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Phase 3 N=16,349 Randomized Triple-blind Prevention

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

SARS-CoV-2 Infection · COVID-19

Enrolled (actual)
16,349
Serious AEs
1.0%
Results posted
Nov 2025
Primary outcome: Primary: 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 — 7.290; 155.303 Number of first Covid-19 cases/1000 PY

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
BNT162b2 (Biological); Placebo (Other); BNT162b2 OMI (Biological); Combination BNT162b2 and BNT162b2 OMI (Biological); Combination (Bivalent) BNT162b2 and BNT162b2 OMI (Biological)
Age
Pediatric, Adult, Older Adult · 12+ yrs
Sex
All
Sponsor
BioNTech SE
Primary completion
May 2023

Outcome Measures

OutcomeResultp-value
PRIMARY
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
7.290; 155.303
PRIMARY
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
8.037; 148.503
PRIMARY
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
57.377; 158.798
PRIMARY
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
57.118; 151.668
PRIMARY
SSA: Percentage of Participants Reporting Adverse Events
26.3; 7.1
PRIMARY
SSA: Percentage of Participants Reporting Serious Adverse Events (SAE)
1.4; 0.8; 1.0
PRIMARY
SSB: Percentage of Participants With Elevated Troponin I Level Pre-Dose; Vaccination 1
0.7; 0.5
PRIMARY
SSB: Percentage of Participants With Elevated Troponin I Level Within 5 Days After Vaccination 1
1.0; 0.6
PRIMARY
SSB: Percentage of Participants With Elevated Troponin I Level Pre-Vaccination 2 (1 Month After Vaccination 1)
1.1; 0.3
PRIMARY
SSB: Percentage of Participants With Elevated Troponin I Level Within 5 Days After Vaccination 2
1.5; 0.3
PRIMARY
SSB: Percentage of Participants With Elevated Troponin I Level 1 Month After Vaccination 2
0.7; 0.3
PRIMARY
SSB: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1
5.8; 0.5; 4.4; 0.4; 1.1; 0.1
PRIMARY
SSB: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2
0.7; 4.6; 0.3; 2.8; 0.4; 1.5
PRIMARY
SSB: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1
6.0; 1.9; 4.1; 1.4; 1.7; 0.3
PRIMARY
SSB: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2
0.4; 4.3; 0.3; 2.5; 0.1; 1.3
PRIMARY
SSB: Percentage of Participants Reporting Adverse Events (AEs) 1 Month After Vaccination 1
9.4; 10.4
PRIMARY
SSB: Percentage of Participants Reporting Adverse Events (AEs) 1 Month After Vaccination 2
5.6; 7.4
PRIMARY
SSB: Percentage of Participants Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 1
0.1; 0.3
PRIMARY
SSB: Percentage of Participants Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 2
0; 0.1
PRIMARY
SSC: Percentage of Participants With Local Reactions Within 7 Days After Booster Dose
1.3; 6.3; 1.3; 4.7; 0; 1.6
PRIMARY
SSC: Percentage of Participants With Systemic Events Within 7 Days After Booster Dose
4.0; 6.3; 2.7; 3.1; 0; 1.6
PRIMARY
SSC: Percentage of Participants Reporting Adverse Events From Booster Dose Through 1 Month After Booster Dose
4.0; 7.7
PRIMARY
SSC: Percentage of Participants Reporting Serious Adverse Events From Booster Dose Through 6 Months After Booster Dose
0; 1.5
PRIMARY
SSC: Geometric Mean Titers (GMT) of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Baseline
1337.2; 1648.4
PRIMARY
SSC: GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at 1 Month After the Booster Dose
11672.4; 15680.7
PRIMARY
SSC: Geometric Mean Fold-Rise (GMFR) of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Baseline to 1 Month After the Booster Dose
8.6; 9.5
PRIMARY
SSC: Percentage of Participants With Seroresponse to Reference-Strain at 1 Month After the Booster Dose
67.7; 66.7
PRIMARY
SSD: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 1
3.4; 5.7; 2.5; 7.1; 4.3; 5.4
PRIMARY
SSD: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 2
5.7; 5.1; 4.1; 4.3; 4.5; 3.6
PRIMARY
SSD: Percentage of Participants With Local Reactions Within 7 Days After Vaccination 3
4.5; 1.3; 3.2; 0; 0; 10.4
PRIMARY
SSD: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 1
5.8; 2.6; 5.0; 8.8; 7.2; 4.8
PRIMARY
SSD: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 2
1.3; 5.1; 6.0; 2.1; 0; 2.6
PRIMARY
SSD: Percentage of Participants With Systemic Events Within 7 Days After Vaccination 3
2.6; 0.6; 1.3; 0.6; 0; 22.7
PRIMARY
SSD: Percentage of Participants Reporting Adverse Events (AEs) From First Study Vaccination (Day 1) Through 1 Month After Last Study Vaccination: Cohort 1
3.2; 6.1; 2.0
PRIMARY
SSD: Percentage of Participants Reporting Adverse Events (AEs) From First Study Vaccination (Day 1) Through 1 Month After Vaccination 1: Cohort 2
4.1; 3.7
PRIMARY
SSD: Percentage of Participants Reporting Adverse Events (AEs) From Second Study Vaccination Through 1 Month After Second Study Vaccination: Cohort 2
2.3; 3.8
PRIMARY
SSD: Percentage of Participants Reporting Adverse Events (AEs) From First Study Vaccination (Day 1) Through 1 Month After Second Study Vaccination: Cohort 3
6.7
PRIMARY
SSD: Percentage of Participants Reporting Adverse Events (AEs) From Third Study Vaccination Through 1 Month After Third Study Vaccination: Cohort 3
0.6
PRIMARY
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
0.9; 1.5; 1.0; 3.8
PRIMARY
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
1.6; 0.6
PRIMARY
SSD: Percentage of Participants Reporting Serious Adverse Events (SAEs) From First Study Vaccination Through 6 Months After Vaccination 2: Cohort 2
0.5; 1.3
PRIMARY
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
1929.2; 1099.6
PRIMARY
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
62.3; 39.3
PRIMARY
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
5094.1; 1775.6
PRIMARY
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
4684.3; 1775.6
PRIMARY
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
88.0; 59.0
PRIMARY
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
80.0; 59.0
PRIMARY
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
2892.2; 290.6
PRIMARY
SSD: Percentage of Participants With Seroresponse to the SARS-CoV-2 Omicron BA.1 Strain at 1 Month After Second Study Vaccination: Cohort 3
86.2; 80.8
PRIMARY
SSE: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination
6.7; 0; 6.7; 8.1; 6.3; 10.9
PRIMARY
SSE: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination
13.3; 0; 10.0; 10.0; 10.8; 19.4
PRIMARY
SSE: Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination
13.3; 6.7; 13.3; 7.7; 6.3; 9.3
PRIMARY
SSE: Percentage of Participants Reporting Serious Adverse Events (SAEs) Within 6 Month After Study Vaccination
0; 0; 0; 0.6; 1.3; 0.9
PRIMARY
SSE: Percentage of Participants With Elevated Troponin I Levels Before the Study Vaccination- 18 to 55 Years of Age
0; 0; 0
PRIMARY
SSE: Percentage of Participants With Elevated Troponin I Levels 3 Days After Study Vaccination- 18 to 55 Years of Age
0; 0; 0
PRIMARY
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
455.8; 1014.5; 1435.2; 711.0; 900.1
PRIMARY
SSE: Percentage of Participants With Seroresponse to the SARS-CoV-2 Omicron BA.1 Strain at 1 Month After Study Vaccination
57.0; 76.7; 86.1; 71.6; 67.9
PRIMARY
SSF: Geometric Mean Titer (GMTs) of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers Before Vaccination
41.7; 33.2; 32.0; 36.8; 78.8; 21.5
PRIMARY
SSF: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination
19.0; 21.1; 23.8; 20.0; 10.0; 28.6
PRIMARY
SSF: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination
9.5; 10.5; 9.5; 10.0; 5.0; 4.8
PRIMARY
SSF: Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination
0; 10.5; 9.5; 5.0; 10.0; 0
PRIMARY
SSF: Percentage of Participants Reporting Serious Adverse Events (SAEs) Within 6 Months After Study Vaccination
0; 5.3; 4.8; 0; 5.0; 0
PRIMARY
SSF: GMTs of SARS-CoV-2 Reference-Strain-Neutralizing Titers Before Vaccination
541.1; 382.4; 437.5; 315.2; 803.4; 256.0
PRIMARY
SSF: GMTs of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers Before Vaccination
27.1; 18.0; 20.2; 23.4; 42.2; 15.0
PRIMARY
SSF: Geometric Mean Ratio (GMR) Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Day 7
146.1; 101.6; 217.1; 315.2; 337.8; 222.9
PRIMARY
SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Day 7
1917.2; 1241.4; 1472.3; 1499.2; 2702.4; 1845.8
PRIMARY
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers at Day 7
75.5; 56.6; 73.0; 76.1; 123.6; 70.7
PRIMARY
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Month 1
420.0; 188.1; 699.4; 675.6; 1024.0; 477.7
PRIMARY
SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Month 1
4674.1; 2048.4; 3327.0; 3565.8; 5404.7; 2521.4
PRIMARY
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 1
157.6; 85.7; 151.0; 230.7; 284.0; 147.0
PRIMARY
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Month 3
247.3; 118.5; 461.4; 711.0; 512.0; 285.6
PRIMARY
SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Month 3
2896.3; 1290.2; 2610.3; 2949.6; 2610.3; 1474.8
PRIMARY
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 3
222.9; 132.8; 322.5; 458.9; 296.2; 141.3
PRIMARY
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers at Month 6
239.6; 229.5; 1058.4; 1722.2; 588.1; 284.0
PRIMARY
SSF: GMR Based on GMT of SARS-CoV-2 Reference-Strain-Neutralizing Titers at Month 6
1424.5; 1371.0; 2756.4; 3956.5; 2702.4; 1097.5
PRIMARY
SSF: GMR Based on GMT of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 6
203.2; 265.5; 645.1; 1305.2; 430.5; 187.4
PRIMARY
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
3.5; 2.9; 6.8; 8.6; 4.3; 9.8
PRIMARY
SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 7 Days After Vaccination
3.5; 3.1; 3.4; 4.8; 3.4; 6.3
PRIMARY
SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 7 Days After Vaccination
2.8; 2.8; 3.6; 3.2; 2.9; 4.7
PRIMARY
SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination
10.1; 5.4; 20.4; 18.4; 13.0; 21.1
PRIMARY
SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination
8.6; 5.0; 7.2; 11.3; 6.7; 8.6
PRIMARY
SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination
5.9; 4.7; 7.5; 9.8; 6.7; 9.5
PRIMARY
SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination
5.9; 3.3; 13.5; 17.9; 6.5; 12.0
PRIMARY
SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination
5.0; 3.2; 5.6; 8.6; 3.2; 4.5
PRIMARY
SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination
8.6; 7.4; 16.0; 18.5; 7.2; 9.4
PRIMARY
SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain-Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination
5.8; 6.9; 33.1; 46.9; 7.5; 12.6
PRIMARY
SSF: GMFR of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination
2.6; 3.6; 6.3; 12.6; 3.4; 3.9
PRIMARY
SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain-Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination
7.5; 16.6; 32.0; 55.7; 10.2; 13.0
PRIMARY
SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Day 7
52.4; 44.4; 71.4; 85.0; 55.0; 90.0
PRIMARY
SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Day 7
52.4; 55.6; 61.9; 80.0; 55.0; 80.0
PRIMARY
SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Day 7
33.3; 43.8; 42.9; 40.0; 40.0; 61.9
PRIMARY
SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 1
85.7; 61.1; 90.0; 85.0; 90.0; 85.0
PRIMARY
SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 1
81.0; 61.1; 85.0; 85.0; 70.0; 75.0
PRIMARY
SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 1
75.0; 61.1; 66.7; 95.0; 80.0; 85.0
PRIMARY
SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 3
65.0; 50.0; 75.0; 84.2; 70.0; 89.5
PRIMARY
SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 3
65.0; 55.6; 65.0; 78.9; 55.0; 63.2
PRIMARY
SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 3
75.0; 61.1; 85.7; 84.2; 63.2; 85.7
PRIMARY
SSF: Percentage of Participants With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 6
42.9; 47.4; 85.7; 90.0; 65.0; 85.0
PRIMARY
SSF: Percentage of Participants With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 6
42.9; 42.1; 61.9; 85.0; 55.0; 50.0
PRIMARY
SSF: Percentage of Participants With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 6
52.4; 50.0; 85.7; 90.0; 70.0; 75.0
SECONDARY
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
0; 2.103
SECONDARY
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
0; 1.978
SECONDARY
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
0; 0
SECONDARY
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
0; 0
SECONDARY
SSC: GMTs of SARS-CoV-2 Reference-Strain Neutralizing Titers at Baseline and 7 Days After the Booster Dose
1846.7; 2230.4; 15193.4; 22689.7
SECONDARY
SSC: GMTs of SARS-CoV-2 Omicron BA.1- Neutralizing Titers at Baseline and 7 Days After the Booster Dose
68.2; 131.1; 1356.4; 2655.7
SECONDARY
SSC: GMFRs of SARS-CoV-2 Reference-Strain-Neutralizing Titers From Baseline to 7 Days After the Booster Dose
8.2; 10.2
SECONDARY
SSC: GMFRs of SARS-CoV-2 Omicron BA.1-Neutralizing Titers From Baseline to 7 Days After the Booster Dose
19.7; 20.2
SECONDARY
SSC: Percentages of Participants With Seroresponse to Reference Strain at 7 Days After the Booster Dose
71.2; 68.1
SECONDARY
SSC: Percentages of Participants With Seroresponse to Omicron BA.1 at 7 Days After the Booster Dose
77.6; 74.5
SECONDARY
SSE: GMR Based on Geometric Mean Titers of SARS-CoV-2 Reference Strain Neutralizing Titers at 1 Month After the Study Vaccination- >55 Years of Age
5998.1; 5933.2; 7816.9

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

Eligibility Criteria

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 microbi
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Data sourced from ClinicalTrials.gov (NCT04955626). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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