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

NCT04955626 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: C45910312021-005197-25
• Study Type: interventional
• Target: 16,372
• Locations: 5 countries
• Sites: 154

Brief Summary

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

Conditions

SARS-CoV-2 Infection; COVID-19

Keywords

COVID-19; Coronavirus; Vaccine; SARS-CoV-2; RNA Vaccine

Outcome Measures

Primary Outcomes (100)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  Day 1 up to Day 7 after Vaccination 1

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

  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.

  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.

  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.

  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.

  Vaccination 1 up to 1 month after Vaccination 1

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

  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.

  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.

  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.

  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.

  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

  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.

  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).

  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).

  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).

  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.

  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.

  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.

  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.

  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.

  Day 1 up to Day 7 after Vaccination 1

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

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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

  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.

  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

  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.

  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).

  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.

  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).

  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).

  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.

  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.

  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).

  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.

  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.

  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.

  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.

  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

  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.

  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.

  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.

  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).

  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.

  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).

  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.

  Day 1 up to Day 7 after the study vaccination

• SSF: 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.

  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.

  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

  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.

  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).

  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).

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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).

  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

  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 on Day 7 was reported in this outcome measure.

  Day 7 (7 days after vaccination)

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

  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 on Day 7 was reported in this outcome measure.

  Day 7 (7 days after vaccination)

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

  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 on Day 7 was reported in this outcome measure.

  Day 7 (7 days after vaccination)

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

  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 was reported in this outcome measure.

  Month 1 (1 month after vaccination)

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

  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 was reported in this outcome measure.

  Month 1 (1 month after vaccination)

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

  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 was reported in this outcome measure.

  Month 1 (1 month after vaccination)

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

  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 3 months was reported in this outcome measure.

  Month 3 (3 months after vaccination)

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

  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 3 months was reported in this outcome measure.

  Month 3 (3 months after vaccination)

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

  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 3 months was reported in this outcome measure.

  Month 3 (3 months after vaccination)

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

  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 6 months was reported in this outcome measure.

  Month 6 (6 months after vaccination)

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

  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 6 months was reported in this outcome measure.

  Month 6 (6 months after vaccination)

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

  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 6 months was reported in this outcome measure.

  Month 6 (6 months after vaccination)

Secondary Outcomes (11)

• 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

  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

  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

  From 7 Days after booster vaccination

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

  From 7 Days after booster vaccination

• SSC: GMTs of SARS-CoV-2 Reference-Strain Neutralizing Titers at Baseline and 7 Days After the Booster Dose

  At baseline and 7 days after the booster dose

Study Arms (4)

10 µg dose

EXPERIMENTAL

1 dose

Biological: BNT162b2

Placebo

PLACEBO COMPARATOR

1 dose

Other: Placebo

30 µg dose

EXPERIMENTAL

1 dose

Biological: BNT162b2; Biological: BNT162b2 OMI; Biological: Combination BNT162b2 and BNT162b2 OMI; Biological: Combination (Bivalent) BNT162b2 and BNT162b2 OMI

60 µg dose

EXPERIMENTAL

1 dose

Biological: BNT162b2; Biological: BNT162b2 OMI; Biological: Combination BNT162b2 and BNT162b2 OMI; Biological: Combination (Bivalent) BNT162b2 and BNT162b2 OMI

Interventions

BNT162b2 BIOLOGICAL

Intramuscular Injection

10 µg dose; 30 µg dose; 60 µg dose

Placebo OTHER

Intramuscular Injection

Placebo

BNT162b2 OMI BIOLOGICAL

Intramuscular Injection

30 µg dose; 60 µg dose

Combination BNT162b2 and BNT162b2 OMI BIOLOGICAL

30-µg (15-µg each) or 60-µg (30-µg each) Site prepared dosing suspension from 1 vial each of diluted BNT162b2 and BNT162b2 OMI Intramuscular Injection

30 µg dose; 60 µg dose

Combination (Bivalent) BNT162b2 and BNT162b2 OMI BIOLOGICAL

30-µg (15-µg each) or 60-µg (30-µg each) Preformulated bivalent mixture (no dilution required) presented in a single vial Intramuscular Injection

30 µg dose; 60 µg dose

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• BioNTech SE: lead
• Pfizer: collaborator

Study Sites (154)

North Alabama Research Center

Athens, Alabama, 35611, United States

Location

Accel Research Sites - Birmingham Clinical Research Unit

Birmingham, Alabama, 35216, United States

Location

Medical Affiliated Research Center

Huntsville, Alabama, 35801, United States

Location

AMR Clinical

Mobile, Alabama, 36608, United States

Location

Johns Hopkins Center for American Indian Health

Chinle, Arizona, 86503, United States

Location

Hope Research Institute

Phoenix, Arizona, 85018, United States

Location

The Pain Center of Arizona

Phoenix, Arizona, 85018, United States

Location

HOPE Research Institute

Phoenix, Arizona, 85023, United States

Location

Alliance for Multispecialty Research, LLC

Tempe, Arizona, 85281, United States

Location

Johns Hopkins Center for American Indian Health

Whiteriver, Arizona, 85941, United States

Location

Whiteriver Indian Hospital- Garrett Building

Whiteriver, Arizona, 85941, United States

Location

Whiteriver Indian Hospital

Whiteriver, Arizona, 85941, United States

Location

Anaheim Clinical Trials, LLC

Anaheim, California, 92801, United States

Location

Collaborative Neuroscience Research, LLC

Long Beach, California, 90806, United States

Location

Collaborative Neuroscience Research, LLC

Los Alamitos, California, 90720, United States

Location

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, 90027, United States

Location

Kaiser Permenente Medical Center Infectious Disease

Los Angeles, California, 90027, United States

Location

Velocity Clinical Research, Los Angeles

Los Angeles, California, 90057, United States

Location

Velocity Clinical Research, North Hollywood

North Hollywood, California, 91606, United States

Location

Kaiser Permanente Oakland

Oakland, California, 94611, United States

Location

Paradigm Clinical Research Centers, Inc

Redding, California, 96001, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

California Research Foundation

San Diego, California, 92123, United States

Location

Kaiser Permanente Santa Clara

Santa Clara, California, 95051, United States

Location

Bayview Research Group, LLC

Valley Village, California, 91607, United States

Location

Diablo Clinical Research, Inc.

Walnut Creek, California, 94598, United States

Location

Lynn Institute of Denver

Aurora, Colorado, 80012, United States

Location

Clinical Research Consulting

Milford, Connecticut, 06460, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Yale-New Haven Hospital

New Haven, Connecticut, 06511, United States

Location

Yale Center for Clinical Investigation

New Haven, Connecticut, 06519, United States

Location

Alliance for Multispecialty Research, LLC

Coral Gables, Florida, 33134, United States

Location

Indago Research & Health Center, Inc

Hialeah, Florida, 33012, United States

Location

Research Centers of America ( Hollywood )

Hollywood, Florida, 33024, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Clinical Neuroscience Solutions, Inc. dba CNS Healthcare

Jacksonville, Florida, 32256, United States

Location

Acevedo Clinical Research Associates

Miami, Florida, 33142, United States

Location

Clinical Neuroscience Solutions, Inc.

Orlando, Florida, 32801, United States

Location

IACT Health

Columbus, Georgia, 31904, United States

Location

Meridian Clinical Research

Savannah, Georgia, 31406, United States

Location

Clinical Research Atlanta

Stockbridge, Georgia, 30281, United States

Location

East-West Medical Research Institute

Honolulu, Hawaii, 96814, United States

Location

Solaris Clinical Research

Meridian, Idaho, 83646, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Velocity Clinical Research, Sioux City

Sioux City, Iowa, 51106, United States

Location

AMR Clinical

Newton, Kansas, 67114, United States

Location

AMR Clinical

Wichita, Kansas, 67207, United States

Location

Kentucky Pediatric/ Adult Research

Bardstown, Kentucky, 40004, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Louisiana State University Health Sciences Shreveport

Shreveport, Louisiana, 71101, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

University of Massachusetts Chan Medical School

Worcester, Massachusetts, 01655, United States

Location

Michigan Center of Medical Research (MICHMER)

Farmington Hills, Michigan, 48334, United States

Location

Velocity Clinical Research, Covington

Gulfport, Mississippi, 39503, United States

Location

Clinical Research Professionals

Chesterfield, Missouri, 63005, United States

Location

Sundance Clinical Research

St Louis, Missouri, 63141, United States

Location

Bozeman Health Deaconess Hospital d/b/a Bozeman Health Clinical Research

Bozeman, Montana, 59715, United States

Location

Bozeman Health Deaconess Hospital

Bozeman, Montana, 59715, United States

Location

Methodist Physicians Clinic/CCT Research

Fremont, Nebraska, 68025, United States

Location

Velocity Clinical Research, Norfolk

Norfolk, Nebraska, 68701, United States

Location

Quality Clinical Research

Omaha, Nebraska, 68114, United States

Location

Velocity Clinical Research, Omaha

Omaha, Nebraska, 68134, United States

Location

Wake Research - Clinical Research Center of Nevada, LLC

Las Vegas, Nevada, 89106, United States

Location

South Jersey Infectious Disease

Somers Point, New Jersey, 08244, United States

Location

IMA Clinical Research Warren

Warren Township, New Jersey, 07059, United States

Location

Gallup Indian Medical Center

Gallup, New Mexico, 87301, United States

Location

Johns Hopkins Center for American Indian Health

Gallup, New Mexico, 87301, United States

Location

Johns Hopkins Center for American Indian Health

Shiprock, New Mexico, 87420, United States

Location

Northern Navajo Medical Center

Shiprock, New Mexico, 87420, United States

Location

Meridian Clinical Research LLC

Binghamton, New York, 13901, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Rochester Clinical Research, Inc.

Rochester, New York, 14609, United States

Location

University of Rochester Medical Center- Kari Steinmetz

Rochester, New York, 14642, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13215, United States

Location

Velocity Clinical Research, Vestal

Vestal, New York, 13850, United States

Location

Accellacare

Cary, North Carolina, 27518, United States

Location

Accellacare

Charlotte, North Carolina, 28211, United States

Location

Duke University - Main Hospital and Clinics

Durham, North Carolina, 27703, United States

Location

PharmQuest Life Sciences, LLC

Greensboro, North Carolina, 27408, United States

Location

Accellacare

Hickory, North Carolina, 28601, United States

Location

Accellacare

Raleigh, North Carolina, 27609, United States

Location

M3 Wake Research, Inc.

Raleigh, North Carolina, 27612, United States

Location

Accellacare - Salisbury

Salisbury, North Carolina, 28144, United States

Location

Accellacare (formerly PMG Research of Wilmington, LLC)

Wilmington, North Carolina, 28401, United States

Location

Accellacare

Wilmington, North Carolina, 28401, United States

Location

Accellacare

Winston-Salem, North Carolina, 27103, United States

Location

Lillestol Research

Fargo, North Dakota, 58104, United States

Location

Meridian Clinical Research, LLC

Cincinnati, Ohio, 45219, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Meridian Clinical Research

Cincinnati, Ohio, 45246, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

VA Northeast Ohio Healthcare System

Cleveland, Ohio, 44106, United States

Location

Velocity Clinical Research, Cleveland

Cleveland, Ohio, 44122, United States

Location

Centricity Research Columbus Ohio Multispecialty

Columbus, Ohio, 43213, United States

Location

Dayton Clinical Research

Dayton, Ohio, 45406, United States

Location

Dayton Clinical Research

Dayton, Ohio, 45409, United States

Location

PriMED Clinical Research

Dayton, Ohio, 45419, United States

Location

Senders Pediatrics

South Euclid, Ohio, 44121, United States

Location

Lynn Institute of Norman

Norman, Oklahoma, 73072, United States

Location

Kaiser Permanente Center for Health Research

Portland, Oregon, 97227, United States

Location

Lehigh Valley Health Network/Network Office of Research and Innovation

Allentown, Pennsylvania, 18102, United States

Location

Velocity Clinical Research, Providence

East Greenwich, Rhode Island, 02818, United States

Location

Main Street Physician's Care

Little River, South Carolina, 29566, United States

Location

Holston Medical Group

Bristol, Tennessee, 37620, United States

Location

Holston Medical Group

Kingsport, Tennessee, 37660, United States

Location

Alliance for Multispecialty Research - Weisgarber Medical Park

Knoxville, Tennessee, 37909, United States

Location

Clinical Neuroscience Solutions Inc.

Memphis, Tennessee, 38119, United States

Location

Clinical Research Associates Inc

Nashville, Tennessee, 37203, United States

Location

Trinity Clinical Research

Tullahoma, Tennessee, 37388, United States

Location

Benchmark Research

Austin, Texas, 78705, United States

Location

Innovo Research - Austin Regional Clinic

Austin, Texas, 78726, United States

Location

Tekton Research, Inc

Austin, Texas, 78745, United States

Location

North Texas Infectious Diseases Consultants, P.A

Dallas, Texas, 75246, United States

Location

Ventavia Research Group

Fort Worth, Texas, 76104, United States

Location

Benchmark Research

Fort Worth, Texas, 76135, United States

Location

HG Pediatrics

Houston, Texas, 77008, United States

Location

Renu Garg, MD Pediatrics

Houston, Texas, 77008, United States

Location

Van Tran Family Practice

Houston, Texas, 77008, United States

Location

Ventavia Research Group, LLC

Houston, Texas, 77008, United States

Location

DM Clinical Research - Bellaire

Houston, Texas, 77081, United States

Location

SCR of Texas, LLC

Keller, Texas, 76248, United States

Location

SMS Clinical Research

Mesquite, Texas, 75149, United States

Location

LinQ Research, LLC

Pearland, Texas, 77584, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

Clinical Trials of Texas, LLC

San Antonio, Texas, 78229, United States

Location

IMA Clinical Research San Antonio

San Antonio, Texas, 78229, United States

Location

DM Clinical Research - Kool Kids Pediatrics

Tomball, Texas, 77375, United States

Location

DM Clinical Research

Tomball, Texas, 77375, United States

Location

J. Lewis Research, Inc. / Foothill Family Clinic

Salt Lake City, Utah, 84109, United States

Location

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

Salt Lake City, Utah, 84121, United States

Location

Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID)

Annandale, Virginia, 22003, United States

Location

Virginia Research Center

Midlothian, Virginia, 23114, United States

Location

Benaroya Research Institute at Virginia Mason

Seattle, Washington, 98101, United States

Location

Research Building

Wenatchee, Washington, 98801, United States

Location

Wenatchee Valley Hospital

Wenatchee, Washington, 98801, United States

Location

Obras Sociais Irma Dulce

Salvador, Estado de Bahia, 40.415-006, Brazil

Location

CEPIC - Centro Paulista de Investigação Clínica

São Paulo, 04266-010, Brazil

Location

Studienzentrum Dr. Keller

Frankfurt, 60389, Germany

Location

IKF Pneumologie GmbH & Co. KG

Frankfurt, 60596, Germany

Location

Sheba Medical Center

Ramat Gan, Central District, 5262100, Israel

Location

Synergy Biomed Research Institute

East London, Eastern Cape, 5201, South Africa

Location

Worthwhile Clinical Trials

Benoni, Gauteng, 1501, South Africa

Location

Newtown Clinical Research

Johannesburg, Gauteng, 2113, South Africa

Location

Clinresco Centres

Kempton Park, Gauteng, 1619, South Africa

Location

Dr A Jacovides & Partners Inc.

Midrand, Gauteng, 1685, South Africa

Location

Botho Ke Bontle Health Services PTY LTD

Pretoria, Gauteng, 0184, South Africa

Location

Limpopo Clinical Research Initiative

Thabazimbi, Limpopo, 0380, South Africa

Location

TREAD Research

Cape Town, Parow, 7500, South Africa

Location

Tiervlei Trial Centre

Cape Town, Western Cape, 7530, South Africa

Location

Jongaie Research

Pretoria, 0183, South Africa

Location

Related Publications (4)

• Winokur P, Diya O, Fitz-Patrick D, Dever M, Gayed J, Lockhart S, Xu X, Zhang Y, Bangad V, Wadsworth LT, Cannon K, Cardona JF, Usdan L, Ginis J, Mensa FJ, Zou J, Xie X, Lu C, Buitrago S, Scully IL, Cooper D, Koury K, Jansen KU, Tureci Ӧ, Sahin U, Swanson KA, Gruber WC, Kitchin N. Safety and Immunogenicity of a Fourth Dose of Omicron-BA.1-Adapted BNT162b2 COVID-19 Vaccines in Adults 18-55 Years Old. Clin Infect Dis. 2026 Jan 21:ciag026. doi: 10.1093/cid/ciag026. Online ahead of print.

  PMID: 41560517 DERIVED

• Muik A, Lui BG, Quandt J, Diao H, Fu Y, Bacher M, Gordon J, Toker A, Grosser J, Ozhelvaci O, Grikscheit K, Hoehl S, Kohmer N, Lustig Y, Regev-Yochay G, Ciesek S, Beguir K, Poran A, Vogler I, Tureci O, Sahin U. Progressive loss of conserved spike protein neutralizing antibody sites in Omicron sublineages is balanced by preserved T cell immunity. Cell Rep. 2023 Aug 29;42(8):112888. doi: 10.1016/j.celrep.2023.112888. Epub 2023 Jul 31.

  PMID: 37527039 DERIVED

• Winokur P, Gayed J, Fitz-Patrick D, Thomas SJ, Diya O, Lockhart S, Xu X, Zhang Y, Bangad V, Schwartz HI, Denham D, Cardona JF, Usdan L, Ginis J, Mensa FJ, Zou J, Xie X, Shi PY, Lu C, Buitrago S, Scully IL, Cooper D, Koury K, Jansen KU, Tureci O, Sahin U, Swanson KA, Gruber WC, Kitchin N; C4591031 Clinical Trial Group. Bivalent Omicron BA.1-Adapted BNT162b2 Booster in Adults Older than 55 Years. N Engl J Med. 2023 Jan 19;388(3):214-227. doi: 10.1056/NEJMoa2213082.

  PMID: 36652353 DERIVED

• Moreira ED Jr, Kitchin N, Xu X, Dychter SS, Lockhart S, Gurtman A, Perez JL, Zerbini C, Dever ME, Jennings TW, Brandon DM, Cannon KD, Koren MJ, Denham DS, Berhe M, Fitz-Patrick D, Hammitt LL, Klein NP, Nell H, Keep G, Wang X, Koury K, Swanson KA, Cooper D, Lu C, Tureci O, Lagkadinou E, Tresnan DB, Dormitzer PR, Sahin U, Gruber WC, Jansen KU; C4591031 Clinical Trial Group. Safety and Efficacy of a Third Dose of BNT162b2 Covid-19 Vaccine. N Engl J Med. 2022 May 19;386(20):1910-1921. doi: 10.1056/NEJMoa2200674. Epub 2022 Mar 23.

  PMID: 35320659 DERIVED

Related Links

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

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

BNT162 Vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

mRNA Vaccines; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines; Antigens; Biological Factors

Results Point of Contact

• Title: BioNTech SE
• Organization: BioNTech clinical trials patient information

patients@biontech.de

+49 6131 90840

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: July 9, 2021
• Study Start: July 1, 2021
• Primary Completion: May 25, 2023
• Study Completion: May 25, 2023
• Last Updated: November 10, 2025
• Results First Posted: November 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (139); ZA (10); BR (2); IL (1); DE (2)