.
SSA: GMFR of SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers Before Vaccination to 4 Weeks After Vaccination (18- 64 Years)	SSA: Before Vaccination to 4 Weeks after Vaccination	GMFR of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original \[ancestral strain: Wuhan-Hu-1; USA-WA1/2020\]) neutralizing titers before study vaccination to 4 week after vaccination was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rise and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.
SSA: GMFR of SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers Before Vaccination to 4 Weeks After Vaccination (>=65 Years)	SSA: Before Vaccination to 4 Weeks after Vaccination	GMFR of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original \[ancestral strain: Wuhan-Hu-1; USA-WA1/2020\]) neutralizing titers before study vaccination to 4 week after vaccination was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rise and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.
SSA: Percentage of Participants With Seroresponse Based on SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers at 4 Weeks After Vaccination (18- 64 Years)	SSA: 4 Weeks after Vaccination	Seroresponse was defined as achieving \>= 4-fold rise from baseline (before study vaccination). If the baseline measurement was below the LLOQ, the postvaccination assay result of \>= 4\*LLOQ was considered a seroresponse. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse Based on SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2-Reference-Strain (ancestral strain (Wuhan-Hu-1; USA-WA1/2020) neutralizing titers at 4 weeks after study vaccination was reported in this outcome measure.
SSA: Percentage of Participants With Seroresponse Based on SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers at 4 Weeks After Vaccination (>=65 Years)	SSA:4 Weeks after Vaccination	Seroresponse was defined as achieving \>= 4-fold rise from baseline (before study vaccination). If the baseline measurement was below the LLOQ, the postvaccination assay result of \>= 4\*LLOQ was considered a seroresponse. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse Based on SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2-Reference-Strain (ancestral strain (Wuhan-Hu-1; USA-WA1/2020) neutralizing titers at 4 weeks after study vaccination was reported in this outcome measure.
SSB: GMTs of Strain-Specific HAI Before Vaccination and at 4 Weeks After Vaccination (18- 64 Years)	SSB: Before Vaccination and 4 Weeks after Vaccination	GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the concentrations and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria, A/Cambodia and B/Phuket.
SSB: GMFR of Strain-Specific HAI From Before Vaccination to 4 Weeks After Vaccination (18- 64 Years)	SSB: Before Vaccination to 4 Weeks after Vaccination	GMFRs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ. When pre-vaccination assay results were lower than the LLOQ and the post-vaccination results were greater than or equal to the LLOQ, the pre-vaccination assay results were set to LLOQ for the GMFR calculation. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria, A/Cambodia and B/Phuket.
SSB: Percentage of Participants Achieving HAI Seroconversion for Each Strain at 4 Weeks After Vaccination (18- 64 Years)	SSB: 4 Weeks after Vaccination	Seroconversion was defined as an HAI titer \<1:10 prior to vaccination and \>=1:40 at the time point of interest, or an HAI titer of \>=1:10 prior to vaccination with a 4-fold rise at the time point of interest. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria,
SSB: Percentage of Participants With Strain Specific HAI Titers >=1:40 Before Vaccination and at 4 Weeks After Vaccination (18- 64 Years)	SSB: Before Vaccination and at 4 Weeks after Vaccination	Percentage of participants with HAI titer \>=1:40 for each strain before vaccination and 4 weeks after vaccination is presented in this outcome measure. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Data is reported for following strains: A/Wisconsin, A/Darwin, B/Austria, A/Cambodia and B/Phuket.
SSB: GMTs of SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers Before Vaccination and at 4 Weeks After Vaccination (18- 64 Years)	SSB: Before Vaccination and at 4 Weeks after Vaccination	GMT of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original \[ancestral strain: Wuhan-Hu-1; USA-WA1/2020\]) neutralizing titers before study vaccination and at 4 week after vaccination was reported in this outcome measure. GMT 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.
SSB: GMFR of SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers From Before Vaccination to 4 Weeks After Vaccination (18- 64 Years)	SSB: 4 Weeks after Vaccination	GMFR of SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2 reference strain (BNT162b2 Original \[ancestral strain: Wuhan-Hu-1; USA-WA1/2020\]) neutralizing titers before study vaccination to 4 week after vaccination was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rise and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5\*LLOQ.
SSB: Percentage of Participants With Seroresponse Based on SARS-CoV-2 Omicron (BA.4/BA.5)- Neutralizing Titers and SARS-CoV-2-Reference-Strain Neutralizing Titers at 4 Weeks After Vaccination (18- 64 Years)	SSB: 4 Weeks after Vaccination	Seroresponse was defined as achieving \>= 4-fold rise from baseline (before study vaccination). If the baseline measurement was below the LLOQ, the postvaccination assay result of \>= 4\*LLOQ was considered a seroresponse. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse Based on SARS-CoV-2 Omicron (BA.4/BA.5)- neutralizing titers and SARS-CoV-2-Reference-Strain (ancestral strain (Wuhan-Hu-1; USA-WA1/2020) neutralizing titers at 4 weeks after study vaccination was reported in this outcome measure.

Trial Locations

Locations (54): DM Clinical Research, Martin Diagnostic Clinic
🇺🇸
Tomball, Texas, United States
North Alabama Research Center
🇺🇸
Athens, Alabama, United States
The Heart Center
🇺🇸
Athens, Alabama, United States
HOPE Research Institute
🇺🇸
Phoenix, Arizona, United States
The Pain Center of Arizona
🇺🇸
Phoenix, Arizona, United States
Orange County Research Center
🇺🇸
Tustin, California, United States
Orange County Heart Institute
🇺🇸
Orange, California, United States
California Research Foundation
🇺🇸
San Diego, California, United States
Proactive Clinical Research,LLC
🇺🇸
Fort Lauderdale, Florida, United States
Finlay Medical Research
🇺🇸
Greenacres City, Florida, United States
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DM Clinical Research, Martin Diagnostic Clinic
🇺🇸Tomball, Texas, United States