To Evaluate the Safety, Tolerability, Efficacy and Immunogenicity of BNT162b2 Boosting Strategies Against COVID-19 in Participants ≥12 Years of Age.

BioNTech SE16,372 enrolled

Overview

Substudy A: The study will evaluate the safety, tolerability, and efficacy of a booster dose of BNT162b2 when administered to participants having previously received 2 doses of BNT162b2 at least 6 months prior to randomization. The study is designed to describe vaccine efficacy of a booster dose of BNT162b2 over time against COVID-19 * At a dose of 30µg (as studied in the Phase 2/3 study C4591001) * In healthy adults 16 years of age and older * The duration of the study for each participant will be up to approximately 12 months. * The study will be conducted in the United States, Brazil and South Africa Substudy B: The study will assess the safety and tolerability of a single dose of BNT162b2 as compared to placebo control, through the potential analysis of serum troponin levels, in participants ≥12 and ≤30 years of age who have received 2 or 3 prior doses of BNT162b2 (30-µg doses) with their last dose at least 4 months (120 days) prior to randomization. * Blood samples will be collected for troponin testing * The duration of the study for each participant will be up to approximately 2 months. * The study will be conducted in the United States, Germany, Poland and South Africa Substudy C: The study will assess the safety, tolerability, and immunogenicity of a booster (third) dose of BNT162b2 at doses of 10 µg or 30 µg in participants who have completed a 2-dose primary series of BNT162b2 (30 µg doses) at least 5 months (150 days) prior to randomization. * In healthy adults 12 years of age and older * The duration of the study for each participant will be up to approximately 12 months. * The study will be conducted in the United States, Germany and South Africa Substudy D: The study will assess the safety, tolerability, and immunogenicity of a 2-dose primary series of BNT162b2 OMI, and as a booster (third, fourth or fifth) dose * Participants in Cohort 1 will have completed a 2-dose primary series of BNT162b2 (30-µg doses), with their last dose 90 to 240 days prior to enrolment * Participants in Cohort 2 will be enrolled from Study C4591001 and C4591031 Substudy A and will have completed a 2-dose primary series and received a single booster (third) dose of BNT162b2, with their last dose 90 to 180 days prior to randomization * Participants in Cohort 3 who are COVID-19 vaccine-naïve and have not experienced COVID-19 will be enrolled to receive 2 doses (primary series) of BNT162b2 OMI, 3 weeks apart, with a dose of BNT162b2 approximately 5 months (150 days) later. If participants do not consent to receive BNT162b2 as a third dose, they will not receive a third dose. No participants should receive BNT162b2 OMI as a third dose. * In healthy adults 18 to 55 years of age * The duration of the study for each participant will be up to approximately 12 months. * The study will be conducted in the United States and South Africa Substudy E: This study will assess the safety, tolerability, and immunogenicity of high-dose BNT162b2 (60 µg), high-dose BNT162b2 OMI (60 µg), and a high-dose combination of BNT162b2 and BNT162b2 OMI at 60 µg (30 µg each), given as a single dose * In healthy adults 18 years of age and older who have received 3 prior doses of BNT162b2 (30 µg) with the most recent dose being 5 to 12 months (150 to 360 days) prior to randomization * The duration of the study for each participant will be approximately 6 months. * The study will be conducted in the United States Substudy F: This study will assess the safety, tolerability, and immunogenicity of high-dose BNT162b2 (60 µg), high-dose BNT162b2 OMI (60 µg), and a high-dose combination of BNT162b2 and BNT162b2 OMI at 60 µg (30 µg each), given as a single dose. * In healthy adults 60 years of age and older who have received 3 prior doses of BNT162b2 (30 µg) with the most recent dose being ≥4 months prior to randomization * The duration of the study for each participant will be approximately 6 months. * The study will be conducted in Israel

Eligibility

Sex: ALLMin age: 12 YearsHealthy volunteers:

Medical Language ↔ Plain English

Substudy A Inclusion Criteria: * Male or female participants ≥16 years of age at Visit 1 (Day 1) who participated in C4591001. * Participants who are willing and able to comply with all scheduled visits, vaccination 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. * Participants who have received 2 prior doses of 30 µg BNT162b2 19-42 days apart, with the second dose being at least 175 days before Visit 1 (Day 1). Exclusion Criteria: * 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. * History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention. * Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19. * 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. * Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study. * Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before study intervention administration, or planned receipt throughout the study. * Prior receipt of any COVID-19 vaccine other than BNT162b2. * Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members. * Receipt of medications intended to prevent COVID-19. * Prior receipt of more than 2 doses of BNT162b2 30 µg. * Participation in other studies involving study intervention within 28 days prior to study entry, other than C4591001, and/or within 28 days of confirmed receipt of BNT162b2 within the study. Substudy B Inclusion Criteria: * Male or female participants 12 to 30 years of age, inclusive, who have received 2 prior doses of 30 µg BNT162b2 19 to 60 days apart, with the second dose being at least at least 4 months (120 days) before Visit 1 (Day 1) * Participants who are willing and able to comply with all scheduled visits, vaccination 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. Exclusion Criteria: * Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behaviour 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 a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention. * Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19. * 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. * Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study. * Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before study intervention administration, or planned receipt throughout the study. * Prior receipt of any COVID-19 vaccine other than BNT162b2. * Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members. * Receipt of medications intended to prevent COVID-19. * Prior receipt of more than 3 doses of BNT162b2 30 µg. * Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation. Substudy C Inclusion Criteria: * Male or female participants ≥12 years of age, inclusive, who have received 2 prior doses of 30 µg BNT162b2 19 to 60 days apart, with the second dose being at least 150 days before Visit 301 (Day 1) * Participants who are willing and able to comply with all scheduled visits, vaccination 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. Exclusion Criteria: * Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behaviour 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 a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention. * Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19. * 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. * Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study. * Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before study intervention administration, or planned receipt throughout the study. * Prior receipt of any COVID-19 vaccine other than BNT162b2. * Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members. * Receipt of medications intended to prevent COVID-19. * Prior receipt of more than 2 doses of BNT162b2 30 µg. * Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation. Substudy D Inclusion Criteria: * Male or female participants 18 to 55 years of age inclusive * Participants who are willing and able to comply with all scheduled visits, vaccination 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. * Cohort 2: Participants who provided a serum sample at Visit 3 in Study C4591001, with Visit 3 occurring within the protocol-specified window. * Capable of giving signed informed consent * Cohort 1: Participants who have received 2 prior doses of 30 µg BNT162b2, with the second dose being 90 to 240 days before Visit 401 (Day 1) or Cohort 2: Participants who have received 3 prior doses of 30 µg BNT162b2, with the third dose being 90 to 180 days before Visit 401 (Day 1). Exclusion Criteria: * 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. * History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention. * Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19. * 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. * Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study. * Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before study intervention administration, or planned receipt throughout the study. * Cohorts 1 and 2: prior receipt of any COVID-19 vaccine other than BNT162b2. * Cohort 3 only: prior receipt of any COVID-19 vaccine. * Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members. * Receipt of medications intended to prevent COVID 19. * Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation. Substudy E Inclusion Criteria: * Groups 1-6: Male or female participants \>55 years of age * Groups 7-9: Male or female participants 18 to 55 years of age * Participants who are willing and able to comply with all scheduled visits, vaccination 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. * Participants who have received 3 prior doses of 30 µg BNT162b2, with the third dose being 5 to 12 months (150 to 360 days) before Visit 601 (Day 1). * Groups 7 to 9 (sentinel participants): Screening troponin levels must be within normal range prior to randomization. Exclusion Criteria: * 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. * History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention. * Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19. * 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. * Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study. * Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before study intervention administration, or planned receipt throughout the study. * Prior receipt of any COVID-19 vaccine other than BNT162b2. * Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members. * Receipt of medications intended to prevent COVID-19. * Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation. Substudy F Inclusion Criteria: * Male or female participants ≥60 years of age * Participants who are willing and able to comply with all scheduled visits, vaccination 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. * Participants who have received 3 prior doses of 30 µg BNT162b2, with the third dose being ≥4 months before Visit 701 (Day 1). Exclusion Criteria: * 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. * History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any component of the study intervention. * Previous clinical (based on COVID-19 symptoms/signs alone, if a SARS-CoV-2 NAAT result was not available) or microbiological (based on COVID-19 symptoms/signs and a positive SARS-CoV-2 NAAT result) diagnosis of COVID-19. * 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. * Individuals who receive treatment with radiotherapy or immunosuppressive therapy, including cytotoxic agents or systemic corticosteroids, eg, for cancer or an autoimmune disease, or planned receipt throughout the study. * Receipt of blood/plasma products, immunoglobulin, or monoclonal antibodies, from 60 days before study intervention administration, or receipt of any passive antibody therapy specific to COVID-19, from 90 days before study intervention administration, or planned receipt throughout the study. * Prior receipt of any COVID-19 vaccine other than BNT162b2. * Investigator site staff or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members. * Receipt of medications intended to prevent COVID-19. * Participation in other studies involving study intervention within 28 days prior to study entry through and including 28 days after the last dose of study intervention, with the exception of non-Pfizer interventional studies for prevention of COVID-19, which are prohibited throughout study participation.

Outcomes

Primary Outcomes

SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population

Occurrences (number of cases) of first COVID-19 infection in participants after booster dose per 1000 person-year, without past SARS-CoV-2 infection at interim analysis were reported in this outcome measure.

Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year [PY]) for BNT162b2 was 0.823 and for Placebo was 0.792

SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population

Occurrences (number of cases) of first COVID-19 infection in participants after booster dose with and without past SARS-CoV-2 infection at interim analysis were reported in this outcome measure.

Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 0.871 and for Placebo was 0.835

SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population

Occurrences (number of cases) of first COVID-19 infection in participants after booster dose without past SARS-CoV-2 infection at final analysis were reported in this outcome measure.

Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 1.098 and for Placebo was 0.932

SSA: Occurrence of First COVID-19 Infection After Booster Dose Per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population

Occurrences (number of cases) of first COVID-19 infection in participants after booster dose with and without past SARS-CoV-2 infection at final analysis were reported in this outcome measure.

Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 1.173 and for Placebo was 0.989

SSA: Percentage of Participants Reporting Adverse Events

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.

Time frame: From booster dose (Day 1) to 1 month after booster dose

SSA: Percentage of Participants Reporting Serious Adverse Events (SAE)

An SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect; or that was considered as an important medical event.

Time frame: BNT162b2 30 mcg, Placebo then BNT162b2 30 mcg: From BNT162b2 dose to 6 months after BNT162b2 dose; Placebo: From placebo dose to unblinding for original placebo participants. Median blinded follow-up period for Placebo group=2.8 months

SSB: Percentage of Participants With Elevated Troponin I Level Pre-Dose; Vaccination 1

Percentage of participants with elevated troponin I levels before administration of Vaccination 1 were reported in this outcome measure.

Time frame: Pre-dose on Day 1 (Vaccination 1)

SSB: Percentage of Participants With Elevated Troponin I Level Within 5 Days After Vaccination 1

Percentage of participants with elevated troponin I levels within 5 days after administration of Vaccination 1 were reported in this outcome measure.

Time frame: Within 5 days after Vaccination 1

SSB: Percentage of Participants With Elevated Troponin I Level Pre-Vaccination 2 (1 Month After Vaccination 1)

Percentage of participants with elevated troponin I levels pre vaccination 2 were reported in this outcome measure.

Time frame: Pre-Vaccination 2 (1 month after Vaccination 1)

SSB: Percentage of Participants With Elevated Troponin I Level Within 5 Days After Vaccination 2

Percentage of participants with elevated troponin I levels within 5 days after administration of Vaccination 2 were reported in this outcome measure.

Time frame: Within 5 days after vaccination 2

SSB: Percentage of Participants With Elevated Troponin I Level 1 Month After Vaccination 2

Percentage of participants with elevated troponin I levels within 1 month after administration of Vaccination 2 were reported in this outcome measure.

Time frame: 1 month after Vaccination 2

SSB: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1

Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 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 \[swelling\] or 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 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 1 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.

Time frame: Day 1 up to Day 7 after Vaccination 1

SSB: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2

Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 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 \[swelling\] or 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 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 2 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.

Time frame: Day 1 up to Day 7 after Vaccination 2

SSB: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1

Systemic events were recorded in e-diary. Fever: oral temperature greater than or equal to (\>=) 38.0 degree Celsius (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 new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 hours (h), moderate: \>2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.

Time frame: Day 1 up to Day 7 after Vaccination 1

SSB: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2

Time frame: Day 1 up to Day 7 after Vaccination 2

SSB: Percentage of Participants Reporting Adverse Events (AEs) 1 Month After Vaccination 1

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. Percentage of participants reporting AEs within 1 month after Vaccination 1 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.

Time frame: Vaccination 1 up to 1 Month After Vaccination 1

SSB: Percentage of Participants Reporting Adverse Events (AEs) 1 Month After Vaccination 2

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. Percentage of participants reporting AEs within 1 month after Vaccination 2 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.

Time frame: Vaccination 2 up to 1 month after Vaccination 2

SSB: Percentage of Participants Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 1

An SAE was defined as any untoward medical occurrence that at any dose 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. Exact 2-sided 95% CI was based on the Clopper and Pearson method.

Time frame: Vaccination 1 up to 1 month after Vaccination 1

SSB: Percentage of Participants Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 2

Time frame: Vaccination 2 up to 1 month after Vaccination 2

SSC: Percentage of Participants With Local Reactions Within 7 Days After Booster Dose

Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 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 \[swelling\] or 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 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after the booster (third) dose and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.

Time frame: Day 1 up to Day 7 after the booster dose

SSC: Percentage of Participants With Systemic Events Within 7 Days After Booster Dose

Systemic events were recorded in e-diary. Fever: oral temperature greater than or equal to (\>=) 38.0 degree Celsius (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 new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 hours (h), moderate: \>2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24 h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.

Time frame: Day 1 up to Day 7 after the booster dose

SSC: Percentage of Participants Reporting Adverse Events From Booster Dose Through 1 Month After Booster Dose

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. Percentage of participants reporting AEs from booster (third) dose up to 1 month after booster (third) dose were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.

Time frame: From booster dose (Day 1) up to 1 month after booster dose

SSC: Percentage of Participants Reporting Serious Adverse Events From Booster Dose Through 6 Months After Booster Dose

Time frame: From booster dose (Day 1) up to 6 months after booster dose

SSC: Geometric Mean Titers (GMT) of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Baseline

GMT of SARS-CoV-2 reference-strain-neutralizing titers at baseline (before the booster dose) was reported in this outcome measure. 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).

Time frame: At baseline (pre-dose)

SSC: GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at 1 Month After the Booster Dose

GMT of SARS-CoV-2 reference-strain-neutralizing titers at 1 month after the booster dose was reported in this outcome measure. 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).

Time frame: 1 month after the booster dose

SSC: Geometric Mean Fold-Rise (GMFR) of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Baseline to 1 Month After the Booster Dose

GMFR of SARS-CoV-2 reference-strain-neutralizing titers from baseline to 1 month after the booster dose received in this sub-study was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).

Time frame: From baseline to 1 month after the booster dose

SSC: Percentage of Participants With Seroresponse to Reference-Strain at 1 Month After the Booster Dose

Seroresponse was defined as achieving \>= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of \>= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 1 month after the booster dose was reported in this outcome measure.

Time frame: 1 month after the booster dose

SSD: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1

Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu=0.5 centimeter (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 \[swelling\] or necrosis or exfoliative dermatitis \[redness\]). Pain at injection (inj) 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/hospitalization for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 1 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.

Time frame: Day 1 up to Day 7 after Vaccination 1

SSD: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2

Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (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 \[swelling\] or 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 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 2 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.

Time frame: Day 1 up to Day 7 after Vaccination 2

SSD: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 3

Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (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 \[swelling\] or 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 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after Vaccination 3 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.

Time frame: Day 1 up to Day 7 after Vaccination 3

SSD: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1

Systemic events were recorded in e-diary. Fever: oral temperature \>= 38.0 deg C, 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 new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 h, moderate: \>2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.

Time frame: Day 1 up to Day 7 after Vaccination 1

SSD: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2

Time frame: Day 1 up to Day 7 after Vaccination 2

SSD: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 3

Systemic events were recorded in e-diary. Fever: oral temperature \>= 38.0 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 new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalization). Vomiting: mild: 1-2 times in 24 hours (h), moderate: \>2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.

Time frame: Day 1 up to Day 7 after Vaccination 3

SSD: Percentage of Participants Reporting Adverse Events (AEs) From First Study Vaccination (Day 1) Through 1 Month After Last Study Vaccination: Cohort 1

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. Percentage of participants reporting AEs from first study vaccination (Day 1) up to 1 month after last study vaccination were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.

Time frame: From Day 1 up to 1 month after last study vaccination

SSD: Percentage of Participants Reporting Adverse Events (AEs) From First Study Vaccination (Day 1) Through 1 Month After Vaccination 1: Cohort 2

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. Percentage of participants reporting AEs from first study vaccination (Day 1) up to 1 month after Vaccination 1 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.

Time frame: From first study vaccination (Day 1) up to 1 month after Vaccination 1

SSD: Percentage of Participants Reporting Adverse Events (AEs) From Second Study Vaccination Through 1 Month After Second Study Vaccination: Cohort 2

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. Percentage of participants reporting AEs from Vaccination 2 up to 1 month after Vaccination 2 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.

Time frame: From Vaccination 2 up to 1 month after Vaccination 2

SSD: Percentage of Participants Reporting Adverse Events (AEs) From First Study Vaccination (Day 1) Through 1 Month After Second Study Vaccination: 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. Percentage of participants reporting AEs from first study vaccination (Day 1) up to 1 month after Vaccination 2 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.

Time frame: From first study vaccination (Day 1) up to 1 month after Vaccination 2

SSD: Percentage of Participants Reporting Adverse Events (AEs) From Third Study Vaccination Through 1 Month After Third Study Vaccination: 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. Percentage of participants reporting AEs from Vaccination 3 up to 1 month after Vaccination 3 were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.

Time frame: From Vaccination 3 up to 1 month after Vaccination 3

SSD: Percentage of Participants Reporting Serious Adverse Events (SAEs) From First Study Vaccination (Day 1) Through 6 Months After Last Study Vaccination: Cohort 1 and Cohort 3

A SAE was defined as any untoward medical occurrence that at any dose 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. Exact 2-sided 95% CI was based on the Clopper and Pearson method.

Time frame: From first study vaccination (Day 1) up to 6 months after last study vaccination

SSD: Percentage of Participants Reporting SAEs From First Study Vaccination (Day 1) Through 6 Months After Vaccination 1 (For Participants Who Received 1 Dose Only) and up to Vaccination 2 (For Participants Who Received 2 Doses): Cohort 2

Time frame: From vaccination 1 (Day 1) up to 6 months after vaccination 1 (participants received 1 dose only); From vaccination 1 up to before vaccination 2 (participants received 2 doses)

SSD: Percentage of Participants Reporting Serious Adverse Events (SAEs) From First Study Vaccination Through 6 Months After Vaccination 2: Cohort 2

Time frame: From first study vaccination (Day 1) up to 6 months after vaccination 2

SSD: GMR Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers 1 Month After First Study Vaccination: Comparison Between Cohort 2 Group 3 and Group 4

GMR was calculated based on GMT levels of SSD: Cohort 2: Group 3 and SSD: Cohort 2: Group 4 and reported in statistical analysis section below. GMT of SARS-CoV-2 Omicron strain-neutralizing titers and reported in statistical analysis. GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers at 1 month after first study vaccination was reported in this outcome measure. 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).

Time frame: 1 month after Vaccination 1

SSD: Percentage of Participants With Seroresponse to the SARS-CoV-2 Omicron BA.1 Strain at 1 Month After First Study Vaccination: Comparison Between Cohort 2 Group 3 and Group 4

Seroresponse: achieving \>= 4-fold rise from baseline (before study vaccination). If baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of \>= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse 1 month after first study vaccination was reported in this outcome measure.

Time frame: 1 month after Vaccination 1

SSD: GMR Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers 1 Month After First Study Vaccination: Comparison Between Cohort 1 Group 1 and Group 2b

GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers at 1 month after first study vaccination was reported in this outcome measure. 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).

Time frame: 1 month after Vaccination 1

SSD: GMR Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers: Comparison Between 1 Month After Second Study Vaccination for Cohort 1 Group 2 and 1 Month After First Study Vaccination for Cohort 1 Group 2b

GMR was calculated based on GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers at 1 month after Vaccination 2 for Group 2 and 1 month after Vaccination 1 for Group 2b was reported. GMTs and corresponding 2-sided CIs were calculated by exponentiating mean logarithm of titers and corresponding CIs (based on Student's t distribution).

Time frame: For Cohort 1 Group 2b:1 month after Vaccination 1; for Cohort 1 Group 2: 1 month after Vaccination 2

Percentage of Participants With Seroresponse to the SARS-CoV-2 Omicron BA.1 Strain at 1 Month After First Study Vaccination: Comparison Between Cohort 1 Group 1 and Group 2b

Seroresponse: achieving \>= 4-fold rise from baseline (before study vaccination). If baseline measurement is below lower limit of quantification (LLOQ), the postvaccination measure of \>= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of participants achieving seroresponse 1 month after first study vaccination was reported in this outcome measure.

Time frame: 1 month after Vaccination 1

SSD: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron BA.1 Strain at 1 Month After Vaccination 2: Comparison Between 1 Month After Vaccination 2 for Cohort 1 Group 2 and 1 Month After Vaccination 1 for Cohort 1 Group 2b

Seroresponse: achieving \>= 4-fold rise from baseline (before study vaccination). If baseline measurement is below LLOQ, postvaccination measure of \>= 4 × LLOQ is considered seroresponse. Exact 2-sided CI, based on Clopper and Pearson method was used. Percentage of participants achieving seroresponse 1 month after second study vaccination for Group 2 and 1 month after study vaccination for Group 2b was reported in this outcome measure.

Time frame: For Cohort 1 Group 2b:1 month after Vaccination 1; for Cohort 1 Group 2: 1 month after Vaccination 2

SSD: GMR Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers 1 Month After Second Study Vaccination: Cohort 3

GMR calculated based on GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMR comparison between GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers of participants of SSD Cohort 3: Group 5 to GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers of participants of study C4591001 (NCT04368728) Phase 3 BNT162b2 single arm 18-55 years of age, at 1 month after vaccination 2 was reported. GMTs and corresponding 2-sided CIs were calculated by exponentiating mean logarithm of titers and corresponding CIs (student's t distribution).

Time frame: 1 month after Vaccination 2

SSD: Percentage of Participants With Seroresponse to the SARS-CoV-2 Omicron BA.1 Strain at 1 Month After Second Study Vaccination: Cohort 3

EIP:eligible participants received 2 doses of study drug as randomized with Dose2 received within 19-42 days after Dose1 (SSD Cohort 3:Group 5), had valid determinate immunogenicity result from blood sample collected within 28-42 days after 2nd study vaccination, had no other important protocol deviations as determined by clinician. Data of eligible participants from Study C4591001 Phase 3 BNT162b2 single arm 18-55 years was included for comparison.'N'=participants evaluable for outcome measure.

Time frame: 1 month after Vaccination 2

SSE: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination

Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 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 \[swelling\] or necrosis/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/hospitalization for severe pain). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions within 7 days after study vaccination and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.

Time frame: Day 1 up to Day 7 after study vaccination

SSE: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination

Systemic events were recorded in e-diary. Fever: oral temperature greater than or equal to 38.0 deg C and categorized as \>=38.0-38.4 deg C, \>38.4-38.9 deg C, \>38.9-40.0 deg C \& \>40.0 deg C. Fatigue, headache, chills, muscle pain and joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit or hospitalization). Vomiting: mild: 1-2 times in 24 h, moderate: \> 2 times in 24h, severe: required intravenous hydration and Grade 4: ER or hospitalization for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit or hospitalization for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method.

Time frame: Day 1 up to Day 7 after study vaccination

SSE: Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination

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. Percentage of participants reporting AEs within 1 month after study vaccination were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.

Time frame: From study vaccination up to 1 Month after study vaccination

SSE: Percentage of Participants Reporting Serious Adverse Events (SAEs) Within 6 Month After Study Vaccination

Time frame: From study vaccination up to 6 Months after study vaccination

SSE: Percentage of Participants With Elevated Troponin I Levels Before the Study Vaccination- 18 to 55 Years of Age

Percentage of participants with elevated troponin I levels before study vaccination were reported in this outcome measure.

Time frame: Before study vaccination (pre-dose)

SSE: Percentage of Participants With Elevated Troponin I Levels 3 Days After Study Vaccination- 18 to 55 Years of Age

Percentage of participants with elevated troponin I levels before study vaccination were reported in this outcome measure.

Time frame: 3 days after study vaccination

SSE: Geometric Mean Ratio (GMR) Based on Geometric Mean Titers of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers 1 Month After Study Vaccination

GMR calculated based on GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers at 1 month after the study vaccination was reported in this outcome measure. 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).

Time frame: 1 month after study vaccination

SSE: Percentage of Participants With Seroresponse to the SARS-CoV-2 Omicron BA.1 Strain at 1 Month After Study Vaccination

Seroresponse was defined as achieving \>= 4-fold rise from baseline (before study vaccination). If baseline measurement is below lower limit of quantification (LLOQ), postvaccination measure of \>= 4 × LLOQ is considered seroresponse. Exact 2-sided CI, based on Clopper and Pearson method was used. Percentage of participants achieving seroresponse at 1 month was reported in this outcome measure.

Time frame: 1 month after study vaccination

SSF: Geometric Mean Titer (GMTs) of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers Before Vaccination

GMT of SARS-CoV-2 Omicron BA.1 strain neutralizing titers before vaccination was reported in this outcome measure. 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).

Time frame: Before vaccination (pre-dose)

SSF: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination

Local reactions were recorded by participants in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 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 (emergency room \[ER\] visit or hospitalization for severe pain). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (necrosis \[swelling\] or necrosis/exfoliative dermatitis \[redness\]). Grade 4 were classified by investigator or medically qualified person. Percentage of participants reporting local reactions after study vaccination and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented.

Time frame: Day 1 up to Day 7 after the study vaccination

SSF: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination

Time frame: Day 1 up to Day 7 after the study vaccination

SSF: Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination

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. Percentage of participants reporting AEs within 1 month after study vaccination were reported in this outcome measure. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this outcome measure.

Time frame: From study vaccination up to 1 Month after study vaccination

SSF: Percentage of Participants Reporting Serious Adverse Events (SAEs) Within 6 Months After Study Vaccination

Time frame: From study vaccination up to 6 Months after study vaccination

SSF: GMTs of SARS-CoV-2 Reference-Strain-Neutralizing Titers Before Vaccination

GMT of SARS-CoV-2 reference-strain-neutralizing titers before vaccination was reported in this outcome measure. 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).

Time frame: Before vaccination (pre-dose)

SSF: GMTs of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers Before Vaccination

GMT of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers before vaccination was reported in this outcome measure. 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).

Time frame: Before vaccination (pre-dose)

SSF: Geometric Mean Ratio (GMR) Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Day 7

GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at Day 7 were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% 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.

Time frame: Day 7 (7 days after vaccination)

SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Day 7

GMR was calculated based on the GMT of SARS-CoV-2 Omicron reference strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 reference strain neutralizing titers at Day 7 were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% 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.

Time frame: Day 7 (7 days after vaccination)

SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers at Day 7

GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at Day 7 were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% 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.

Time frame: Day 7 (7 days after vaccination)

SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Month 1

GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at 1 month were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% 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.

Time frame: Month 1 (1 month after vaccination)

SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Month 1

GMR was calculated based on the GMT of SARS-CoV-2 Omicron reference strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 reference strain neutralizing titers at 1 month were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% 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.

Time frame: Month 1 (1 month after vaccination)

SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 1

GMR was calculated based on the GMT of SARS-CoV-2 Omicron reference strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at 1 month were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% 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.

Time frame: Month 1 (1 month after vaccination)

SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Month 3

GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at 3 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% 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.

Time frame: Month 3 (3 month after vaccination)

SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Month 3

GMR was calculated based on the GMT of SARS-CoV-2 Omicron reference strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 reference strain neutralizing titers at 3 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% 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.

Time frame: Month 3 (3 month after vaccination)

SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 3

GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at 3 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% 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.

Time frame: Month 3 (3 month after vaccination)

SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Month 6

GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at 6 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% 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.

Time frame: Month 6 (6 month after vaccination)

SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Month 6

GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 reference strain neutralizing titers at 6 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% 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.

Time frame: Month 6 (6 months after vaccination)

SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 6

GMR was calculated based on the GMT of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers and reported in statistical analysis. GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at 6 months were reported in this outcome measure in descriptive data section. GMTs and the 2-sided 95% 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.

Time frame: Month 6 (6 months after vaccination)

SSF: Geometric Mean Fold-Rise (GMFR) of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 7 Days After Vaccination

GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to Day 7 was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).

Time frame: From before the study vaccination to Day 7 (7 days after vaccination)

SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 7 Days After Vaccination

GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to Day 7 was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).

Time frame: From before the study vaccination to Day 7 (7 days after vaccination)

SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 7 Days After Vaccination

GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to Day 7 was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).

Time frame: From before the study vaccination to Day 7 (7 days after vaccination)

SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination

GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to 1 month was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).

Time frame: From before the study vaccination to 1 month after vaccination

SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination

GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 1 month was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).

Time frame: From before the study vaccination to 1 month after vaccination

SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination

GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to 1 month was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).

Time frame: From before the study vaccination to 1 month after vaccination

SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination

GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to 3 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).

Time frame: From before the study vaccination to 3 months after vaccination

SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination

GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 3 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).

Time frame: From before the study vaccination to 3 months after vaccination

SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination

GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to 3 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).

Time frame: From before the study vaccination to 3 months after vaccination

SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination

GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to 6 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).

Time frame: From before the study vaccination to 6 months after vaccination

SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination

GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 6 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).

Time frame: From before the study vaccination to 6 months after vaccination

SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination

GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to 6 months was reported in this outcome measure. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution).

Time frame: From before the study vaccination to 6 months after vaccination

SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Day 7

Time frame: Day 7 (7 days after vaccination)

SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Day 7

Time frame: Day 7 (7 days after vaccination)

SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Day 7

Time frame: Day 7 (7 days after vaccination)

SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 1

Time frame: Month 1 (1 month after vaccination)

SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 1

Time frame: Month 1 (1 month after vaccination)

SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 1

Time frame: Month 1 (1 month after vaccination)

SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 3

Time frame: Month 3 (3 months after vaccination)

SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 3

Time frame: Month 3 (3 months after vaccination)

SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 3

Time frame: Month 3 (3 months after vaccination)

SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 6

Time frame: Month 6 (6 months after vaccination)

SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 6

Time frame: Month 6 (6 months after vaccination)

SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 6

Time frame: Month 6 (6 months after vaccination)

Secondary Outcomes

SSA: Occurrence of First Severe COVID-19 Infection (FDA Definition) Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection: Evaluable Efficacy Population

Occurrence (number of cases) of first severe COVID-19 infection based on FDA definition after booster dose without past SARS-CoV-2 infection is reported. FDA definition: confirmed COVID-19 and presence of at least 1 of the following: 1) clinical signs at rest indicative of severe systemic illness (respiratory rate greater than or equal to \[\>=\]30 breaths per minute, heart rate \>= 125 beats per minute, oxygen saturation less than or equal to \[\<=\]93% on room air at sea level, or Horovitz quotient \<300 mmHg); 2) respiratory failure (needing high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation); 3) evidence of shock (systolic blood pressure \[BP\] \<90 mmHg, diastolic BP \<60 mmHg, or requiring vasopressors); 4) significant acute renal, hepatic, or neurologic dysfunction; 5) admission to an intensive care unit; 6) death.

Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 1.105 and for Placebo was 0.951

SSA: Occurrence of First Severe COVID-19 Infection (FDA Definition) Per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection: Evaluable Efficacy Population

Occurrence (number of cases) of first severe COVID-19 infection based on FDA definition after booster dose with and without past SARS-CoV-2 infection is reported. FDA definition: confirmed COVID-19 and presence of at least 1 of the following: 1) clinical signs at rest indicative of severe systemic illness (respiratory rate \>= 30 breaths per minute, heart rate \>= 125 beats per minute, oxygen saturation \<= 93% on room air at sea level, or Horovitz quotient \<300 mm Hg); 2) respiratory failure (defined as needing high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation); 3) evidence of shock (systolic BP \<90 mm Hg, diastolic BP \<60 mm Hg, or requiring vasopressors); 4) significant acute renal, hepatic, or neurologic dysfunction; 5) admission to an intensive care unit; 6) death.

Time frame: From 7 Days after booster vaccination to end of surveillance period, total surveillance time (in 1000 person-year) for BNT162b2 was 1.182 and for Placebo was 1.011

SSA: Occurrence of First Severe COVID-19 Infection (CDC Definition) Per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection

To Evaluate the Safety, Tolerability, Efficacy and Immunogenicity of BNT162b2 Boosting Strategies Against COVID-19 in Participants ≥12 Years of Age.

Overview

Conditions

Interventions

Eligibility

Locations (154)

Outcomes

Primary Outcomes

Secondary Outcomes