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Clinical Trial Results:
A Master Phase 1/2/3 Protocol to Investigate the Safety, Tolerability, and Immunogenicity of Variant- Adapted BNT162b2 RNA-Based Vaccine Candidate (s) in Healthy Children

Summary
EudraCT number	2024-000001-33
Trial protocol	Outside EU/EEA
Global end of trial date

Results information
Results version number	v3(current)
This version publication date	11 May 2025
First version publication date	06 Mar 2024
Other versions	v1 , v2
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

Top of page

Sponsor protocol code

C4591048

ISRCTN number

US NCT number

NCT05543616

WHO universal trial number (UTN)

Sponsor organisation name

BioNTech SE

Sponsor organisation address

An der Goldgrube 12, Mainz, Germany, 55131

Public contact

BioNTech SE, BioNTech clinical trials patient information, +49 6131 90840, patients@biontech.de

Scientific contact

BioNTech SE, BioNTech clinical trials patient information, +49 6131 90840, patients@biontech.de

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-002861-PIP02-20

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Interim

Date of interim/final analysis

31 Oct 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Main objective of the trial

Substudy (SS) B: Assess safety, tolerability of bivalent BNT162b2 as 3rd/4th doses in participants >=6 months to <5 years. Compare anti-Omicron BA.4/BA.5 immune response in those receiving 3 prior 3 mcg doses of BNT162b2 vs. 4th dose in Group 2, and Phase 2/3 Study C4591007 participants with 3 doses of 3 mcg BNT162b2. SSC: Assess safety, tolerability of bivalent BNT162b2 as 4th dose in participants 6M-<5Y. Evaluate immune responses to 4th dose in this group. SSD: Assess safety, tolerability of bivalent BNT162b2 as 3rd/4th doses in 5-12Y. Compare anti-Omicron BA.4/BA.5 immune response in 5-12Y receiving 3 doses of 10 mcg BNT162b2 vs. 4th dose in Group 2, and Study C4591007 participants with 3 doses of 10 mcg. SSE: Evaluate safety, tolerability of prophylactic BNT162b2 (Omicron XBB.1.5) as a single dose in COVID-19 vaccine-naive participants >=5-<12 years, and immune response compared to vaccine-experienced participants >=12 years of age of BNT162b2 (Omi XBB.1.5) in Study C4591054 SSA.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials participants were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Sep 2022

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 1843

Country: Number of subjects enrolled

Brazil: 29

Country: Number of subjects enrolled

Puerto Rico: 2

Country: Number of subjects enrolled

South Africa: 65

Worldwide total number of subjects

1939

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

145

Children (2-11 years)

1794

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

Substudy (SS)B:1398 participants enrolled, 1397 vaccinated. SSC:100 randomised, 98 vaccinated.SSD:136 enrolled,134 vaccinated. SSE:310 enrolled and vaccinated. Data was reported at study completion date for SSB, SSC, SSD & SSE. PCD for SSA have not been reached; data collection is still ongoing, hence no data reported for SSA.

Period 1 title

Baseline Period

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

SSB: Group 1a: 2 prior doses of BNT162b2

Arm description

Participants aged >=6 months to <2 years who had received two prior doses of BNT162b2 3 microgram (mcg) with the last dose received 60 to 150 days before enrollment in the study were included. Participants received two doses (third and fourth dose) of BNT162b2 3 mcg via intramuscular route in this study. Third dose was administered on Day 1 of this study and fourth dose was administered approximately 2 months after third dose.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 micrograms Bivalent BNT162b2 administered intramuscularly.

SSB: Group 1b: 2 prior doses of BNT162b2

Arm description

Participants aged >=2 to <5 years who had received two prior doses of BNT162b2 3 mcg with the last dose received 60 to 150 days before enrollment in the study were included. Participants received two doses (third and fourth dose) of BNT162b2 3 mcg via intramuscular route in this study. Third dose was administered on Day 1 of this study and fourth dose was administered approximately 2 months after third dose.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 micrograms Bivalent BNT162b2 administered intramuscularly.

SSB: Group 2a: 3 prior doses of BNT162b2

Arm description

Participants aged >=6 months to <2 years who had received three prior doses of BNT162b2 10 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single dose (fourth) of BNT162b2 3 mcg via intramuscular route on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 micrograms Bivalent BNT162b2 administered intramuscularly.

SSB: Group 2b: 3 prior doses of BNT162b2

Arm description

Participants aged >=2 to <5 years who had received three prior doses of BNT162b2 10 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single dose (fourth) of BNT162b2 3 mcg via intramuscular route on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 micrograms Bivalent BNT162b2 administered intramuscularly.

SSB: Group 3a: 3 prior doses of BNT162b2

Arm description

Participants from C4591007 (NCT04816643) phase 1 trial, aged >=6 months to <2 years who had received three prior doses of BNT162b2 3 mcg with the last dose received at least 60 days before enrollment in the study were included. Participants received a single dose (fourth) of BNT162b2 3 mcg via intramuscular route on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 micrograms Bivalent BNT162b2 administered intramuscularly.

SSB: Group 3b: 3 prior doses of BNT162b2

Arm description

Participants from C4591007 (NCT04816643) phase 1 trial, aged >=2 to <5 years who had received three prior doses of BNT162b2 3 mcg with the last dose received at least 60 days before enrollment in the study were included. Participants received a single dose (fourth) of BNT162b2 3 mcg via intramuscular route on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 micrograms Bivalent BNT162b2 administered intramuscularly.

SSC: Group 1a: 3 prior doses of BNT162b2

Arm description

Participants aged >=6 months to <2 years who had received three prior doses of BNT162b2 3 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single (fourth) dose of BNT162b2 6 mcg via intramuscular route on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

6 micrograms Bivalent BNT162b2 administered intramuscularly.

SSC: Group 1b: 3 prior doses of BNT162b2

Arm description

Participants aged >=6 months to <2 years who had received three prior doses of BNT162b2 3 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single (fourth) dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

10 micrograms Bivalent BNT162b2 administered intramuscularly.

SSC: Group 2a: 3 prior doses of BNT162b2

Arm description

Participants aged >=2 to <5 years who had received three prior doses of BNT162b2 3 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single (fourth) dose of BNT162b2 6 mcg via intramuscular route on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

6 micrograms Bivalent BNT162b2 administered intramuscularly.

SSC: Group 2b: 3 prior doses of BNT162b2

Arm description

Participants aged >=2 to <5 years who had received three prior doses of BNT162b2 3 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single (fourth) dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

10 micrograms Bivalent BNT162b2 administered intramuscularly.

SSD: Group 1: 2 prior doses of BNT162b2

Arm description

Participants aged 5 to 11 years who had received two prior doses of BNT162b2 10 microgram (mcg) 90 to 240 days before enrollment in the study were included. Participants received a single dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

10 micrograms (original BNT162b2 5 mcg and BNT162b2 Omicron [B.1.1.529 sublineage BA.4/BA.5] 5 mcg) administered intramuscularly.

SSD: Group 2: 3 prior doses of BNT162b2

Arm description

Participants aged 5 to11 years who had received three prior doses of BNT162b2 10 mcg 90 to 240 days before enrollment in the study were included. Participants received a single dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

10 micrograms (original BNT162b2 5 mcg and BNT162b2 Omicron [B.1.1.529 sublineage BA.4/BA.5] 5 mcg) administered intramuscularly.

SSD Group 3:Participants from study C4591007 Phase 1

Arm description

Participants from C4591007 (NCT04816643) phase 1 trial, aged 5 to 11 years who had received three prior doses of BNT162b2 10 mcg at least 90 days before enrollment in the study were included. Participants received a single dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

10 micrograms (original BNT162b2 5 mcg and BNT162b2 Omicron [B.1.1.529 sublineage BA.4/BA.5] 5 mcg) administered intramuscularly.

SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg

Arm description

Participants aged 5 to 11 years who received a single dose of BNT162b2 (Omi XBB.1.5) 10 mcg via intramuscular route on Day 1 of this sub-study.

Arm type

Experimental

Investigational medicinal product name

Monovalent BNT162b2 (Omi XBB.1.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

10 micrograms BNT162b2 (Omicron XBB.1.5) administered intramuscularly.

Number of subjects in period 1	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2	SSB: Group 3a: 3 prior doses of BNT162b2	SSB: Group 3b: 3 prior doses of BNT162b2	SSC: Group 1a: 3 prior doses of BNT162b2	SSC: Group 1b: 3 prior doses of BNT162b2	SSC: Group 2a: 3 prior doses of BNT162b2	SSC: Group 2b: 3 prior doses of BNT162b2	SSD: Group 1: 2 prior doses of BNT162b2	SSD: Group 2: 3 prior doses of BNT162b2	SSD Group 3:Participants from study C4591007 Phase 1	SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg
Started	17	13	92	218	68	989	17	19	32	30	2	113	19	310
Completed	17	13	92	218	68	989	17	19	32	30	2	113	19	310

Period 2 title

Phase 1

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Single blind

Roles blinded

Subject

Blinding implementation details

Single blinded sponsor open label

Are arms mutually exclusive

SSC: Group 1a: 3 prior doses of BNT162b2

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

6 micrograms BNT162b2 administered intramuscularly.

SSC: Group 1b: 3 prior doses of BNT162b2

Arm description

Participants aged >=6 months to <2 years who had received three prior doses of BNT162b2 3 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single (fourth) dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

10 micrograms BNT162b2 administered intramuscularly.

SSC: Group 2a: 3 prior doses of BNT162b2

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

6 micrograms BNT162b2 administered intramuscularly.

SSC: Group 2b: 3 prior doses of BNT162b2

Arm description

Participants aged >=2 to <5 years who had received three prior doses of BNT162b2 3 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single (fourth) dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

10 micrograms BNT162b2 administered intramuscularly.

Number of subjects in period 2	SSC: Group 1a: 3 prior doses of BNT162b2	SSC: Group 1b: 3 prior doses of BNT162b2	SSC: Group 2a: 3 prior doses of BNT162b2	SSC: Group 2b: 3 prior doses of BNT162b2
Started	17	19	32	30
Completed	17	18	32	30
Not completed	0	1	0	0
Lost to follow-up	-	1	-	-

Period 3 title

Phase 3

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Blinding implementation details

Open Label Period

Are arms mutually exclusive

Yes

SSB: Group 1a: 2 prior doses of BNT162b2

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 micrograms Bivalent BNT162b2 administered intramuscularly.

SSB: Group 1b: 2 prior doses of BNT162b2

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 micrograms Bivalent BNT162b2 administered intramuscularly.

SSB: Group 2a: 3 prior doses of BNT162b2

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 micrograms Bivalent BNT162b2 administered intramuscularly.

SSB: Group 2b: 3 prior doses of BNT162b2

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 micrograms Bivalent BNT162b2 administered intramuscularly.

SSB: Group 3a: 3 prior doses of BNT162b2

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 micrograms Bivalent BNT162b2 administered intramuscularly.

SSB: Group 3b: 3 prior doses of BNT162b2

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

3 micrograms Bivalent BNT162b2 administered intramuscularly.

SSD: Group 1: 2 prior doses of BNT162b2

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

10 micrograms (original BNT162b2 5 mcg and BNT162b2 Omicron [B.1.1.529 sublineage BA.4/BA.5] 5 mcg) administered intramuscularly.

SSD: Group 2: 3 prior doses of BNT162b2

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

10 micrograms (original BNT162b2 5 mcg and BNT162b2 Omicron [B.1.1.529 sublineage BA.4/BA.5] 5 mcg) administered intramuscularly.

SSD Group 3:Participants from study C4591007 Phase 1

Arm description

Arm type

Experimental

Investigational medicinal product name

Bivalent BNT162b2 (original/Omicron BA.4/BA.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

10 micrograms (original BNT162b2 5 mcg and BNT162b2 Omicron [B.1.1.529 sublineage BA.4/BA.5] 5 mcg) administered intramuscularly.

SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg

Arm description

Participants aged 5 to 11 years who received a single dose of BNT162b2 (Omi XBB.1.5) 10 mcg via intramuscular route on Day 1 of this sub-study.

Arm type

Experimental

Investigational medicinal product name

Monovalent BNT162b2 (Omi XBB.1.5)

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

10 micrograms BNT162b2 (Omicron XBB.1.5) administered intramuscularly.

Number of subjects in period 3	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2	SSB: Group 3a: 3 prior doses of BNT162b2	SSB: Group 3b: 3 prior doses of BNT162b2	SSD: Group 1: 2 prior doses of BNT162b2	SSD: Group 2: 3 prior doses of BNT162b2	SSD Group 3:Participants from study C4591007 Phase 1	SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg
Started	17	13	92	218	68	989	2	113	19	310
Completed	17	11	89	210	67	969	2	111	19	287
Not completed	0	2	3	8	1	20	0	2	0	23
Physician decision	-	-	-	-	-	1	-	-	-	-
Consent withdrawn by subject	-	-	-	-	-	-	-	1	-	-
Withdrawal by parents/guardian	-	2	3	7	-	4	-	1	-	1
Lost to follow-up	-	-	-	-	1	12	-	-	-	17
Protocol deviation	-	-	-	1	-	3	-	-	-	5

Baseline characteristics

Top of page

Reporting group title

SSB: Group 1a: 2 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 1b: 2 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 2a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 2b: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 3a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 3b: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSC: Group 1a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSC: Group 1b: 3 prior doses of BNT162b2

Reporting group description

Participants aged >=6 months to <2 years who had received three prior doses of BNT162b2 3 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single (fourth) dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Reporting group title

SSC: Group 2a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSC: Group 2b: 3 prior doses of BNT162b2

Reporting group description

Participants aged >=2 to <5 years who had received three prior doses of BNT162b2 3 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single (fourth) dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Reporting group title

SSD: Group 1: 2 prior doses of BNT162b2

Reporting group description

Reporting group title

SSD: Group 2: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSD Group 3:Participants from study C4591007 Phase 1

Reporting group description

Reporting group title

SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg

Reporting group description

Participants aged 5 to 11 years who received a single dose of BNT162b2 (Omi XBB.1.5) 10 mcg via intramuscular route on Day 1 of this sub-study.

Reporting group values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2	SSB: Group 3a: 3 prior doses of BNT162b2	SSB: Group 3b: 3 prior doses of BNT162b2	SSC: Group 1a: 3 prior doses of BNT162b2	SSC: Group 1b: 3 prior doses of BNT162b2	SSC: Group 2a: 3 prior doses of BNT162b2	SSC: Group 2b: 3 prior doses of BNT162b2	SSD: Group 1: 2 prior doses of BNT162b2	SSD: Group 2: 3 prior doses of BNT162b2	SSD Group 3:Participants from study C4591007 Phase 1	SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg	Total
Number of subjects	17	13	92	218	68	989	17	19	32	30	2	113	19	310	1939
Age categorical
Units: Subjects
In Utero	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestional age < 37 wks)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days - 23 months)	17	0	92	0	68	0	17	0	32	0	0	0	0	0	226
Children (2 - 11 years)	0	13	0	218	0	989	0	19	0	30	2	113	19	310	1713
12 - 17 years	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Adults (18 - 64 years)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
From 65 - 84 years	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gender categorical
Units: Subjects
Male	12	6	51	105	38	477	9	8	16	17	2	57	8	146	952
Female	5	7	41	113	30	512	8	11	16	13	0	56	11	164	987
Race
Units: Subjects
White	14	7	64	153	58	775	13	18	25	23	2	66	12	128	1358
Black or African American	0	0	2	7	5	51	0	1	2	1	0	9	2	164	244
Asian	1	4	11	18	3	57	2	0	2	3	0	13	2	6	122
Multiracial	1	2	15	39	2	100	2	0	3	3	0	22	3	10	202
Not reported	1	0	0	1	0	2	0	0	0	0	0	3	0	1	8
Native Hawaiian or other Pacific Islander	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1
American Indian or Alaska Native	0	0	0	0		3	0	0	0	0	0	0	0	1	4
Ethnicity
Units: Subjects
Hispanic/Latino	3	2	18	34	12	136	2	2	1	0	0	23	0	162	395
Non-Hispanic/non-Latino	13	11	74	184	56	852	15	17	31	30	2	90	19	148	1542
Not reported	1	0	0	0	0	1	0	0	0	0	0	0	0	0	2

Subject analysis set title

SSB Historical cohort:C4591007 BNT162b2 >=6 months to<2 years

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged >=6 months to <2 years from study C4591007 (NCT04816643) who received 3 doses of original BNT162b2 3 mcg were included.

Subject analysis set title

SSB Historical cohort: C4591007 BNT162b2 3 mcg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged >=2 to <5 years from study C4591007 (NCT04816643) who received 3 doses of original BNT162b2 3 mcg were included.

Subject analysis set title

SSD Historical cohort: C4591007 BNT162b2 10 mcg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged >=5 to <12 years from study C4591007 (NCT04816643) who received 3 doses of original BNT162b2 10 mcg were included.

Subject analysis set title

SSE Historical Cohort: C4591054 BNT162b2 (Omi XBB.1.5) 30mcg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged >=12 years who had received single dose of BNT162b2 (Omi XBB.1.5) 30 mcg in study C4591054 [NCT05997290]. Only the relevant data was used for analysis as planned, these participants were not enrolled in this study.

Subject analysis sets values	SSB Historical cohort:C4591007 BNT162b2 >=6 months to<2 years	SSB Historical cohort: C4591007 BNT162b2 3 mcg	SSD Historical cohort: C4591007 BNT162b2 10 mcg	SSE Historical Cohort: C4591054 BNT162b2 (Omi XBB.1.5) 30mcg
Number of subjects	72	167	113	300
Age categorical
Units: Subjects
In Utero				0
Preterm newborn infants (gestional age < 37 wks)				0
Newborns (0-27 days)				0
Infants and toddlers (28 days - 23 months)				0
Children (2 - 11 years)				0
12 - 17 years				0
Adults (18 - 64 years)				0
From 65 - 84 years				0
85 years and over				0
Age continuous
Units:
	( )	( )	( )	( )
Gender categorical
Units: Subjects
Male				0
Female				0
Race
Units: Subjects
White				0
Black or African American				0
Asian				0
Multiracial				0
Not reported				0
Native Hawaiian or other Pacific Islander				0
American Indian or Alaska Native				0
Ethnicity
Units: Subjects
Hispanic/Latino				0
Non-Hispanic/non-Latino				0
Not reported				0

End points

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Reporting group title

SSB: Group 1a: 2 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 1b: 2 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 2a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 2b: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 3a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 3b: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSC: Group 1a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSC: Group 1b: 3 prior doses of BNT162b2

Reporting group description

Participants aged >=6 months to <2 years who had received three prior doses of BNT162b2 3 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single (fourth) dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Reporting group title

SSC: Group 2a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSC: Group 2b: 3 prior doses of BNT162b2

Reporting group description

Participants aged >=2 to <5 years who had received three prior doses of BNT162b2 3 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single (fourth) dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Reporting group title

SSD: Group 1: 2 prior doses of BNT162b2

Reporting group description

Reporting group title

SSD: Group 2: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSD Group 3:Participants from study C4591007 Phase 1

Reporting group description

Reporting group title

SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg

Reporting group description

Participants aged 5 to 11 years who received a single dose of BNT162b2 (Omi XBB.1.5) 10 mcg via intramuscular route on Day 1 of this sub-study.

Reporting group title

SSC: Group 1a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSC: Group 1b: 3 prior doses of BNT162b2

Reporting group description

Participants aged >=6 months to <2 years who had received three prior doses of BNT162b2 3 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single (fourth) dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Reporting group title

SSC: Group 2a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSC: Group 2b: 3 prior doses of BNT162b2

Reporting group description

Participants aged >=2 to <5 years who had received three prior doses of BNT162b2 3 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single (fourth) dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Reporting group title

SSB: Group 1a: 2 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 1b: 2 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 2a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 2b: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 3a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 3b: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSD: Group 1: 2 prior doses of BNT162b2

Reporting group description

Reporting group title

SSD: Group 2: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSD Group 3:Participants from study C4591007 Phase 1

Reporting group description

Reporting group title

SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg

Reporting group description

Participants aged 5 to 11 years who received a single dose of BNT162b2 (Omi XBB.1.5) 10 mcg via intramuscular route on Day 1 of this sub-study.

Subject analysis set title

SSB Historical cohort:C4591007 BNT162b2 >=6 months to<2 years

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged >=6 months to <2 years from study C4591007 (NCT04816643) who received 3 doses of original BNT162b2 3 mcg were included.

Subject analysis set title

SSB Historical cohort: C4591007 BNT162b2 3 mcg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged >=2 to <5 years from study C4591007 (NCT04816643) who received 3 doses of original BNT162b2 3 mcg were included.

Subject analysis set title

SSD Historical cohort: C4591007 BNT162b2 10 mcg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants aged >=5 to <12 years from study C4591007 (NCT04816643) who received 3 doses of original BNT162b2 10 mcg were included.

Subject analysis set title

SSE Historical Cohort: C4591054 BNT162b2 (Omi XBB.1.5) 30mcg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Primary: SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 1 in Participants Aged >=6 months to <2 Years

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End point title

SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 1 in Participants Aged >=6 months to <2 Years ^[1] ^[2]

End point description

Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after study vaccination 1.Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and were graded as mild(>=0.5 to 2.0 cm), moderate (>2.0 to 7.0 cm), severe(>7.0 cm) & Grade (G) 4(necrosis [redness and swelling] or exfoliative dermatitis [redness]).Tenderness at injection site was graded as mild(hurts if gently touched),moderate(hurts if gently touched with crying),severe(causes limitation of limb movement) & G4 ER visit or hospitalisation. G4 were classified by investigator or medically qualified person. Percentage of participants with local reactions within 7 days after study vaccination 1 and associated 2-sided 95% CI based on Clopper and Pearson method. Safety population=all participants receiving at least 1dose of study intervention. Here, n=participants evaluable for the specified rows.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination 1 (i.e. third dose for Group 1a and fourth dose for Groups 2a and 3a) Description

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 3a: 3 prior doses of BNT162b2
Number of subjects analysed	17	92	68
Units: Percentage of participants
number (confidence interval 95%)
Redness: Any (n=17, 92, 68)	5.9 (0.1 to 28.7)	7.6 (3.1 to 15.1)	5.9 (1.6 to 14.4)
Redness: Mild (n=17, 92, 68)	5.9 (0.1 to 28.7)	7.6 (3.1 to 15.1)	4.4 (0.9 to 12.4)
Redness: Moderate (n=17, 92, 68)	0 (0.0 to 19.5)	0 (0.0 to 3.9)	1.5 (0.0 to 7.9)
Redness: Severe (n=17, 92, 68)	0 (0.0 to 19.5)	0 (0.0 to 3.9)	0 (0.0 to 5.3)
Redness: Grade 4 (n=17, 92, 68)	0 (0.0 to 19.5)	0 (0.0 to 3.9)	0 (0.0 to 5.3)
Swelling: Any (n=17, 92, 68)	0 (0.0 to 19.5)	5.4 (1.8 to 12.2)	1.5 (0.0 to 7.9)
Swelling: Mild (n=17, 92, 68)	0 (0.0 to 19.5)	5.4 (1.8 to 12.2)	1.5 (0.0 to 7.9)
Swelling: Moderate (n=17, 92, 68)	0 (0.0 to 19.5)	0 (0.0 to 3.9)	0 (0.0 to 5.3)
Swelling: Severe (n=17, 92, 68)	0 (0.0 to 19.5)	0 (0.0 to 3.9)	0 (0.0 to 5.3)
Swelling: Grade 4 (n=17, 92, 68)	0 (0.0 to 19.5)	0 (0.0 to 3.9)	0 (0.0 to 5.3)
Tenderness at injection site:Any (n=17,90,64)	23.5 (6.8 to 49.9)	12.2 (6.3 to 20.8)	12.5 (5.6 to 23.2)
Tenderness at injection site:Mild (n=17,90,64)	17.6 (3.8 to 43.4)	12.2 (6.3 to 20.8)	12.5 (5.6 to 23.2)
Tenderness at injection site:Moderate(n=17,90,64)	5.9 (0.1 to 28.7)	0 (0.0 to 4.0)	0 (0.0 to 5.6)
Tenderness at injection site:Severe (n=17,90, 64)	0 (0.0 to 19.5)	0 (0.0 to 4.0)	0 (0.0 to 5.6)
Tenderness at injection site:Grade 4 (n=17,90,64)	0 (0.0 to 19.5)	0 (0.0 to 4.0)	0 (0.0 to 5.6)

No statistical analyses for this end point

Primary: SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 2 in Participants Aged >=6 months to <2 Years: Group 1a Only

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End point title

SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 2 in Participants Aged >=6 months to <2 Years: Group 1a Only ^[3] ^[4]

End point description

Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after study vaccination 2. Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and were graded as mild (>=0.5 to 2.0 cm), moderate (>2.0 to 7.0 cm), severe(>7.0 cm)& G4 (necrosis [redness and swelling] or exfoliative dermatitis [redness]). Tenderness at injection site was graded as mild (hurts if gently touched), moderate (hurts if gently touched with crying),severe(causes limitation of limb movement) & G4 ER visit or hospitalisation.G4 were classified by investigator or medically qualified person. Percentage of participants with local reactions within 7 days after study vaccination 2 and associated 2-sided 95% CI based on Clopper and Pearson method. Safety population=all participants who received at least 1 dose of study intervention. This endpoint is reported for Group 1a only as only participants from Group 1a received two vaccinations in the study.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination 2 (i.e. fourth dose)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2
Number of subjects analysed	17
Units: Percentage of participants
number (confidence interval 95%)
Redness: Any	11.8 (1.5 to 36.4)
Redness: Mild	11.8 (1.5 to 36.4)
Redness: Moderate	0 (0.0 to 19.5)
Redness: Severe	0 (0.0 to 19.5)
Redness: Grade 4	0 (0.0 to 19.5)
Swelling: Any	5.9 (0.1 to 28.7)
Swelling: Mild	5.9 (0.1 to 28.7)
Swelling: Moderate	0 (0.0 to 19.5)
Swelling: Severe	0 (0.0 to 19.5)
Swelling: Grade 4	0 (0.0 to 19.5)
Tenderness at the injection site: Any	17.6 (3.8 to 43.4)
Tenderness at the injection site: Mild	11.8 (1.5 to 36.4)
Tenderness at the injection site: Moderate	0 (0.0 to 19.5)
Tenderness at the injection site: Severe	5.9 (0.1 to 28.7)
Tenderness at the injection site: Grade 4	0 (0.0 to 19.5)

No statistical analyses for this end point

Primary: SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 1 in Participants Aged >=6 months to <2 Years

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End point title

SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 1 in Participants Aged >=6 months to <2 Years ^[5] ^[6]

End point description

Systemic events recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after study vaccination 1. Fever: oral temperature >=38.0 deg C categorised as >=38.0 to 38.4 deg C,>38.4 to 38.9 deg C,>38.9 to 40.0 deg C and >40.0 deg C. Decreased appetite: mild (decreased interest in eating), moderate (decreased oral intake), severe(refusal to feed). Drowsiness: mild(increased or prolonged sleeping bouts),moderate(slightly subdued interfering with daily activity),severe(disabling;not interested in usual daily activity). Irritability: mild(easily consolable),moderate(requiring increased attention),severe(Inconsolable; crying cannot be comforted). G4 for all events: ER visit/hospitalisation and classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method. Safety population was used. n=number of participants evaluable for the specified rows.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination 1 (i.e. third dose for Group 1a and fourth dose for Groups 2a and 3a)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 3a: 3 prior doses of BNT162b2
Number of subjects analysed	17	92	68
Units: Percentage of participants
number (confidence interval 95%)
Fever: Any (n=17, 92, 68)	0 (0.0 to 19.5)	8.7 (3.8 to 16.4)	11.8 (5.2 to 21.9)
Fever: >=38.0 to 38.4 deg C (n=17, 92, 68)	0 (0.0 to 19.5)	6.5 (2.4 to 13.7)	2.9 (0.4 to 10.2)
Fever: >38.4 to 38.9 deg C (n=17, 92, 68)	0 (0.0 to 19.5)	1.1 (0.0 to 5.9)	2.9 (0.4 to 10.2)
Fever: >38.9 to 40.0 deg C (n=17, 92, 68)	0 (0.0 to 19.5)	1.1 (0.0 to 5.9)	4.4 (0.9 to 12.4)
Fever: >40.0 deg C (n=17, 92, 68)	0 (0.0 to 19.5)	0 (0.0 to 3.9)	0 (0.0 to 5.3)
Fever: Unknown (n=17, 92, 68)	0 (0.0 to 19.5)	0 (0.0 to 3.9)	1.5 (0.0 to 7.9)
Decreased appetite: Any (n=17, 89, 64)	23.5 (6.8 to 49.9)	20.2 (12.4 to 30.1)	20.3 (11.3 to 32.2)
Decreased appetite: Mild (n=17, 89, 64)	11.8 (1.5 to 36.4)	9.0 (4.0 to 16.9)	14.1 (6.6 to 25.0)
Decreased appetite: Moderate (n=17, 89, 64)	11.8 (1.5 to 36.4)	11.2 (5.5 to 19.7)	6.3 (1.7 to 15.2)
Decreased appetite: Severe (n=17, 89, 64)	0 (0.0 to 19.5)	0 (0.0 to 4.1)	0 (0.0 to 5.6)
Decreased appetite: Grade 4 (n=17, 89, 64)	0 (0.0 to 19.5)	0 (0.0 to 4.1)	0 (0.0 to 5.6)
Drowsiness: Any (n=17, 89, 64)	41.2 (18.4 to 67.1)	20.2 (12.4 to 30.1)	17.2 (8.9 to 28.7)
Drowsiness: Mild (n=17, 89, 64)	35.3 (1 to 61.7)	18.0 (10.6 to 27.5)	15.6 (7.8 to 26.9)
Drowsiness: Moderate (n=17, 89, 64)	5.9 (0.1 to 28.7)	2.2 (0.3 to 7.9)	1.6 (0.0 to 8.4)
Drowsiness: Severe (n=17, 89, 64)	0 (0.0 to 19.5)	0 (0.0 to 4.1)	0 (0.0 to 5.6)
Drowsiness: Grade 4 (n=17, 89, 64)	0 (0.0 to 19.5)	0 (0.0 to 4.1)	0 (0.0 to 5.6)
Irritability: Any (n=17, 89, 64)	64.7 (38.3 to 85.8)	36.0 (26.1 to 46.8)	45.3 (32.8 to 58.3)
Irritability: Mild (n=17, 89, 64)	35.3 (14.2 to 61.7)	16.9 (9.8 to 26.3)	23.4 (13.8 to 35.7)
Irritability: Moderate (n=17, 89, 64)	23.5 (6.8 to 49.9)	18.0 (10.6 to 27.5)	21.9 (12.5 to 34.0)
Irritability: Severe (n=17, 89, 64)	5.9 (0.1 to 28.7)	1.1 (0.0 to 6.1)	0 (0.0 to 5.6)
Irritability: Grade 4 (n=17, 89, 64)	0 (0.0 to 19.5)	0 (0.0 to 4.1)	0 (0.0 to 5.6)

No statistical analyses for this end point

Primary: SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 2 in Participants Aged >=6 months to <2 Years: Group 1a Only

Top of page

End point title

SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 2 in Participants Aged >=6 months to <2 Years: Group 1a Only ^[7] ^[8]

End point description

Systemic events recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after Dose 1. Fever: oral temperature >=38.0 deg C; categorised as >=38.0 to 38.4 deg C, >38.4 to 38.9 deg C, >38.9 to 40.0 deg C and >40.0 deg C. Decreased appetite:mild(decreased interest in eating),moderate(decreased oral intake),severe(refusal to feed).Drowsiness: mild(increased or prolonged sleeping bouts),moderate (slightly subdued interfering with daily activity),severe(disabling;not intereste d in usual daily activity).Irritability:mild (easily consolable), moderate(requiring increased attention),severe(disabling;not interested in usual daily activity).G4 for all events:ER visit/hospitalisation and were classified by investigator or medically qualifi ed person. Events reported as AEs in the CRF within 7 days after vaccination were also included. Exact 95% CI based on Clopper and Pearson method. Safety population.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination 2 (i.e. fourth dose)

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2
Number of subjects analysed	17
Units: Percentage of participants
number (confidence interval 95%)
Fever: Any	11.8 (1.5 to 36.4)
Fever: >=38.0 to 38.4 deg C	0 (0.0 to 19.5)
Fever: >38.4 to 38.9 deg C	0 (0.0 to 19.5)
Fever: >38.9 to 40.0 deg C	11.8 (1.5 to 36.4)
Fever: >40.0 deg C	0 (0.0 to 19.5)
Decreased appetite: Any	17.6 (3.8 to 43.4)
Decreased appetite: Mild	17.6 (3.8 to 43.4)
Decreased appetite: Moderate	0 (0.0 to 19.5)
Decreased appetite: Severe	0 (0.0 to 19.5)
Decreased appetite: Grade 4	0 (0.0 to 19.5)
Drowsiness: Any	11.8 (1.5 to 36.4)
Drowsiness: Mild	11.8 (1.5 to 36.4)
Drowsiness: Moderate	0 (0.0 to 19.5)
Drowsiness: Severe	0 (0.0 to 19.5)
Drowsiness: Grade 4	0 (0.0 to 19.5)
Irritability: Any	52.9 (27.8 to 77.0)
Irritability: Mild	23.5 (6.8 to 49.9)
Irritability: Moderate	23.5 (6.8 to 49.9)
Irritability: Severe	5.9 (0.1 to 28.7)
Irritability: Grade 4	0 (0.0 to 19.5)

No statistical analyses for this end point

Primary: SSB: Percentage of Participants Reporting Adverse Events (AEs) From the First Study Vaccination to 1 Month After Study Vaccination 1 in Participants Aged >=6 Months to <2 Years

Top of page

End point title

SSB: Percentage of Participants Reporting Adverse Events (AEs) From the First Study Vaccination to 1 Month After Study Vaccination 1 in Participants Aged >=6 Months to <2 Years ^[9]

End point description

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 endpoint. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this endpoint. Safety population included all participants who received at least 1 dose of the study intervention.

End point type

Primary

End point timeframe

From study vaccination on Day 1 up to 1 month after study vaccination 1 (i.e. third dose for Group 1a and fourth dose for Group 2a and 3a)

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 3a: 3 prior doses of BNT162b2
Number of subjects analysed	17	92	68
Units: Percentage of participants
number (not applicable)	5.9	10.9	14.7

No statistical analyses for this end point

Primary: SSB: Percentage of Participants Reporting Adverse Events (AEs) From the Second Study Vaccination to 1 Month After Study Vaccination 2 in Participants Aged >=6 Months to <2 Years: Group 1a Only

Top of page

End point title

SSB: Percentage of Participants Reporting Adverse Events (AEs) From the Second Study Vaccination to 1 Month After Study Vaccination 2 in Participants Aged >=6 Months to <2 Years: Group 1a Only ^[10]

End point description

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 2 were reported in this endpoint. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this endpoint. Safety population included all participants who received at least 1 dose of the study intervention.

End point type

Primary

End point timeframe

From study vaccination 2 up to 1 month after study vaccination 2 (i.e. fourth dose)

Notes
[10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2
Number of subjects analysed	17
Units: Percentage of participants
number (not applicable)	5.9

No statistical analyses for this end point

Primary: SSB: Percentage of Participants Reporting Serious Adverse Events (SAEs) From the Study Vaccination to 6 Months After Last Study Vaccination in Participants Aged >=6 Months to <2 Years

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End point title

SSB: Percentage of Participants Reporting Serious Adverse Events (SAEs) From the Study Vaccination to 6 Months After Last Study Vaccination in Participants Aged >=6 Months to <2 Years ^[11]

End point description

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 hospitalisation or prolongation of existing hospitalisation. Safety population included all participants who received at least 1 dose of the study intervention.

End point type

Primary

End point timeframe

From study vaccination up to 6 months after last study vaccination

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 3a: 3 prior doses of BNT162b2
Number of subjects analysed	17	92	68
Units: Percentage of participants
number (not applicable)	0	0	0

No statistical analyses for this end point

Primary: SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 2 in Participants Aged >=2 to <5 Years: Group 1b Only

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End point title

SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 2 in Participants Aged >=2 to <5 Years: Group 1b Only ^[12] ^[13]

End point description

Local reactions recorded by participants/parents/legal guardians in e-diary.Redness & swelling recorded in mdu converted to cm.1 mdu=0.5 cm&graded mild:(>0.5 to 2.0cm),moderate:>2.0 to 7.0cm,severe:>7.0 cm,G4: necrosis/exfoliative dermatitis(redness) & necrosis(swelling). Pain at injection site graded mild:did not interfere with daily activity,moderate:interfered with daily activity, severe: prevented daily activity & G4: ER ]visit/hospitalisation.G4 classified by investigator/medically qualified person.Percentage of participants with local reactions within 7days after study vaccination and associated 2-sided 95% CI based on Clopper and Pearson method.Safety population=all participants receiving at least 1 dose of study intervention. Number of participants analyzed= participants evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination 2 (i.e third dose for Group 1b)

Notes
[12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	12
Units: Percentage of participants
number (confidence interval 95%)
Redness: Any	0 (0.0 to 28.5)
Redness: Mild	0 (0.0 to 28.5)
Redness: Moderate	0 (0.0 to 28.5)
Redness: Severe	0 (0.0 to 28.5)
Redness: Grade 4	0 (0.0 to 28.5)
Swelling: Any	0 (0.0 to 28.5)
Swelling: Mild	0 (0.0 to 28.5)
Swelling: Moderate	0 (0.0 to 28.5)
Swelling: Severe	0 (0.0 to 28.5)
Swelling: Grade 4	0 (0.0 to 28.5)
Pain at the injection site: Any	9.1 (0.2 to 41.3)
Pain at the injection site: Mild	9.1 (0.2 to 41.3)
Pain at the injection site: Moderate	0 (0.0 to 28.5)
Pain at the injection site: Severe	0 (0.0 to 28.5)
Pain at the injection site: Grade 4	0 (0.0 to 28.5)

No statistical analyses for this end point

Primary: SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 1 in Participants Aged >=2 to <5 Years

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End point title

SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 1 in Participants Aged >=2 to <5 Years ^[14] ^[15]

End point description

Local reactions recorded by participants/parents/legal guardians in e-diary.Redness & swelling recorded in mdu converted to cm.1 mdu=0.5 cm&graded mild:(>0.5 to 2.0cm),moderate:>2.0 to 7.0cm,severe:>7.0 cm,G4: necrosis/exfoliative dermatitis(redness)&necrosis(swelling).Pain at injection site graded mild:did not interfere with daily activity,moderate:interfered with daily activity, severe: prevented daily activity & G4: ER ]visit/hospitalisation.G4 classifi ed by investigator/medically qualifi ed person.Percentage of participants with local reactions within 7days after study vaccination and associated 2-sided 95% CI based on Clopper and Pearson method.Safety population=all participants receiving at least 1 dose of study intervention. Number of participants analyzed= participants evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination 1 (i.e. third dose for Group 1b and fourth dose for Groups 2b and 3b)

Notes
[14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1b: 2 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2	SSB: Group 3b: 3 prior doses of BNT162b2
Number of subjects analysed	13	218	986
Units: Percentage of participants
number (confidence interval 95%)
Redness: Any	7.7 (0.2 to 36.0)	6.4 (3.6 to 10.5)	10.1 (8.3 to 12.2)
Redness: Mild	0 (0.0 to 24.7)	5.5 (2.9 to 9.4)	8.8 (7.1 to 10.8)
Redness: Moderate	7.7 (0.2 to 36.0)	0.9 (0.1 to 3.3)	1.3 (0.7 to 2.2)
Redness: Severe	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
Redness: Grade 4	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
Swelling: Any	7.7 (0.2 to 36.0)	4.1 (1.9 to 7.7)	4.0 (2.8 to 5.4)
Swelling: Mild	7.7 (0.2 to 36.0)	3.7 (1.6 to 7.1)	3.4 (2.4 to 4.8)
Swelling: Moderate	0 (0.0 to 24.7)	0.5 (0.0 to 2.5)	0.5 (0.2 to 1.2)
Swelling: Severe	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
Swelling: Grade 4	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
Pain at the injection site: Any	30.8 (9.1 to 61.4)	30.3 (24.3 to 36.8)	30.3 (27.5 to 33.3)
Pain at the injection site: Mild	30.8 (9.1 to 61.4)	28.4 (22.6 to 34.9)	27.9 (25.1 to 30.8)
Pain at the injection site: Moderate	0 (0.0 to 24.7)	1.8 (0.5 to 4.6)	2.5 (1.6 to 3.6)
Pain at the injection site: Severe	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
Pain at the injection site: Grade 4	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)

No statistical analyses for this end point

Primary: SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 1 in Participants Aged >=2 to <5 Years

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End point title

SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 1 in Participants Aged >=2 to <5 Years ^[16] ^[17]

End point description

Systemic events recorded by participants/parents/legal guardians in e-diary. Fever: oral temperature >= 38.0 deg C and categorised 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,new/worsened muscle pain&new/worsened joint pain:mild:did not interfere with activity,moderate:some interference with activity&severe: prevented daily routine activity.Vomiting:mild: 1-2 times in 24h,moderate:>2 times in 24h,severe:required intravenous hydration.Diarrhea:mild: 2-3 loose stools in 24h,moderate:4-5 loose stools in 24h&severe:6 or more loose stools in 24h.Except fever,G4=ER visit/hospitalisation.G4 events classified by investigator/medically qualified person. Exact 95% CI based on Clopper & Pearson method.Safety population=all participants receiving at least 1 dose of study intervention.N= participants evaluable for this endpoint.n=participants evaluable for specified rows.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination 1 (i.e. third dose for Group 1b and fourth dose for Groups 2b and 3b)

Notes
[16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1b: 2 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2	SSB: Group 3b: 3 prior doses of BNT162b2
Number of subjects analysed	13	218	986
Units: Percentage of participants
number (confidence interval 95%)
Fever:Any (n=13, 218, 986)	0 (0.0 to 24.7)	6.9 (3.9 to 11.1)	5.3 (4.0 to 6.9)
Fever: >=38.0 to 38.4 deg C (n=13, 218, 986)	0 (0.0 to 24.7)	1.8 (0.5 to 4.6)	1.5 (0.9 to 2.5)
Fever: >38.4 to 38.9 deg C (n=13, 218, 986)	0 (0.0 to 24.7)	3.2 (1.3 to 6.5)	2.0 (1.2 to 3.1)
Fever: >38.9 to 40.0 deg C (n=13, 218, 986)	0 (0.0 to 24.7)	1.4 (0.3 to 4.0)	1.4 (0.8 to 2.4)
Fever: >40.0 deg C (n=13, 218, 986)	0 (0.0 to 24.7)	0.5 (0.0 to 2.5)	0.2 (0.0 to 0.7)
Fever: Unknown ((n=13, 218, 986)	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0.1 (0.0 to 0.6)
Fatigue: Any (n=13, 217, 976)	30.8 (9.1 to 61.4)	31.3 (25.2 to 38.0)	29.0 (26.2 to 32.0)
Fatigue: Mild (n=13, 217, 976)	15.4 (1.9 to 45.4)	17.5 (12.7 to 23.2)	17.8 (15.5 to 20.4)
Fatigue: Moderate (n=13, 217, 976)	15.4 (1.9 to 45.4)	12.4 (8.4 to 17.6)	10.7 (8.8 to 12.8)
Fatigue: Severe (n=13, 217, 976)	0 (0.0 to 24.7)	1.4 (0.3 to 4.0)	0.5 (0.2 to 1.2)
Fatigue: Grade 4 (n=13, 217, 976)	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
Headache: Any (n=13, 217, 976)	7.7 (0.2 to 36.0)	4.1 (1.9 to 7.7)	4.4 (3.2 to 5.9)
Headache: Mild (n=13, 217, 976)	7.7 (0.2 to 36.0)	2.3 (0.8 to 5.3)	3.7 (2.6 to 5.1)
Headache: Moderate (n=13, 217, 976)	0 (0.0 to 24.7)	1.4 (0.3 to 4.0)	0.7 (0.3 to 1.5)
Headache: Severe (n=13, 217, 976)	0 (0.0 to 24.7)	0.5 (0.0 to 2.5)	0 (0.0 to 0.4)
Headache: Grade 4 (n=13, 217, 976)	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
Chills: Any (n=13, 217, 976)	0 (0.0 to 24.7)	4.6 (2.2 to 8.3)	2.5 (1.6 to 3.6)
Chills: Mild (n=13, 217, 976)	0 (0.0 to 24.7)	3.2 (1.3 to 6.5)	1.8 (1.1 to 2.9)
Chills: Moderate (n=13, 217, 976)	0 (0.0 to 24.7)	1.4 (0.3 to 4.0)	0.6 (0.2 to 1.3)
Chills: Severe (n=13, 217, 976)	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
Chills: Grade 4 (n=13, 217, 976)	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
Vomiting: Any (n=13, 217, 976)	7.7 (0.2 to 36.0)	5.1 (2.6 to 8.9)	4.8 (3.6 to 6.4)
Vomiting: Mild (n=13, 217, 976)	7.7 (0.2 to 36.0)	3.2 (1.3 to 6.5)	4.0 (2.9 to 5.4)
Vomiting: Moderate (n=13, 217, 976)	0 (0.0 to 24.7)	1.8 (0.5 to 4.7)	0.8 (0.4 to 1.6)
Vomiting: Severe (n=13, 217, 976)	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
Vomiting: Grade 4 (n=13, 217, 976)	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
Diarrhea: Any (n=13, 217, 976)	0 (0.0 to 24.7)	5.1 (2.6 to 8.9)	7.0 (5.5 to 8.7)
Diarrhea: Mild (n=13, 217, 976)	0 (0.0 to 24.7)	4.1 (1.9 to 7.7)	6.0 (4.6 to 7.7)
Diarrhea: Moderate (n=13, 217, 976)	0 (0.0 to 24.7)	0.9 (0.1 to 3.3)	0.8 (0.4 to 1.6)
Diarrhea: Severe (n=13, 217, 976)	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0.1 (0.0 to 0.6)
Diarrhea: Grade 4 (n=13, 217, 976)	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
New or worsened muscle pain:Any(n=13,217,976)	0 (0.0 to 24.7)	3.2 (1.3 to 6.5)	2.0 (1.3 to 3.1)
New or worsened muscle pain:Mild(n=13,217,976)	0 (0.0 to 24.7)	2.3 (0.8 to 5.3)	1.2 (0.6 to 2.1)
New or worsened muscle pain:Moderate(n=13,217,976)	0 (0.0 to 24.7)	0.9 (0.1 to 3.3)	0.8 (0.4 to 1.6)
New or worsened muscle pain:Severe(n=13,217,976)	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
New or worsened muscle pain:Grade4(n=13,217,976)	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
New or worsened joint pain:Any(n=13,217,976)	0 (0.0 to 24.7)	0.9 (0.1 to 3.3)	0.9 (0.4 to 1.7)
New or worsened joint pain:Mild(n=13,217,976)	0 (0.0 to 24.7)	0.9 (0.1 to 3.3)	0.7 (0.3 to 1.5)
New or worsened joint pain:Moderate(n=13,217,976)	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0.2 (0.0 to 0.7)
New or worsened joint pain:Severe(n=13,217,976)	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)
New or worsened joint pain:Grade 4(n=13,217,976)	0 (0.0 to 24.7)	0 (0.0 to 1.7)	0 (0.0 to 0.4)

No statistical analyses for this end point

Primary: SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 2 in Participants Aged >=2 to <5 Years: Group 1b Only

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End point title

SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 2 in Participants Aged >=2 to <5 Years: Group 1b Only ^[18] ^[19]

End point description

Systemic events recorded by participants/parents/legal guardians in e-diary. Fever: oral temperature >= 38.0 deg C and categorised 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,new/worsened muscle pain&new/worsened joint pain:mild:did not interfere with activity,moderate:some interference with activity&severe: prevented daily routine activity.Vomiting:mild: 1-2 times in 24h,moderate:>2 times in 24h,severe:required intravenous hydration.Diarrhea:mild: 2-3 loose stools in 24h,moderate:4-5 loose stools in 24h & severe:6 or more loose stools in 24h.Except fever,G4=ER visit/hospitalisation.G4 events classified by investigator/medically qualified person. Exact 95% CI based on Clopper & Pearson method.Safety population=all participants receiving at least 1 dose of study intervention.N= participants evaluable for this endpoint.n=participants evaluable for specified rows.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination 2 (i.e third dose for Group 1b)

Notes
[18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	12
Units: Percentage of participants
number (confidence interval 95%)
Fever: >= 38.0 deg C (n=11)	0 (0.0 to 28.5)
Fever: 38.0 to 38.4 deg C (n=11)	0 (0.0 to 28.5)
Fever: >38.4 to 38.9 deg C (n=11)	0 (0.0 to 28.5)
Fever: >38.9 to 40.0 deg C (n=11)	0 (0.0 to 28.5)
Fever: >40.0 deg C (n=11)	0 (0.0 to 28.5)
Fatigue: Any (n=12)	33.3 (9.9 to 65.1)
Fatigue: Mild (n=12)	16.7 (2.1 to 48.4)
Fatigue: Moderate (n=12)	16.7 (2.1 to 48.4)
Fatigue: Severe (n=12)	0 (0.0 to 26.5)
Fatigue: Grade 4 (n=12)	0 (0.0 to 26.5)
Headache: Any (n=11)	0 (0.0 to 28.5)
Headache: Mild (n=11)	0 (0.0 to 28.5)
Headache: Moderate (n=11)	0 (0.0 to 28.5)
Headache: Severe (n=11)	0 (0.0 to 28.5)
Headache: Grade 4 (n=11)	0 (0.0 to 28.5)
Chills: Any (n=11)	0 (0.0 to 28.5)
Chills: Mild (n=11)	0 (0.0 to 28.5)
Chills: Moderate (n=11)	0 (0.0 to 28.5)
Chills: Severe (n=11)	0 (0.0 to 28.5)
Chills: Grade 4 (n=11)	0 (0.0 to 28.5)
Vomiting: Any (n=11)	9.1 (0.2 to 41.3)
Vomiting: Mild (n=11)	9.1 (0.2 to 41.3)
Vomiting: Moderate (n=11)	0 (0.0 to 28.5)
Vomiting: Severe (n=11)	0 (0.0 to 28.5)
Vomiting: Grade 4 (n=11)	0 (0.0 to 28.5)
Diarrhea: Any (n=11)	9.1 (0.2 to 41.3)
Diarrhea: Mild (n=11)	9.1 (0.2 to 41.3)
Diarrhea: Moderate (n=11)	0 (0.0 to 28.5)
Diarrhea: Severe (n=11)	0 (0.0 to 28.5)
Diarrhea: Grade 4 (n=11)	0 (0.0 to 28.5)
New or worsened muscle pain: Any (n=11)	0 (0.0 to 28.5)
New or worsened muscle pain: Mild (n=11)	0 (0.0 to 28.5)
New or worsened muscle pain: Moderate (n=11)	0 (0.0 to 28.5)
New or worsened muscle pain: Severe (n=11)	0 (0.0 to 28.5)
New or worsened muscle pain: Grade 4 (n=11)	0 (0.0 to 28.5)
New or worsened joint pain: Any (n=11)	0 (0.0 to 28.5)
New or worsened joint pain: Mild (n=11)	0 (0.0 to 28.5)
New or worsened joint pain: Moderate (n=11)	0 (0.0 to 28.5)
New or worsened joint pain: Severe (n=11)	0 (0.0 to 28.5)
New or worsened joint pain: Grade 4 (n=11)	0 (0.0 to 28.5)

No statistical analyses for this end point

Primary: SSB: Percentage of Participants Reporting AEs From the First Study Vaccination to 1 Month After Study Vaccination 1 in Participants Aged >=2 to <5 Years

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End point title

SSB: Percentage of Participants Reporting AEs From the First Study Vaccination to 1 Month After Study Vaccination 1 in Participants Aged >=2 to <5 Years ^[20] ^[21]

End point description

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 endpoint.Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this endpoint. Safety population included all participants who received at least 1 dose of the study intervention.

End point type

Primary

End point timeframe

From study vaccination on Day 1 up to 1 month after study vaccination 1 (i.e. third dose for Group 1b and fourth dose for Groups 2b and 3b)

Notes
[20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1b: 2 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2	SSB: Group 3b: 3 prior doses of BNT162b2
Number of subjects analysed	13	218	989
Units: Percentage of participants
number (not applicable)	0	4.6	6.6

No statistical analyses for this end point

Primary: SSB: Percentage of Participants Reporting AEs From the Second Study Vaccination to 1 Month After Study Vaccination 2 in Participants Aged >=2 to <5 Years: Group 1b Only

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End point title

SSB: Percentage of Participants Reporting AEs From the Second Study Vaccination to 1 Month After Study Vaccination 2 in Participants Aged >=2 to <5 Years: Group 1b Only ^[22] ^[23]

End point description

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 endpoint. 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 endpoint. Safety population included all participants who received at least 1 dose of the study intervention.N=participants evaluable for this endpoint.This endpoint is reported for Group 1b only as only participants from Group 1b received two vaccinations in the study.

End point type

Primary

End point timeframe

From study vaccination 2 up to 1 month after study vaccination 2

Notes
[22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	12
Units: Percentage of participants
number (confidence interval 95%)	8.3 (0.2 to 38.5)

No statistical analyses for this end point

Primary: SSB: Percentage of Participants Reporting SAEs From the First Study Vaccination to 6 Months After Last Study Vaccination in Participants Aged >=2 to <5 Years

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End point title

SSB: Percentage of Participants Reporting SAEs From the First Study Vaccination to 6 Months After Last Study Vaccination in Participants Aged >=2 to <5 Years ^[24] ^[25]

End point description

End point type

Primary

End point timeframe

From first study vaccination on Day 1 up to 6 months after last study vaccination

Notes
[24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1b: 2 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2	SSB: Group 3b: 3 prior doses of BNT162b2
Number of subjects analysed	12	218	989
Units: Percentage of participants
number (not applicable)	0	0	0.4

No statistical analyses for this end point

Primary: SSB: GMR Based on Geometric Mean Titers of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‑CoV‑2) Omicron (BA.4/BA.5)–Neutralizing Titers at 1 Month After Dose 4 for Group 2 and at 1 Month After Dose 3 for C4591007 Phase 2/3 Participants

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End point title

SSB: GMR Based on Geometric Mean Titers of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‑CoV‑2) Omicron (BA.4/BA.5)–Neutralizing Titers at 1 Month After Dose 4 for Group 2 and at 1 Month After Dose 3 for C4591007 Phase 2/3 Participants ^[26]

End point description

GMTs and the corresponding 2-sided CIs were calculated by exponentiating the least square means and the corresponding CIs based on analysis of log-transformed assay results using a linear regression model with baseline log-transformed neutralizing titers,postbaseline infection status& vaccine group as covariates.Assay results below the LLOQ were set to 0.5*LLOQ.Evaluable immunogenicity population included all eligible participants who received the study intervention to which they were assigned,had atleast one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination,had no other important protocol deviations as determined by clinician.Results are presented for per-protocol subset which included random sample of 240 participants selected from the full group &comprised the same percentages of participants in each age group and baseline SARS-CoV-2 infection status group as the full group.'N'=participants evaluable.

End point type

Primary

End point timeframe

1 month after Dose 4 for Group 2 and 1 month after Dose 3 for C4591007 control arm

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2	SSB Historical cohort:C4591007 BNT162b2 >=6 months to<2 years	SSB Historical cohort: C4591007 BNT162b2 3 mcg
Number of subjects analysed	62	161	71	167
Units: Titers
geometric mean (confidence interval 95%)	1664.4 (1339.3 to 2068.3)	1920.7 (1661.9 to 2219.8)	1031.3 (842.0 to 1263.3)	901.8 (782.4 to 1039.5)

Geometric Mean Ratio

Statistical analysis description

GMRs and 2-sided CIs were calculated by exponentiating the diff erence of LSMeans for the assay and the corresponding CIs based on analysis of log-transformed assay results using a linear regression model with baseline log-transformed neutralizing titers, postbaseline infection status, age group and vaccine group as covariates.

Comparison groups

SSB: Group 2b: 3 prior doses of BNT162b2 v SSB Historical cohort: C4591007 BNT162b2 3 mcg

Number of subjects included in analysis

328

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Geometric Mean Ratio

Point estimate

2.13

Confidence interval

level

95%

sides

2-sided

lower limit

1.73

upper limit

2.62

Geometric Mean Ratio

Statistical analysis description

GMRs and 2-sided CIs were calculated by exponentiating the difference of LSMeans for the assay and the corresponding CIs based on analysis of log-transformed assay results using a linear regression model with baseline log-transformed neutralizing titers, postbaseline infection status, age group and vaccine group as covariates.

Comparison groups

SSB: Group 2a: 3 prior doses of BNT162b2 v SSB Historical cohort:C4591007 BNT162b2 >=6 months to<2 years

Number of subjects included in analysis

133

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Geometric Mean Ratio

Point estimate

1.61

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

2.18

Primary: SSB: Percentage of Participants With Seroresponse to the Omicron (BA.4/BA.5)–Strain at 1 Month After Dose 4 for Group 2 and at 1 Month After Dose 3 for C4591007 Phase 2/3 Participants

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End point title

SSB: Percentage of Participants With Seroresponse to the Omicron (BA.4/BA.5)–Strain at 1 Month After Dose 4 for Group 2 and at 1 Month After Dose 3 for C4591007 Phase 2/3 Participants ^[27]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before Dose 4 for C4591048 Substudy B Group 2 and before Dose 3 for C4591007). If the baseline measurement was below the lower limit of quantification (LLOQ), the postvaccination assay result of >= 4*LLOQ was considered a seroresponse. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Percentage of participants achieving seroresponse at 1 month after study vaccination was reported in this endpoint. Evaluable immunogenicity population was analyzed. Results were presented for per-protocol subset which included a random sample of 240 participants selected from the full group and comprised of the same percentage of participants in each age group and baseline SARS-CoV-2 infection status group as the full group.'N'=participants evaluable for this endpoint.

End point type

Primary

End point timeframe

1 month after Dose 4 for Group 2 and 1 month after Dose 3 for C4591007 control arm

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2	SSB Historical cohort:C4591007 BNT162b2 >=6 months to<2 years	SSB Historical cohort: C4591007 BNT162b2 3 mcg
Number of subjects analysed	62	161	71	167
Units: Percentage of participants
number (confidence interval 95%)	54.8 (41.7 to 67.5)	71.4 (63.8 to 78.3)	42.3 (30.6 to 54.6)	53.9 (46.0 to 61.6)

Percentages of Participants With Seroresponse

Statistical analysis description

Adjusted difference in proportion based on the Miettinen and Nurminen method stratified by baseline neutralizing titer category (<median, ≥median), expressed as a percentage (bivalent BNT162b2 [original/Omi BA.4/BA.5] 3 mcg - BNT162b2 3 mcg).

Comparison groups

SSB: Group 2a: 3 prior doses of BNT162b2 v SSB Historical cohort:C4591007 BNT162b2 >=6 months to<2 years

Number of subjects included in analysis

133

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[28]

Method

Parameter type

Percentage Difference

Point estimate

16.24

Confidence interval

level

95%

sides

2-sided

lower limit

0.8

upper limit

31.67

Notes
[28] - Noninferiority was established if the lower bound of the 2-sided 95% CI for the difference in percentage was greater than -5%.

Percentages of Participants With Seroresponse

Statistical analysis description

Comparison groups

SSB: Group 2b: 3 prior doses of BNT162b2 v SSB Historical cohort: C4591007 BNT162b2 3 mcg

Number of subjects included in analysis

328

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[29]

Method

Parameter type

Percentage Difference

Point estimate

21.37

Confidence interval

level

95%

sides

2-sided

lower limit

11.59

upper limit

31.15

Notes
[29] - Noninferiority was established if the lower bound of the 2-sided 95% CI for the difference in percentage was greater than -5%.

Primary: SSC: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination in Participants Aged >=6 Months to <2 Years

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End point title

SSC: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination in Participants Aged >=6 Months to <2 Years ^[30] ^[31]

End point description

Local reactions were collected in e-diary or during unscheduled clinical assessments from Day 1 to Day 7 after study vaccination. Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and were graded as mild (>=0.5 to 2.0 cm), moderate (>2.0 to 7.0 cm), severe(>7.0 cm) and G4 (necrosis [redness and swelling] or exfoliative dermatitis [redness]). Tenderness at injection site was graded as mild (hurts if gently touched), moderate (hurts if gently touched with crying), severe (causes limitation of limb movement) & G4 ER visit or hospitalisation. G4 were classified by investigator or medically qualified person. Percentage of participants with local reactions within 7 days after study vaccination and associated 2-sided 95% CI based on Clopper and Pearson method is reported. Safety population=all participants receiving at least 1 dose of study intervention.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination

Notes
[30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.

End point values	SSC: Group 1a: 3 prior doses of BNT162b2	SSC: Group 1b: 3 prior doses of BNT162b2
Number of subjects analysed	17	19
Units: Percentage of participants
number (confidence interval 95%)
Redness: Any	23.5 (6.8 to 49.9)	21.1 (6.1 to 45.6)
Redness: Mild	17.6 (3.8 to 43.4)	21.1 (6.1 to 45.6)
Redness: Moderate	5.9 (0.1 to 28.7)	0 (0.0 to 17.6)
Redness: Severe	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Redness: Grade 4	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Swelling: Any	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Swelling: Mild	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Swelling: Moderate	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Swelling: Severe	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Swelling: Grade 4	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Tenderness at the injection site: Any	5.9 (0.1 to 28.7)	15.8 (3.4 to 39.6)
Tenderness at the injection site: Mild	5.9 (0.1 to 28.7)	15.8 (3.4 to 39.6)
Tenderness at the injection site: Moderate	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Tenderness at the injection site: Severe	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Tenderness at the injection site: Grade 4	0 (0.0 to 19.5)	0 (0.0 to 17.6)

No statistical analyses for this end point

Primary: SSC: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination in Participants Aged >=6 Months to <2 Years

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End point title

SSC: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination in Participants Aged >=6 Months to <2 Years ^[32] ^[33]

End point description

Systemic events recorded in an e-diary and at unscheduled clinical assessments from Day 1 to 7 after study vaccination.Fever:oral temperature >=38.0 deg C categorised as >=38.0 to 38.4 deg C,>38.4 to 38.9 deg C, >38.9 to 40.0 deg C & >40.0 deg C.Decreased appetite:mild(decreased interest in eating),moderate(decreased oral intake),severe(refusal to feed).Drowsiness:mild(increased or prolonged sleeping bouts),moderate(slightly subdued interfering with daily activity),severe(disabling;not interested in usual daily activity).Irritability:mild(easily consolable),moderate(requiring increased attention),severe(disabling;not interested in usual daily activity).G4 for all events except fever:ER visit/hospitalisation & were classified by investigator or medically qualified person. Events reported as AEs in the CRF within 7 days after vaccination were also included.Exact 95% CI based on Clopper and Pearson method.Safety population=all participants receiving at least 1 dose of study intervention.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination

Notes
[32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.

End point values	SSC: Group 1a: 3 prior doses of BNT162b2	SSC: Group 1b: 3 prior doses of BNT162b2
Number of subjects analysed	17	19
Units: Percentage of participants
number (confidence interval 95%)
Fever:Any	17.6 (3.8 to 43.4)	5.3 (0.1 to 26.0)
Fever: >=38.0 to 38.4 deg C	11.8 (1.5 to 36.4)	0 (0.0 to 17.6)
Fever: >38.4 to 38.9 deg C	5.9 (0.1 to 28.7)	5.3 (0.1 to 26.0)
Fever: >38.9 to 40.0 deg C	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Fever: >40.0 deg C	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Decreased appetite: Any	23.5 (6.8 to 49.9)	15.8 (3.4 to 39.6)
Decreased appetite: Mild	23.5 (6.8 to 49.9)	15.8 (3.4 to 39.6)
Decreased appetite: Moderate	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Decreased appetite: Severe	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Decreased appetite: Grade 4	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Drowsiness: Any	29.4 (10.3 to 56.0)	26.3 (9.1 to 51.2)
Drowsiness: Mild	17.6 (3.8 to 43.4)	21.1 (6.1 to 45.6)
Drowsiness: Moderate	11.8 (1.5 to 36.4)	5.3 (0.1 to 26.0)
Drowsiness: Severe	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Drowsiness: Grade 4	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Irritability: Any	47.1 (23.0 to 72.2)	73.7 (48.8 to 90.9)
Irritability: Mild	29.4 (10.3 to 56.0)	21.1 (6.1 to 45.6)
Irritability: Moderate	17.6 (3.8 to 43.4)	52.6 (28.9 to 75.6)
Irritability: Severe	0 (0.0 to 19.5)	0 (0.0 to 17.6)
Irritability: Grade 4	0 (0.0 to 19.5)	0 (0.0 to 17.6)

No statistical analyses for this end point

Primary: SSC: Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination in Participants Aged >=6 Months to <2 Years

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End point title

SSC: Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination in Participants Aged >=6 Months to <2 Years ^[34] ^[35]

End point description

End point type

Primary

End point timeframe

From study vaccination on Day 1 up to 1 month after study vaccination

Notes
[34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.

End point values	SSC: Group 1a: 3 prior doses of BNT162b2	SSC: Group 1b: 3 prior doses of BNT162b2
Number of subjects analysed	17	19
Units: Percentage of participants
number (not applicable)	11.8	15.8

No statistical analyses for this end point

Primary: SSC: Percentage of Participants Reporting Serious Adverse Events (SAEs) Within 6 Months After Study Vaccination in Participants Aged >=6 Months to <2 Years

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End point title

SSC: Percentage of Participants Reporting Serious Adverse Events (SAEs) Within 6 Months After Study Vaccination in Participants Aged >=6 Months to <2 Years ^[36] ^[37]

End point description

End point type

Primary

End point timeframe

From study vaccination on Day 1 up to 6 months after study vaccination

Notes
[36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.

End point values	SSC: Group 1a: 3 prior doses of BNT162b2	SSC: Group 1b: 3 prior doses of BNT162b2
Number of subjects analysed	17	19
Units: Percentage of participants
number (not applicable)	0	0

No statistical analyses for this end point

Primary: SSC: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination in Participants Aged >=2 to <5 Years

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End point title

SSC: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination in Participants Aged >=2 to <5 Years ^[38] ^[39]

End point description

Local reactions recorded by participants/parents/legal guardians in e-diary.Redness & swelling recorded in mdu converted to cm.1 mdu=0.5 cm&graded mild:(>0.5 to 2.0cm),moderate:>2.0 to 7.0cm,severe:>7.0 cm,G4: necrosis/exfoliative dermatitis(redness) & necrosis(swelling).Pain at injection site graded mild:did not interfere with daily activity,moderate:interfered with daily activity, severe: prevented daily activity & G4: ER ]visit/hospitalisation.G4 classifi ed by investigator/medically qualifi ed person.Percentage of participants with local reactions within 7days after study vaccination and associated 2-sided 95% CI based on Clopper and Pearson method.Safety population=all participants receiving at least 1 dose of study intervention. Number of subjects analyzed= participants evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination

Notes
[38] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.

End point values	SSC: Group 2a: 3 prior doses of BNT162b2	SSC: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	32	30
Units: Percentage of participants
number (confidence interval 95%)
Redness: Any	6.3 (0.8 to 20.8)	3.3 (0.1 to 17.2)
Redness: Mild	6.3 (0.8 to 20.8)	3.3 (0.1 to 17.2)
Redness: Moderate	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Redness: Severe	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Redness: Grade 4	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Swelling: Any	6.3 (0.8 to 20.8)	0 (0.0 to 11.6)
Swelling: Mild	6.3 (0.8 to 20.8)	0 (0.0 to 11.6)
Swelling: Moderate	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Swelling: Severe	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Swelling: Grade 4	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Pain at the injection site: Any	31.3 (16.1 to 50.0)	26.7 (12.3 to 45.9)
Pain at the injection site: Mild	28.1 (13.7 to 46.7)	26.7 (12.3 to 45.9)
Pain at the injection site: Moderate	3.1 (0.1 to 16.2)	0 (0.0 to 11.6)
Pain at the injection site: Severe	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Pain at the injection site: Grade 4	0 (0.0 to 10.9)	0 (0.0 to 11.6)

No statistical analyses for this end point

Primary: SSC: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination in Participants Aged >=2 to <5 Years

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End point title

SSC: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination in Participants Aged >=2 to <5 Years ^[40] ^[41]

End point description

Systemic events recorded by participants/parents/legal guardians in e-diary. Fever: oral temperature >= 38.0 deg C and categorised 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,new/worsened muscle pain & new/worsened joint pain:mild:did not interfere with activity,moderate:some interference with activity&severe: prevented daily routine activity.Vomiting:mild: 1-2 times in 24h,moderate:>2 times in 24h,severe:required intravenous hydration.Diarrhea:mild: 2-3 loose stools in 24h,moderate:4-5 loose stools in 24h&severe:6 or more loose stools in 24h.Except fever,G4=ER visit/hospitalisation.G4 events classified by investigator/medically qualified person. Exact 95% CI based on Clopper & Pearson method.Safety population=all participants receiving at least 1 dose of study intervention.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination

Notes
[40] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.

End point values	SSC: Group 2a: 3 prior doses of BNT162b2	SSC: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	32	30
Units: Percentage of participants
number (confidence interval 95%)
Fever: Any	25.0 (11.5 to 43.4)	10.0 (2.1 to 26.5)
Fever:38.0 to 38.4 deg C	6.3 (0.8 to 20.8)	6.7 (0.8 to 22.1)
Fever: >38.4 to 38.9 deg C	12.5 (3.5 to 29.0)	0 (0.0 to 11.6)
Fever: >38.9 to 40.0 deg C	6.3 (0.8 to 20.8)	3.3 (0.1 to 17.2)
Fever: >40.0 deg C	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Fatigue: Any	40.6 (23.7 to 59.4)	36.7 (19.9 to 56.1)
Fatigue: Mild	12.5 (3.5 to 29.0)	23.3 (9.9 to 42.3)
Fatigue: Moderate	21.9 (9.3 to 40.0)	13.3 (3.8 to 30.7)
Fatigue: Severe	6.3 (0.8 to 20.8)	0 (0.0 to 11.6)
Fatigue: Grade 4	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Headache: Any	12.5 (3.5 to 29.0)	3.3 (0.1 to 17.2)
Headache: Mild	6.3 (0.8 to 20.8)	3.3 (0.1 to 17.2)
Headache: Moderate	6.3 (0.8 to 20.8)	0 (0.0 to 11.6)
Headache: Severe	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Headache: Grade 4	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Chills: Any	12.5 (3.5 to 29.0)	3.3 (0.1 to 17.2)
Chills: Mild	9.4 (2.0 to 25.0)	0 (0.0 to 11.6)
Chills: Moderate	3.1 (0.1 to 16.2)	3.3 (0.1 to 17.2)
Chills: Severe	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Chills: Grade 4	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Vomiting: Any	9.4 (2.0 to 25.0)	6.7 (0.8 to 22.1)
Vomiting: Mild	6.3 (0.8 to 20.8)	6.7 (0.8 to 22.1)
Vomiting: Moderate	3.1 (0.1 to 16.2)	0 (0.0 to 11.6)
Vomiting: Severe	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Vomiting: Grade 4	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Diarrhea: Any	6.3 (0.8 to 20.8)	3.3 (0.1 to 17.2)
Diarrhea: Mild	3.1 (0.1 to 16.2)	0 (0.0 to 11.6)
Diarrhea: Moderate	3.1 (0.0 to 10.9)	3.3 (0.1 to 17.2)
Diarrhea: Severe	0 (0.0 to 10.9)	0 (0.0 to 11.6)
Diarrhea: Grade 4	0 (0.0 to 10.9)	0 (0.0 to 11.6)
New or worsened muscle pain: Any	9.4 (2.0 to 25.0)	6.7 (0.8 to 22.1)
New or worsened muscle pain: Mild	6.3 (0.8 to 20.8)	3.3 (0.1 to 17.2)
New or worsened muscle pain: Moderate	3.1 (0.1 to 16.2)	3.3 (0.1 to 17.2)
New or worsened muscle pain: Severe	0 (0.0 to 10.9)	0 (0.0 to 11.6)
New or worsened muscle pain: Grade 4	0 (0.0 to 10.9)	0 (0.0 to 11.6)
New or worsened joint pain: Any	0 (0.0 to 10.9)	0 (0.0 to 11.6)
New or worsened joint pain: Mild	0 (0.0 to 10.9)	0 (0.0 to 11.6)
New or worsened joint pain: Moderate	0 (0.0 to 10.9)	0 (0.0 to 11.6)
New or worsened joint pain: Severe	0 (0.0 to 10.9)	0 (0.0 to 11.6)
New or worsened joint pain: Grade 4	0 (0.0 to 10.9)	0 (0.0 to 11.6)

No statistical analyses for this end point

Primary: SSC: Percentage of Participants Reporting AEs Within 1 Month After Study Vaccination in Participants Aged >=2 to <5 Years

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End point title

SSC: Percentage of Participants Reporting AEs Within 1 Month After Study Vaccination in Participants Aged >=2 to <5 Years ^[42] ^[43]

End point description

End point type

Primary

End point timeframe

From study vaccination on Day 1 up to 1 month after study vaccination

Notes
[42] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.

End point values	SSC: Group 2a: 3 prior doses of BNT162b2	SSC: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	32	30
Units: Percentage of participants
number (not applicable)	0	0

No statistical analyses for this end point

Primary: SSC: Geometric Mean Titers of SARS‑CoV‑2 Omicron (BA.4/BA.5)–Neutralizing Titers Before Vaccination and 1 Month After Vaccination

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End point title

SSC: Geometric Mean Titers of SARS‑CoV‑2 Omicron (BA.4/BA.5)–Neutralizing Titers Before Vaccination and 1 Month After Vaccination ^[44] ^[45]

End point description

GMT of SARS-CoV-2 Omicron strain–neutralizing titers before vaccination and 1 month after the study vaccination was reported in this endpoint. 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). Assay results below the LLOQ were set to 0.5*LLOQ. Evaluable immunogenicity population included all eligible randomised participants who received the study intervention to which they were randomised, had a valid and determinate immunogenicity result within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician.Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Primary

End point timeframe

before vaccination and 1 month after study vaccination

Notes
[44] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.

End point values	SSC: Group 1a: 3 prior doses of BNT162b2	SSC: Group 1b: 3 prior doses of BNT162b2	SSC: Group 2a: 3 prior doses of BNT162b2	SSC: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	11	14	30	30
Units: Titers
geometric mean (confidence interval 95%)
Pre-vaccination (n= 9, 14, 27, 28)	370.6 (62.7 to 2190.9)	225.8 (66.7 to 763.7)	199.3 (102.4 to 387.7)	312.6 (161.5 to 605.0)
1 month after vaccination (n= 11, 14, 30, 30)	3059.7 (767.0 to 12205.5)	2866.8 (772.8 to 10634.9)	3536.4 (2044.2 to 6117.9)	7155.7 (3926.9 to 13039.1)

No statistical analyses for this end point

Primary: SSC: Percentage of Participants Reporting SAEs Within 6 Months After Study Vaccination in Participants Aged >=2 to <5 Years

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End point title

SSC: Percentage of Participants Reporting SAEs Within 6 Months After Study Vaccination in Participants Aged >=2 to <5 Years ^[46] ^[47]

End point description

End point type

Primary

End point timeframe

From study vaccination on Day 1 up to 6 months after study vaccination

Notes
[46] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.

End point values	SSC: Group 2a: 3 prior doses of BNT162b2	SSC: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	32	30
Units: Percentage of participants
number (not applicable)	0	0

No statistical analyses for this end point

Primary: SSC: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers From Study Vaccination to 1 Month After Vaccination

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End point title

SSC: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers From Study Vaccination to 1 Month After Vaccination ^[48] ^[49]

End point description

GMFR of SARS-CoV-2 omicron BA.4/BA.5-neutralizing titers at 1 month after study vaccination was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ in the analysis. Evaluable immunogenicity population included all eligible randomised participants who received the study intervention to which they were randomised, had a valid and determinate immunogenicity result within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician.Participants with or without evidence of prior infection were included in the analysis.'N'=participants evaluable for this endpoint.

End point type

Primary

End point timeframe

From study vaccination on Day 1 up to 1 month after study vaccination

Notes
[48] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.

End point values	SSC: Group 1a: 3 prior doses of BNT162b2	SSC: Group 1b: 3 prior doses of BNT162b2	SSC: Group 2a: 3 prior doses of BNT162b2	SSC: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	9	14	27	28
Units: Fold rise
geometric mean (confidence interval 95%)	8.3 (2.5 to 27.3)	12.7 (6.1 to 26.3)	17.4 (11.1 to 27.4)	24.4 (14.9 to 40.0)

No statistical analyses for this end point

Primary: SSC:Percentages of Participants With Seroresponse to the Omicron (BA.4/BA.5)– Neutralizing Titers at 1 Month After Study Vaccination

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End point title

SSC:Percentages of Participants With Seroresponse to the Omicron (BA.4/BA.5)– Neutralizing Titers at 1 Month After Study Vaccination ^[50] ^[51]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement was below the lower limit of quantification (LLOQ), the postvaccination assay result of >= 4* LLOQ was considered a seroresponse. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse at 1 month after study vaccination was reported in this endpoint. Evaluable immunogenicity population included all eligible randomised participants who received the study intervention to which they were randomised, had a valid and determinate immunogenicity result within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Primary

End point timeframe

1 Month after study vaccination

Notes
[50] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[51] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.

End point values	SSC: Group 1a: 3 prior doses of BNT162b2	SSC: Group 1b: 3 prior doses of BNT162b2	SSC: Group 2a: 3 prior doses of BNT162b2	SSC: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	9	14	27	28
Units: Percentage of participants
number (confidence interval 95%)	55.6 (21.2 to 86.3)	78.6 (49.2 to 95.3)	85.2 (66.3 to 95.8)	92.9 (76.5 to 99.1)

No statistical analyses for this end point

Primary: SSC:Geometric Mean Titers of SARS‑CoV‑2 Reference-Strain-Neutralizing Titers Before Vaccination and 1 Month After Vaccination

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End point title

SSC:Geometric Mean Titers of SARS‑CoV‑2 Reference-Strain-Neutralizing Titers Before Vaccination and 1 Month After Vaccination ^[52] ^[53]

End point description

GMT of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 1 month after study vaccination was reported in this endpoint. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers & the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. Evaluable immunogenicity population included all eligible randomised participants who received the study intervention to which they were randomised, had a valid and determinate immunogenicity result within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.n=participants evaluable for specified rows.

End point type

Primary

End point timeframe

Before study vaccination and 1 Month after study vaccination

Notes
[52] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.

End point values	SSC: Group 1a: 3 prior doses of BNT162b2	SSC: Group 1b: 3 prior doses of BNT162b2	SSC: Group 2a: 3 prior doses of BNT162b2	SSC: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	11	14	30	30
Units: Titers
geometric mean (confidence interval 95%)
Before Vaccination (n=9,14,26,28)	1638.1 (690.2 to 3887.9)	1041.5 (641.3 to 1691.5)	1536.5 (952.7 to 2477.9)	2263.8 (1502.2 to 3411.5)
1 Month After Vaccination (n=11, 14, 30, 30)	7698.7 (4384.4 to 13518.6)	8443.8 (5696.8 to 12515.4)	9389.0 (6314.3 to 13961.1)	16541.7 (12265.4 to 22309.0)

No statistical analyses for this end point

Primary: SSC:GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Study Vaccination to 1 Month After Vaccination

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End point title

SSC:GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Study Vaccination to 1 Month After Vaccination ^[54] ^[55]

End point description

GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 1 month after study vaccination was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5* LLOQ in the analysis. Evaluable immunogenicity population included all eligible randomised participants who received the study intervention to which they were randomised, had a valid and determinate immunogenicity result within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Primary

End point timeframe

1 Month after study vaccination

Notes
[54] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.
[55] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.

End point values	SSC: Group 1a: 3 prior doses of BNT162b2	SSC: Group 1b: 3 prior doses of BNT162b2	SSC: Group 2a: 3 prior doses of BNT162b2	SSC: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	9	14	26	28
Units: Fold rise
geometric mean (confidence interval 95%)	5.4 (3.1 to 9.6)	8.1 (5.2 to 12.6)	5.7 (3.4 to 9.5)	7.4 (4.9 to 11.2)

No statistical analyses for this end point

Primary: SSC: Percentages of Participants With Seroresponse to the SARS-CoV-2 Reference Strain Neutralizing Titers at 1 Month After Study Vaccination

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End point title

SSC: Percentages of Participants With Seroresponse to the SARS-CoV-2 Reference Strain Neutralizing Titers at 1 Month After Study Vaccination ^[56] ^[57]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before study vaccination). If the baseline measurement was below the lower limit of quantification (LLOQ), the postvaccination assay result of >= 4 * LLOQ was considered a seroresponse. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse at 1 month after study vaccination was reported in this endpoint. Evaluable immunogenicity population included all eligible randomised participants who received the study intervention to which they were randomised, had a valid and determinate immunogenicity result within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Primary

End point timeframe

1 Month After Study Vaccination

Notes
[56] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSC; hence, only arms for SSC were included.

End point values	SSC: Group 1a: 3 prior doses of BNT162b2	SSC: Group 1b: 3 prior doses of BNT162b2	SSC: Group 2a: 3 prior doses of BNT162b2	SSC: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	9	14	26	28
Units: Percentage of participants
number (confidence interval 95%)	55.6 (21.2 to 86.3)	85.7 (57.2 to 98.2)	76.9 (56.4 to 91.0)	67.9 (47.6 to 84.1)

No statistical analyses for this end point

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

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End point title

SSD: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination ^[58] ^[59]

End point description

Local reactions recorded by participants/parents/legal guardians in electronic diary(e-diary).Redness&swelling recorded in measuring device units(mdu)converted to centimeter(cm).1 mdu=0.5 cm&graded mild:(greater than[>]0.5 to 2.0cm),moderate:>2.0 to 7.0cm,severe:>7.0 cm,Grade 4(G4): necrosis/exfoliative dermatitis(redness)&necrosis(swelling).Pain at injection site graded mild:did not interfere with daily activity,moderate:interfered with daily activity,severe: prevented daily activity&G4:emergency room[ER]visit/hospitalisation.G4 classifi ed by investigator/medically qualified person.Percentage of participants with local reactions within 7days after study vaccination and associated 2-sided 95% confidence interval(CI) based on Clopper and Pearson method.Safety population=all participants receiving at least 1dose of study intervention.Number of Participants Analysed(N)= participants evaluable.99999=data could not be generated since it was not part of specified analysis in the protocol.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination

Notes
[58] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSD; hence, only arms for SSD were included.

End point values	SSD Group 3:Participants from study C4591007 Phase 1	SSD: Group 1: 2 prior doses of BNT162b2	SSD: Group 2: 3 prior doses of BNT162b2
Number of subjects analysed	19	2	111
Units: Percentage of participants
number (confidence interval 95%)
Redness: Any	10.5 (1.3 to 33.1)	0 (-99999 to 99999)	7.2 (3.2 to 13.7)
Redness: Mild	10.5 (1.3 to 33.1)	0 (-99999 to 99999)	4.5 (1.5 to 10.2)
Redness: Moderate	0 (0.0 to 17.6)	0 (-99999 to 99999)	2.7 (0.6 to 7.7)
Redness: Severe	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Redness: Grade 4	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Swelling: Any	10.5 (1.3 to 33.1)	0 (-99999 to 99999)	4.5 (1.5 to 10.2)
Swelling: Mild	10.5 (1.3 to 33.1)	0 (-99999 to 99999)	0.9 (0.0 to 4.9)
Swelling: Moderate	0 (0.0 to 17.6)	0 (-99999 to 99999)	3.6 (1.0 to 9.0)
Swelling: Severe	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Swelling: Grade 4	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Pain at the injection site: Any	68.4 (43.4 to 87.4)	0 (-99999 to 99999)	64.0 (54.3 to 72.9)
Pain at the injection site: Mild	52.6 (28.9 to 75.6)	50.0 (-99999 to 99999)	45.0 (35.6 to 54.8)
Pain at the injection site: Moderate	15.8 (3.4 to 39.6)	0 (-99999 to 99999)	18.9 (12.1 to 27.5)
Pain at the injection site: Severe	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Pain at the injection site: Grade 4	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)

No statistical analyses for this end point

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

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End point title

SSD: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination ^[60] ^[61]

End point description

Systemic events recorded by participants/parents/legal guardians in e-diary. Fever: oral temperature >= 38.0 degree Celsius(deg C) & categorised 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,new/worsened muscle pain & new/worsened joint pain:mild:did not interfere with activity,moderate:some interference with activity & severe: prevented daily routine activity.Vomiting:mild: 1-2 times in 24hours(h),moderate:>2 times in 24h,severe:required intravenous hydration.Diarrhea:mild: 2-3 loose stools in 24h,moderate:4-5 loose stools in 24h & severe:6 or more loose stools in 24h.Except fever,G4=ER visit/hospitalisation.G4 events classified by investigator/medically qualified person. Exact 95% CI based on Clopper & Pearson method.Safety population=all participants receiving at least 1 dose of study intervention.N= participants evaluable for this endpoint.99999=data could not be generated since it was not part of specified analysis in the protocol.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination

Notes
[60] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSD; hence, only arms for SSD were included.

End point values	SSD Group 3:Participants from study C4591007 Phase 1	SSD: Group 1: 2 prior doses of BNT162b2	SSD: Group 2: 3 prior doses of BNT162b2
Number of subjects analysed	19	2	111
Units: Percentage of participants
number (confidence interval 95%)
Fever: Any	10.5 (1.3 to 33.1)	0 (-99999 to 99999)	4.5 (1.5 to 10.2)
Fever: ≥38.0 to 38.4 deg C	0 (0.0 to 17.6)	0 (-99999 to 99999)	1.8 (0.2 to 6.4)
Fever: >38.4 to 38.9 deg C	5.3 (0.1 to 26.0)	0 (-99999 to 99999)	0.9 (0.0 to 4.9)
Fever: >38.9 to 40.0 deg C	5.3 (0.1 to 26.0)	0 (-99999 to 99999)	1.8 (0.2 to 6.4)
Fever: >40.0 deg C	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Fatigue: Any	57.9 (33.5 to 79.7)	0 (-99999 to 99999)	40.5 (31.3 to 50.3)
Fatigue: Mild	36.8 (16.3 to 61.6)	0 (-99999 to 99999)	23.4 (15.9 to 32.4)
Fatigue: Moderate	15.8 (3.4 to 39.6)	0 (-99999 to 99999)	16.2 (9.9 to 24.4)
Fatigue: Severe	5.3 (0.1 to 26.0)	0 (-99999 to 99999)	0.9 (0.0 to 4.9)
Fatigue: Grade 4	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Headache: Any	36.8 (16.3 to 61.6)	0 (-99999 to 99999)	25.2 (17.5 to 34.4)
Headache: Mild	26.3 (9.1 to 51.2)	0 (-99999 to 99999)	18.0 (11.4 to 26.4)
Headache: Moderate	10.5 (1.3 to 33.1)	0 (-99999 to 99999)	6.3 (2.6 to 12.6)
Headache: Severe	0 (0.0 to 17.6)	0 (-99999 to 99999)	0.9 (0.0 to 4.9)
Headache: Grade 4	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Chills: Any	10.5 (1.3 to 33.1)	0 (-99999 to 99999)	9.0 (4.4 to 15.9)
Chills: Mild	10.5 (1.3 to 33.1)	0 (-99999 to 99999)	6.3 (2.6 to 12.6)
Chills: Moderate (n=302)	0 (0.0 to 17.6)	0 (-99999 to 99999)	2.7 (0.6 to 7.7)
Chills: Severe	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Chills: Grade 4	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Vomiting: Any	0 (0.0 to 17.6)	0 (-99999 to 99999)	3.6 (1.0 to 9.0)
Vomiting: Mild	0 (0.0 to 17.6)	0 (-99999 to 99999)	3.6 (1.0 to 9.0)
Vomiting: Moderate	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Vomiting: Severe	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Vomiting: Grade 4	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Diarrhea: Any	0 (0.0 to 17.6)	0 (-99999 to 99999)	3.6 (1.0 to 9.0)
Diarrhea: Mild	0 (0.0 to 17.6)	0 (-99999 to 99999)	3.6 (1.0 to 9.0)
Diarrhea: Moderate	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Diarrhea: Severe	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
Diarrhea: Grade 4	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
New or worsened muscle pain: Any	21.1 (6.1 to 45.6)	0 (-99999 to 99999)	13.5 (7.8 to 21.3)
New or worsened muscle pain: Mild	10.5 (1.3 to 33.1)	0 (-99999 to 99999)	7.2 (3.2 to 13.7)
New or worsened muscle pain: Moderate	10.5 (1.3 to 33.1)	0 (-99999 to 99999)	6.3 (2.6 to 12.6)
New or worsened muscle pain: Severe	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
New or worsened muscle pain: Grade 4	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
New or worsened joint pain: Any	10.5 (1.3 to 33.1)	0 (-99999 to 99999)	9.0 (4.4 to 15.9)
New or worsened joint pain: Mild	5.3 (0.1 to 26.0)	0 (-99999 to 99999)	7.2 (3.2 to 13.7)
New or worsened joint pain: Moderate	5.3 (0.1 to 26.0)	0 (-99999 to 99999)	1.8 (0.2 to 6.4)
New or worsened joint pain: Severe	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)
New or worsened joint pain: Grade 4	0 (0.0 to 17.6)	0 (-99999 to 99999)	0 (0.0 to 3.3)

No statistical analyses for this end point

Primary: SSD: Percentage of Participants Reporting Adverse Events (AEs) 1 Month After Study Vaccination

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End point title

SSD: Percentage of Participants Reporting Adverse Events (AEs) 1 Month After Study Vaccination ^[62] ^[63]

End point description

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 endpoint. 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 endpoint. Safety population included all participants who received at least 1 dose of the study intervention. 99999= data could not be generated since it was not part of specified analysis in the protocol.

End point type

Primary

End point timeframe

From study vaccination on Day 1 up to 1 month after study vaccination

Notes
[62] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[63] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSD; hence, only arms for SSD were included.

End point values	SSD Group 3:Participants from study C4591007 Phase 1	SSD: Group 1: 2 prior doses of BNT162b2	SSD: Group 2: 3 prior doses of BNT162b2
Number of subjects analysed	19	2	113
Units: Percentage of participants
number (confidence interval 95%)	15.8 (3.4 to 39.6)	0.0 (-99999 to 99999)	3.5 (1.0 to 8.8)

No statistical analyses for this end point

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

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End point title

SSD: Percentage of Participants Reporting Serious Adverse Events (SAEs) Within 6 Months After Study Vaccination ^[64] ^[65]

End point description

An SAE was defi ned 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 hospitalisation or prolongation of existing hospitalisation. Safety population included all participants who received at least 1 dose of the study intervention.

End point type

Primary

End point timeframe

From study vaccination on Day 1 up to 6 months after study vaccination

Notes
[64] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[65] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSD; hence, only arms for SSD were included.

End point values	SSD Group 3:Participants from study C4591007 Phase 1	SSD: Group 1: 2 prior doses of BNT162b2	SSD: Group 2: 3 prior doses of BNT162b2
Number of subjects analysed	19	2	113
Units: Percentage of participants
number (not applicable)	0	0	0

No statistical analyses for this end point

Primary: SSD: Percentages of Participants With Seroresponse to the Omicron (BA.4/BA.5)– Neutralizing Titers at 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3)

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End point title

SSD: Percentages of Participants With Seroresponse to the Omicron (BA.4/BA.5)– Neutralizing Titers at 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3) ^[66]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before Dose 4 for C4591048 Substudy D Group 2 and before Dose 3 for C4591007). If the baseline measurement was below the lower limit of quantifi cation (LLOQ), the postvaccination assay result of >= 4 × LLOQ was considered a seroresponse. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Percentage of participants achieving seroresponse at 1 month after study vaccination was reported in this endpoint. Evaluable immunogenicity population was analyzed. Results include those from a comparator group of C4591007 (NCT04816643) Phase 2/3 participants of the same age who received 3 doses of original BNT162b2 10 μg as of the data cutoff date of 27 May 2022.Participants with or without evidence of prior infection were included in the analysis.'N'=participants evaluable for this endpoint.

End point type

Primary

End point timeframe

1 month after Dose 4 for Group 2 and 1 month after Dose 3 for C4591007 control arm

Notes
[66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSD; hence, only arms for SSD were included.

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 mcg
Number of subjects analysed	101	112
Units: Percentage of participants
number (confidence interval 95%)	53.5 (43.3 to 63.5)	52.7 (43.0 to 62.2)

Group 2 and Historical cohort from C4591007

Statistical analysis description

Adjusted diff erence in proportions based on the Miettinen and Nurminen method stratifi ed by baseline neutralizing titer category (< median, ≥ median), expressed as a percentage (bivalent BNT162b2 [original/Omi BA.4/BA.5] 10 μg - BNT162b2 10 μg). 2-Sided CI, based on the Miettinen and Nurminen method for the diff erence in proportions stratifi ed by baseline neutralizing titer category (< median,>= median), expressed as a percentage.

Comparison groups

SSD: Group 2: 3 prior doses of BNT162b2 v SSD Historical cohort: C4591007 BNT162b2 10 mcg

Number of subjects included in analysis

213

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Percentage Difference

Point estimate

8.76

Confidence interval

level

95%

sides

2-sided

lower limit

-2.47

upper limit

19.99

Primary: SSD:Geometric Mean Ratio(GMR)Based on Geometric Mean Titers of Severe Acute Respiratory Syndrome Coronavirus 2(SARS‑CoV‑2)Omicron(BA.4/BA.5)-Neutralizing Titers at 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants(1 Month After Dose 3)

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End point title

SSD:Geometric Mean Ratio(GMR)Based on Geometric Mean Titers of Severe Acute Respiratory Syndrome Coronavirus 2(SARS‑CoV‑2)Omicron(BA.4/BA.5)-Neutralizing Titers at 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants(1 Month After Dose 3) ^[67]

End point description

GMTs and the corresponding 2-sided CIs were calculated by exponentiating the least square means and the corresponding CIs based on analysis of log-transformed assay results using a linear regression model with baseline log-transformed neutralizing titers, postbaseline infection status, and vaccine group as covariates. Evaluable immunogenicity population included all eligible randomised participants who received the study intervention to which they were randomised, had a valid and determinate immunogenicity result within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Results include those from a comparator group of C4591007 (NCT04816643) Phase 2/3 participants of the same age who received 3 doses of original BNT162b2 10 μg as of the data cutoff date of 27 May 2022.Participants with or without evidence of prior infection were included in the analysis.'N'=participants evaluable for this endpoint.

End point type

Primary

End point timeframe

1 month after Dose 4 for Group 2 and 1 month after Dose 3 for C4591007 control arm

Notes
[67] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSD; hence, only arms for SSD were included.

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 mcg
Number of subjects analysed	101	112
Units: Titers
geometric mean (confidence interval 95%)	1836.1 (1593.8 to 2115.2)	1632.5 (1427.5 to 1867.0)

Group 2 and Historical cohort from C4591007

Statistical analysis description

GMRs and 2-sided CIs were calculated by exponentiating the difference of LSMeans for the assay and the corresponding CIs based on a linear regression model with baseline log-transformed neutralizing titers, postbaseline infection status, and vaccine group as covariates.

Comparison groups

SSD: Group 2: 3 prior doses of BNT162b2 v SSD Historical cohort: C4591007 BNT162b2 10 mcg

Number of subjects included in analysis

213

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric Mean Ratio

Point estimate

1.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

1.37

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

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End point title

SSE: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination ^[68] ^[69]

End point description

Local reactions were recorded by participants or their parents/legal guardians in an e-diary. Redness and swelling were measured and recorded in mdu where, 1 mdu =0.5 cm and were graded as mild (>=0.5 to 2.0 cm), moderate (>2.0 to 7.0 cm), severe (>7.0 cm) and Grade 4 (necrosis [redness and swelling] or exfoliative dermatitis [redness]). Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity & Grade 4: ER visit/hospitalization. Grade 4 reactions were classified by investigator/medically qualified person. Safety population consisted of all participants who had received at least 1 dose of the study intervention. Here, "Number of Participants Analyzed (N)" signifies number of participants evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination

Notes
[68] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSE; hence, only arms for SSE were included.

End point values	SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg
Number of subjects analysed	302
Units: Percentage of Participants
number (confidence interval 95%)
Redness: Any	6.0 (3.6 to 9.3)
Redness: Mild	4.6 (2.6 to 7.7)
Redness: Moderate	1.3 (0.4 to 3.4)
Redness: Severe	0 (0.0 to 1.2)
Redness: Grade 4	0 (0.0 to 1.2)
Swelling: Any	9.3 (6.2 to 13.1)
Swelling: Mild	6.0 (3.6 to 9.3)
Swelling: Moderate	3.0 (1.4 to 5.6)
Swelling: Severe	0.3 (0.0 to 1.8)
Swelling: Grade 4	0 (0.0 to 1.2)
Pain at the injection site: Any	42.7 (37.1 to 48.5)
Pain at the injection site: Mild	31.5 (26.3 to 37.0)
Pain at the injection site: Moderate	11.3 (7.9 to 15.4)
Pain at the injection site: Severe	0 (0.0 to 1.2)
Pain at the injection site: Grade 4	0 (0.0 to 1.2)

No statistical analyses for this end point

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

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End point title

SSE: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination ^[70] ^[71]

End point description

Systemic events were recorded by participants or their parents/legal guardians in e-diary. Fever was defined as 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 & >40.0 deg C. Fatigue, headache, chills ,new/worsened muscle pain & new/worsened joint pain were graded as mild: did not interfere with activity, moderate: some interference with activity & severe: prevented daily routine activity. Vomiting was graded as mild: 1-2 times in 24h, moderate:>2 times in 24h, severe:required intravenous hydration. Diarrhea was graded as mild:2-3 loose stools in 24h, moderate:4-5 loose stools in 24h & severe:6 or more loose stools in 24h.For all systemic events except fever, G4=ER visit/hospitalization & were classified by investigator/medically qualified person. Safety population consisted of all participants who had received at least 1 dose of study intervention. "N"=participants evaluable and "n"=participants evaluable for each specified rows.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination

Notes
[70] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSE; hence, only arms for SSE were included.

End point values	SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg
Number of subjects analysed	302
Units: Percentage of Participants
number (confidence interval 95%)
Fever: Any (n=301)	4.7 (2.6 to 7.7)
Fever: >=38.0 to 38.4 deg C (n=301)	2.0 (0.7 to 4.3)
Fever: >38.4 to 38.9 deg C (n=301)	1.7 (0.5 to 3.8)
Fever: >38.9 to 40.0 deg C (n=301)	0.3 (0.0 to 1.8)
Fever: >40.0 deg C (n=301)	0.3 (0.0 to 1.8)
Fever: Unknown (n=301)	0.3 (0.0 to 1.8)
Fatigue: Any (n=302)	14.9 (11.1 to 19.4)
Fatigue: Mild (n=302)	7.6 (4.9 to 11.2)
Fatigue: Moderate (n=302)	6.6 (4.1 to 10.0)
Fatigue: Severe (n=302)	0.7 (0.1 to 2.4)
Fatigue: Grade 4 (n=302)	0 (0.0 to 1.2)
Headache: Any (n=302)	14.2 (10.5 to 18.7)
Headache: Mild (n=302)	7.9 (5.2 to 11.6)
Headache: Moderate (n=302)	6.0 (3.6 to 9.3)
Headache: Severe (n=302)	0.3 (0.0 to 1.8)
Headache: Grade 4 (n=302)	0 (0.0 to 1.2)
Chills: Any (n=302)	5.6 (3.3 to 8.9)
Chills: Mild (n=302)	3.6 (1.8 to 6.4)
Chills: Moderate (n=302)	2.0 (0.7 to 4.3)
Chills: Severe (n=302)	0 (0.0 to 1.2)
Chills: Grade 4 (n=302)	0 (0.0 to 1.2)
Vomiting: Any (n=302)	4.3 (2.3 to 7.2)
Vomiting: Mild (n=302)	3.3 (1.6 to 6.0)
Vomiting: Moderate (n=302)	1.0 (0.2 to 2.9)
Vomiting: Severe (n=302)	0 (0.0 to 1.2)
Vomiting: Grade 4 (n=302)	0 (0.0 to 1.2)
Diarrhea: Any (n=302)	7.3 (4.6 to 10.8)
Diarrhea: Mild (n=302)	6.0 (3.6 to 9.3)
Diarrhea: Moderate (n=302)	1.3 (0.4 to 3.4)
Diarrhea: Severe (n=302)	0 (0.0 to 1.2)
Diarrhea: Grade 4 (n=302)	0 (0.0 to 1.2)
New or worsened muscle pain: Any (n=302)	10.3 (7.1 to 14.3)
New or worsened muscle pain: Mild (n=302)	4.6 (2.6 to 7.7)
New or worsened muscle pain: Moderate (n=302)	5.6 (3.3 to 8.9)
New or worsened muscle pain: Severe (n=302)	0 (0.0 to 1.2)
New or worsened muscle pain: Grade 4 (n=302)	0 (0 to 1.2)
New or worsened joint pain: Any (n=302)	4.6 (2.6 to 7.7)
New or worsened joint pain: Mild (n=302)	2.0 (0.7 to 4.3)
New or worsened joint pain: Moderate (n=302)	2.6 (1.2 to 5.2)
New or worsened joint pain: Severe (n=302)	0 (0.0 to 1.2)
New or worsened joint pain: Grade 4 (n=302)	0 (0.0 to 1.2)

No statistical analyses for this end point

Primary: SSE: Percentage of Participants Reporting AEs 1 Month After Study Vaccination

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End point title

SSE: Percentage of Participants Reporting AEs 1 Month After Study Vaccination ^[72] ^[73]

End point description

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study vaccination, whether or not considered related to the study vaccination. Percentage of participants reporting AEs within 1 month after study vaccination were reported in this endpoint. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this endpoint. Safety population consisted of all participants who had received at least 1 dose of the study intervention.

End point type

Primary

End point timeframe

Within 1 Month after study vaccination

Notes
[72] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSE; hence, only arms for SSE were included.

End point values	SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg
Number of subjects analysed	310
Units: Percentage of Participants
number (confidence interval 95%)	3.5 (1.8 to 6.3)

No statistical analyses for this end point

Primary: SSE: Percentage of Participants Reporting SAEs Within 6 Months After Study Vaccination

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End point title

SSE: Percentage of Participants Reporting SAEs Within 6 Months After Study Vaccination ^[74] ^[75]

End point description

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. Safety population consisted of all participants who have received at least 1 dose of the study intervention.

End point type

Primary

End point timeframe

Within 6 months after study vaccination

Notes
[74] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive analysis was planned for this endpoint.
[75] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSE; hence, only arms for SSE were included.

End point values	SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg
Number of subjects analysed	310
Units: Percentage of participants
number (confidence interval 95%)	1.0 (0.2 to 2.8)

No statistical analyses for this end point

Primary: SSE: GMR Based on GMT of SARS-CoV-2 Omicron XBB.1.5–Neutralizing Titers at 1 Month After Vaccination Compared With C4591054 – Substudy A Vaccine-Experienced Participants >=12 Years of Age

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End point title

SSE: GMR Based on GMT of SARS-CoV-2 Omicron XBB.1.5–Neutralizing Titers at 1 Month After Vaccination Compared With C4591054 – Substudy A Vaccine-Experienced Participants >=12 Years of Age ^[76]

End point description

GMT is presented in descriptive section & GMR is presented in statistical analysis section. GMTs & corresponding 2-sided 95% CIs were calculated by exponentiating LS means & corresponding CIs based on analysis of log-transformed assay results using linear regression model with baseline log-transformed neutralizing titers, postbaseline infection status & vaccine group as covariates. Evaluable immunogenicity population: All eligible participants who received study intervention to which they were assigned, had at least 1 valid and determinate immunogenicity results from the blood sample collected within 28 to 42 days after study vaccination, had no other important protocol deviations as determined by clinician. =participants evaluable for this endpoint.

End point type

Primary

End point timeframe

1 Month after vaccination

Notes
[76] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSE; hence, only arms for SSE were included.

End point values	SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg	SSE Historical Cohort: C4591054 BNT162b2 (Omi XBB.1.5) 30mcg
Number of subjects analysed	285	300
Units: Titer
geometric mean (confidence interval 95%)	6569.3 (5781.6 to 7464.3)	3635.9 (3210.5 to 4117.6)

Geometric Mean Ratio

Statistical analysis description

GMRs and 2-sided CIs were calculated by exponentiating the difference of LS Mean for the assay and the corresponding CIs based on analysis of log-transformed assay results using a linear regression model with baseline log-transformed neutralizing titers, postbaseline infection status and vaccine group as covariates.

Comparison groups

SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg v SSE Historical Cohort: C4591054 BNT162b2 (Omi XBB.1.5) 30mcg

Number of subjects included in analysis

585

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[77]

Method

Parameter type

Geometric Mean Ratio

Point estimate

1.81

Confidence interval

level

95%

sides

2-sided

lower limit

1.51

upper limit

2.16

Notes
[77] - Immunobridging success based on the GMR will be declared if the lower limit of the 2-sided 95% CI for the GMR is greater than 0.67 (1.5-fold criterion) and the point estimate of the GMR is >=0.8.

Primary: SSE: Percentage of Participants and Difference in Percentage of Participants With Seroresponse to Omicron XBB.1.5 at 1 Month After Study Vaccination Compared With C4591054 – Substudy A Vaccine-Experienced Participants >=12 Years of Age

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End point title

SSE: Percentage of Participants and Difference in Percentage of Participants With Seroresponse to Omicron XBB.1.5 at 1 Month After Study Vaccination Compared With C4591054 – Substudy A Vaccine-Experienced Participants >=12 Years of Age ^[78]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (1 month after study vaccination for C4591048 SSE and 1 month after vaccination for C4591054). If the baseline measurement was below LLOQ, postvaccination assay result of >= 4*LLOQ was considered a seroresponse. Exact 2-sided 95% CI was based on Clopper and Pearson method. Percentage of participants with seroresponse were presented in descriptive analysis and difference in percentage of participants with seroresponse were presented in statistical analysis section. Evaluable immunogenicity population: All eligible participants with 1 dose of study vaccination to which they were assigned, had at least 1 valid & determinate immunogenicity result from blood sample collected within 28-42 days after study vaccination, had no other important protocol deviations as determined by clinician. 'N'=number of participants evaluable for this endpoint.

End point type

Primary

End point timeframe

1 Month after vaccination

Notes
[78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSE; hence, only arms for SSE were included.

End point values	SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg	SSE Historical Cohort: C4591054 BNT162b2 (Omi XBB.1.5) 30mcg
Number of subjects analysed	285	300
Units: Percentage of Participants
number (confidence interval 95%)	88.8 (84.5 to 92.2)	77.0 (71.8 to 81.6)

Percentage of participants with seroresponse

Statistical analysis description

Adjusted difference in percentage based on the Miettinen and Nurminen method stratified by baseline neutralizing titer category (<median, >=median), expressed as a percentage (C4591048 >=5 to <12 Years - C4591054 >=12 Years)).

Comparison groups

SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg v SSE Historical Cohort: C4591054 BNT162b2 (Omi XBB.1.5) 30mcg

Number of subjects included in analysis

585

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[79]

Method

Parameter type

Difference in percentage

Point estimate

8.97

Confidence interval

level

95%

sides

2-sided

lower limit

3.91

upper limit

14.02

Notes
[79] - Immunobridging success based on seroresponse rate difference will be declared if the lower limit of the 2-sided 95% CI for the difference in percentages of participants with seroresponse is greater than -10%.

Secondary: SSB: GMR Based on Geometric Mean Titers of SARS‑CoV‑2 Reference-Strain-Neutralizing Titers at 1 Month After Dose 4 for Group 2 and at 1 Month After Dose 3 for C4591007 Phase 2/3 Participants

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End point title

SSB: GMR Based on Geometric Mean Titers of SARS‑CoV‑2 Reference-Strain-Neutralizing Titers at 1 Month After Dose 4 for Group 2 and at 1 Month After Dose 3 for C4591007 Phase 2/3 Participants ^[80]

End point description

GMTs and the corresponding 2-sided CIs were calculated by exponentiating the least square means & the corresponding CIs based on analysis of log-transformed assay results using linear regression model with baseline log-transformed neutralizing titers,postbaseline infection status&vaccine group as covariates.Assay results below the LLOQ were set to 0.5*LLOQ.Evaluable immunogenicity population included all eligible participants who received the study intervention to which they were assigned,had atleast one valid&determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination,and had no other important protocol deviations as determined by the clinician.Results are presented for per-protocol subset which included a random sample of 240 participants selected from the full group and comprised the same percentages of participants in each age group & baseline SARS-CoV-2 infection status group as full group.'N'=participants evaluable.

End point type

Secondary

End point timeframe

1 month after Dose 4 for Group 2 and 1 month after Dose 3 for C4591007 control arm

Notes
[80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2	SSB Historical cohort:C4591007 BNT162b2 >=6 months to<2 years	SSB Historical cohort: C4591007 BNT162b2 3 mcg
Number of subjects analysed	62	161	72	166
Units: Titers
geometric mean (confidence interval 95%)	5965.4 (4958.5 to 7176.8)	6921.5 (6160.2 to 7777.0)	7108.9 (5989.2 to 8438.0)	7384.8 (6584.6 to 8282.3)

Geometric Mean Ratio

Statistical analysis description

GMRs and 2-sided CIs were calculated by exponentiating the difference of LSMeans for the assay and the corresponding CIs based on analysis of log-transformed assay results using a linear regression model with baseline log-transformed neutralizing titers, postbaseline infection status, age group and vaccine group as covariates.

Comparison groups

SSB: Group 2b: 3 prior doses of BNT162b2 v SSB Historical cohort: C4591007 BNT162b2 3 mcg

Number of subjects included in analysis

327

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

Geometric Mean Ratio

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.11

Geometric Mean Ratio

Statistical analysis description

GMRs and 2-sided CIs were calculated by exponentiating the difference of LSMeans for the assay and the corresponding CIs based on analysis of log-transformed assay results using a linear regression model with baseline log-transformed neutralizing titers, postbaseline infection status, age group and vaccine group as covariates.

Comparison groups

SSB: Group 2a: 3 prior doses of BNT162b2 v SSB Historical cohort:C4591007 BNT162b2 >=6 months to<2 years

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

Geometric Mean Ratio

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

1.08

Secondary: SSB: Percentage of Participants With Seroresponse to the SARS‑CoV‑2 Reference-Strain-Neutralizing Titers at 1 Month After Dose 4 for Group 2 and at 1 Month After Dose 3 for C4591007 Phase 2/3 Participants

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End point title

SSB: Percentage of Participants With Seroresponse to the SARS‑CoV‑2 Reference-Strain-Neutralizing Titers at 1 Month After Dose 4 for Group 2 and at 1 Month After Dose 3 for C4591007 Phase 2/3 Participants ^[81]

End point description

Seroresponse was defined as achieving>= 4-fold rise from baseline(before Dose 4 for C4591048 Substudy B Group 2 and before Dose 3 for C4591007).If the baseline measurement was below LLOQ,the postvaccination assay result of>= 4*LLOQ was considered a seroresponse.Exact 2-sided 95% CI was based on Clopper and Pearson method.Evaluable immunogenicity population included all eligible participants who received the study intervention to which they were assigned,had atleast one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination,and had no other important protocol deviations as determined by the clinician.Results were presented for per-protocol subset which included a random sample of 240 participants selected from the full group and comprised of the same percentage of participants in each age group and baseline SARS-CoV-2 infection status group as the full group.'N'=participants evaluable.

End point type

Secondary

End point timeframe

1 month after Dose 4 for Group 2 and 1 month after Dose 3 for C4591007 control arm

Notes
[81] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2	SSB Historical cohort:C4591007 BNT162b2 >=6 months to<2 years	SSB Historical cohort: C4591007 BNT162b2 3 mcg
Number of subjects analysed	62	161	72	166
Units: Percentage of participants
number (confidence interval 95%)	40.3 (28.1 to 53.6)	52.8 (44.8 to 60.7)	44.4 (32.7 to 56.6)	65.7 (57.9 to 72.8)

Percentages of Participants With Seroresponse

Statistical analysis description

Comparison groups

SSB: Group 2a: 3 prior doses of BNT162b2 v SSB Historical cohort:C4591007 BNT162b2 >=6 months to<2 years

Number of subjects included in analysis

134

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[82]

Method

Parameter type

Percentage Difference

Point estimate

5.67

Confidence interval

level

95%

sides

2-sided

lower limit

-7.43

upper limit

18.77

Notes
[82] - Noninferiority was established if the lower bound of the 2-sided 95% CI for the difference in percentage was greater than -10%.

Secondary: SSB: GMT of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at Dose 4 and 1 Month After Dose 4

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End point title

SSB: GMT of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at Dose 4 and 1 Month After Dose 4 ^[83]

End point description

GMT of SARS-CoV-2 Omicron strain–neutralizing titers at 1 month after the study vaccination was reported in this endpoint. 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). Assay results below the LLOQ were set to 0.5 *LLOQ. Evaluable immunogenicity population included all eligible participants who received the study intervention to which they were assigned, had atleast one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Participants with or without evidence of prior infection were included in the analysis.'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

Group 2: At Dose 4 and 1 month after Dose 4

Notes
[83] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	78	196
Units: Titers
geometric mean (confidence interval 95%)
At dose 4 (n=74, 192)	293.9 (195.4 to 441.9)	224.1 (177.2 to 283.5)
1 month after Dose 4 (n=78, 196)	1905.1 (1328.9 to 2731.2)	2384.9 (1965.4 to 2893.9)

No statistical analyses for this end point

Secondary: SSB: GMT of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at Dose 3 and 1 Month After Dose 3: Group 1 Only

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End point title

SSB: GMT of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at Dose 3 and 1 Month After Dose 3: Group 1 Only ^[84]

End point description

GMT of SARS-CoV-2 omicron BA.4/BA.5-neutralizing titers at dose 3 and 1 month after dose 3 was reported in this endpoint. 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). Assay results below the LLOQ were set to 0.5 *LLOQ. Evaluable immunogenicity population (third dose) included all eligible participants who received first study intervention as third dose to which they were assigned, had at least one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the third dose, and had no other important protocol deviations as determined by the clinician. Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint. ‘n’= Participants evaluable for specified rows.

End point type

Secondary

End point timeframe

At dose 3 and 1 month after dose 3

Notes
[84] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	14	10
Units: Titer
geometric mean (confidence interval 95%)
Dose 3 (n= 14, 10)	142.5 (45.6 to 444.9)	323.2 (83.7 to 1248.8)
1 month after dose 3 (n=13, 10)	1548.9 (408.0 to 5879.6)	2699.9 (580.8 to 12551.1)

No statistical analyses for this end point

Secondary: SSB: GMT of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at 1 Month After Dose 4: Group 1 Only

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End point title

SSB: GMT of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at 1 Month After Dose 4: Group 1 Only ^[85]

End point description

GMT of SARS-CoV-2 Omicron BA.4/BA.5–neutralizing titers at 1 month after dose 4 was reported in this endpoint. 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). Assay results below the LLOQ were set to 0.5 *LLOQ. Evaluable immunogenicity population (fourth dose) included all eligible participants who received 2 doses of the study intervention as third and fourth dose to which they were assigned, had at least one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

At 1 month after dose 4

Notes
[85] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	16	9
Units: Titer
geometric mean (confidence interval 95%)	2800.0 (1260.5 to 6219.8)	4128.5 (1158.9 to 14708.1)

No statistical analyses for this end point

Secondary: SSB: GMT of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Dose 4 and 1 Month After Dose 4

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End point title

SSB: GMT of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Dose 4 and 1 Month After Dose 4 ^[86]

End point description

GMT of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 1 month after study vaccination was reported in this endpoint.GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers & the corresponding CIs(based on Student's t distribution).Assay results below the LLOQ were set to 0.5* LLOQ.Evaluable immunogenicity population included all eligible participants who received the study intervention to which they were assigned, had atleast one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

Baseline (at dose 4) and 1 Month after Dose 4

Notes
[86] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	78	196
Units: Titers
geometric mean (confidence interval 99%)
Pre-vaccination (n=74, 192)	1688.3 (1271.6 to 2241.6)	1734.9 (1466.0 to 2053.3)
1 month after Dose 4 (n= 78,196)	6312.0 (5143.6 to 7746.0)	7897.3 (6952.0 to 8971.2)

No statistical analyses for this end point

Secondary: SSB: GMT of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Dose 3 and 1 Month After Dose 3: Group 1 Only

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End point title

SSB: GMT of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Dose 3 and 1 Month After Dose 3: Group 1 Only ^[87]

End point description

GMT of SARS-CoV-2 reference strain–neutralizing titers at dose 3 and 1 month after dose 3 was reported in this endpoint. 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). Assay results below the LLOQ were set to 0.5 *LLOQ. Evaluable immunogenicity population (third dose) included all eligible participants who received first study intervention as third dose to which they were assigned, had at least one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the third dose, and had no other important protocol deviations as determined by the clinician.Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint. ‘n’= Participants evaluable for specified rows.

End point type

Secondary

End point timeframe

At dose 3 and 1 month After dose 3

Notes
[87] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	14	10
Units: Titer
geometric mean (confidence interval 95%)
Dose 3 (n= 14, 10)	271.7 (114.6 to 644.3)	636.6 (262.7 to 1542.5)
1 month after dose 3 (n= 13, 10)	3536.4 (2024.4 to 6177.6)	2576.5 (1204.5 to 5511.5)

No statistical analyses for this end point

Secondary: SSB: GMT of SARS-CoV-2 Reference-Strain–Neutralizing Titers at 1 Month After Dose 4: Group 1 Only

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End point title

SSB: GMT of SARS-CoV-2 Reference-Strain–Neutralizing Titers at 1 Month After Dose 4: Group 1 Only ^[88]

End point description

GMT of SARS-CoV-2 reference strain–neutralizing titers at 1 month after dose 4 was reported in this endpoint. 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). Assay results below the LLOQ were set to 0.5 *LLOQ. Evaluable immunogenicity population (fourth dose) included all eligible participants who received 2 doses of the study intervention as third and fourth dose to which they were assigned, had at least one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

At 1 month after dose 4

Notes
[88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	16	9
Units: Titer
geometric mean (confidence interval 95%)	2357.1 (1485.0 to 3741.3)	2468.2 (1188.8 to 5124.6)

No statistical analyses for this end point

Secondary: SSB: GMFR of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers From Dose 3 to 1 Month After Dose 3: Group 1 Only

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End point title

SSB: GMFR of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers From Dose 3 to 1 Month After Dose 3: Group 1 Only ^[89]

End point description

GMFR of SARS-CoV-2 omicron BA.4/BA.5-neutralizing titers from dose 3 to 1 month after dose 3 was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ in the analysis. Evaluable immunogenicity population (third dose) included all eligible participants who received first study intervention as third dose to which they were assigned, had at least one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the third dose, and had no other important protocol deviations as determined by the clinician.Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

From dose 3 to 1 month after dose 3

Notes
[89] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	11	10
Units: Fold rise
geometric mean (confidence interval 95%)	9.1 (3.6 to 22.8)	8.4 (3.8 to 18.1)

No statistical analyses for this end point

Secondary: SSB: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers From Dose 4 to 1 Month after Dose 4

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End point title

SSB: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers From Dose 4 to 1 Month after Dose 4 ^[90]

End point description

GMFR of SARS-CoV-2 omicron BA.4/BA.5-neutralizing titers from dose 4 to 1 month after dose 4 was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ in the analysis. Evaluable immunogenicity population included all eligible participants who received the study intervention to which they were assigned, had atleast one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

From dose 4 to 1 month after dose 4

Notes
[90] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	74	192
Units: Fold rise
geometric mean (confidence interval 95%)	6.7 (5.1 to 8.8)	10.5 (8.9 to 12.5)

No statistical analyses for this end point

Secondary: SSB: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Dose 3 to 1 Month After Dose 3: Group 1 Only

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End point title

SSB: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Dose 3 to 1 Month After Dose 3: Group 1 Only ^[91]

End point description

GMFR of SARS-CoV-2 reference strain-neutralizing titers from dose 3 to 1 month after dose 3 was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ in the analysis. Evaluable immunogenicity population (third dose) included all eligible participants who received first study intervention as third dose to which they were assigned, had at least one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the third dose, and had no other important protocol deviations as determined by the clinician.Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

From dose 3 to 1 month after dose 3

Notes
[91] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	11	10
Units: Fold rise
geometric mean (confidence interval 95%)	12.6 (4.9 to 32.1)	4.0 (2.2 to 7.5)

No statistical analyses for this end point

Secondary: SSB: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Dose 4 to 1 Month after Dose 4

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End point title

SSB: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Dose 4 to 1 Month after Dose 4 ^[92]

End point description

GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination from dose 4 to 1 month after dose 4 was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 *LLOQ in the analysis. Evaluable immunogenicity population included all eligible participants who received the study intervention to which they were assigned, had atleast one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

From dose 4 to 1 month after dose 4

Notes
[92] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	74	192
Units: Fold rise
geometric mean (confidence interval 95%)	3.7 (2.9 to 4.7)	4.5 (3.9 to 5.2)

No statistical analyses for this end point

Secondary: SSB: GMFR of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers From Dose 3 to 1 Month After Dose 4: Group 1 Only

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End point title

SSB: GMFR of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers From Dose 3 to 1 Month After Dose 4: Group 1 Only ^[93]

End point description

GMFR of SARS-CoV-2 omicron BA.4/BA.5-neutralizing titers at dose 3 to 1 month After dose 4 was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ in the analysis. Evaluable immunogenicity population (fourth dose) included all eligible participants who received 2 doses of the study intervention as third and fourth dose to which they were assigned, had at least one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

From dose 3 to 1 month after dose 4

Notes
[93] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	14	9
Units: Fold rise
geometric mean (confidence interval 95%)	14.9 (7.4 to 30.0)	17.2 (7.6 to 39.0)

No statistical analyses for this end point

Secondary: SSB: Percentage of Participants With Seroresponse to Reference-Strain-Neutralizing Titers at 1 Month After Dose 4

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End point title

SSB: Percentage of Participants With Seroresponse to Reference-Strain-Neutralizing Titers at 1 Month After Dose 4 ^[94]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before Dose 4 for C4591048 Substudy B Group 2). If the baseline measurement was below the lower limit of quantification (LLOQ), the postvaccination assay result of >= 4* LLOQ was considered a seroresponse. Evaluable immunogenicity population included all eligible participants who received the study intervention to which they were assigned, had atleast one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician.Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse to reference-strain-neutralizing titers at 1 month after dose 4 was reported in this endpoint. Participants with or without evidence of prior infection were included in the analysis.'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

1 Month after Dose 4

Notes
[94] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	74	192
Units: Percentage of participants
number (confidence interval 95%)	43.2 (31.8 to 55.3)	52.1 (44.8 to 59.3)

No statistical analyses for this end point

Secondary: SSB: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers At 1 Month After Dose 4: Group 1 Only

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End point title

SSB: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers At 1 Month After Dose 4: Group 1 Only ^[95]

End point description

GMFR of SARS-CoV-2 reference strain-neutralizing titers at 1 month after dose 4 was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ in the analysis. Evaluable immunogenicity population included all eligible participants who received 2 doses of the study intervention as third and fourth dose to which they were assigned, had at least one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Participants with or without evidence of prior infection were included in the analysis. N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

At 1 month after dose 4

Notes
[95] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	14	9
Units: Fold rise
geometric mean (confidence interval 95%)	8.8 (4.5 to 17.0)	4.6 (2.4 to 8.8)

No statistical analyses for this end point

Secondary: SSB: Percentage of Participants With Seroresponse to Reference-Strain-Neutralizing Titers at 1 Month After Dose 3: Group 1 Only

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End point title

SSB: Percentage of Participants With Seroresponse to Reference-Strain-Neutralizing Titers at 1 Month After Dose 3: Group 1 Only ^[96]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before Dose 3). If the baseline measurement was below the LLOQ, the postvaccination assay result of >= 4*LLOQ was considered a seroresponse.Evaluable immunogenicity population (third dose) included all eligible participants who received first study intervention as third dose to which they were assigned, had at least one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the third dose, and had no other important protocol deviations as determined by the clinician. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse to reference-strain-neutralizing titers at 1 month after dose 3 was reported in this endpoint.

End point type

Secondary

End point timeframe

1 month after dose 3

Notes
[96] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	11	10
Units: Percentage of participants
number (confidence interval 95%)	81.8 (48.2 to 97.7)	50.0 (18.7 to 81.3)

No statistical analyses for this end point

Secondary: SSB: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at 1 Month After Dose 4

Top of page

End point title

SSB: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at 1 Month After Dose 4 ^[97]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before Dose 4 for C4591048 Substudy D Group 2). If the baseline measurement was below the lower limit of quantification (LLOQ), the postvaccination assay result of >= 4* LLOQ was considered a seroresponse. Evaluable immunogenicity population included all eligible participants who received the study intervention to which they were assigned, had atleast one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse to SARS-CoV-2 omicron BA.4/BA.5–neutralizing titers at 1 month after dose 4 was reported in this endpoint. Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

1 Month after Dose 4

Notes
[97] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2
Number of subjects analysed	74	192
Units: Percentage of participants
number (confidence interval 95%)	56.8 (44.7 to 68.2)	74.5 (67.7 to 80.5)

No statistical analyses for this end point

Secondary: SSB: Percentage of Participants With Seroresponse to Reference-Strain-Neutralizing Titers at 1 Month After Dose 4: Group 1 Only

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End point title

SSB: Percentage of Participants With Seroresponse to Reference-Strain-Neutralizing Titers at 1 Month After Dose 4: Group 1 Only ^[98]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before Dose 3). If the baseline measurement was below the LLOQ, the postvaccination assay result of >= 4*LLOQ was considered a seroresponse. Evaluable immunogenicity population (fourth dose) included all eligible participants who received 2 doses of the study intervention as third and fourth dose to which they were assigned, had at least one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse to reference-strain-neutralizing titers at 1 month after dose 4 was reported in this endpoint. Participants with or without evidence of prior infection were included in the analysis.'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

At 1 month after dose 4

Notes
[98] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	14	9
Units: Percentage of participants
number (confidence interval 95%)	64.3 (35.1 to 87.2)	77.8 (40.0 to 97.2)

No statistical analyses for this end point

Secondary: SSB: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at 1 Month After Dose 3: Group 1 Only

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End point title

SSB: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at 1 Month After Dose 3: Group 1 Only ^[99]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before Dose 3). If the baseline measurement was below the LLOQ, the postvaccination assay result of >= 4*LLOQ was considered a seroresponse. Evaluable immunogenicity population (third dose) included all eligible participants who received first study intervention as third dose to which they were assigned, had at least one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the third dose, and had no other important protocol deviations as determined by the clinician. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse to SARS-CoV-2 omicron BA.4/BA.5–neutralizing titers at 1 month after dose 3 was reported in this endpoint. Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

1 month after dose 3

Notes
[99] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	11	10
Units: Percentage of participants
number (confidence interval 95%)	45.5 (16.7 to 76.6)	70.0 (34.8 to 93.3)

No statistical analyses for this end point

Secondary: SSB: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at 1 Month After Dose 4: Group 1 Only

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End point title

SSB: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at 1 Month After Dose 4: Group 1 Only ^[100]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before Dose 3). If the baseline measurement was below the LLOQ, the postvaccination assay result of >= 4*LLOQ was considered a seroresponse. Evaluable immunogenicity population (fourth dose) included all eligible participants who received 2 doses of the study intervention as third and fourth dose to which they were assigned, had at least one valid and determinate immunogenicity result from the blood sample collected within 28-42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse to SARS-CoV-2 omicron BA.4/BA.5–neutralizing titers at 1 month after dose 3 and 1 month after dose 4 was reported in this endpoint. Participants with or without evidence of prior infection were included in the analysis. 'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

At 1 month after dose 4

Notes
[100] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSB; hence, only arms for SSB were included.

End point values	SSB: Group 1a: 2 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2
Number of subjects analysed	14	9
Units: Percentage of participants
number (confidence interval 95%)	78.6 (49.2 to 95.3)	88.9 (51.8 to 99.7)

No statistical analyses for this end point

Secondary: SSD: Geometric Mean Titers (GMT) of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at Baseline and 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3)

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End point title

SSD: Geometric Mean Titers (GMT) of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at Baseline and 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3) ^[101]

End point description

GMT of SARS-CoV-2 Omicron strain–neutralizing titers at 1 month after the study vaccination was reported in this endpoint. 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). Assay results below the LLOQ were set to 0.5 × LLOQ. Evaluable immunogenicity population was analyzed. Results include those from a comparator group of C4591007 (NCT04816643) Phase 2/3 participants of the same age who received 3 doses of original BNT162b2 10 μg as of the data cutoff date of 27 May 2022.Participants with or without evidence of prior infection were included in the analysis.'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

Group 2: Baseline and 1 month after Dose 4; C4591007 control arm: Baseline and 1 month after Dose 3

Notes
[101] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSD; hence, only arms for SSD were included.

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 mcg
Number of subjects analysed	102	113
Units: Titers
geometric mean (confidence interval 95%)
Baseline (n=102,112)	488.3 (361.9 to 658.8)	248.3 (187.2 to 329.5)
1 Month (n=102,113)	2189.9 (1742.8 to 2751.7)	1393.6 (1175.8 to 1651.7)

No statistical analyses for this end point

Secondary: SSD: Geometric Mean Titers (GMT) of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Baseline and 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3)

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End point title

SSD: Geometric Mean Titers (GMT) of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Baseline and 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3) ^[102]

End point description

GMT of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 1 month after study vaccination was reported in this endpoint.GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers & the corresponding CIs(based on Student's t distribution).Assay results below the LLOQ were set to 0.5 × LLOQ.Evaluable immunogenicity population was analyzed. Results include those from a comparator group of C4591007(NCT04816643) Phase 2/3 participants of the same age who received 3 doses of original BNT162b2 10 μg as of the data cutoff date of 27 May 2022.Participants with or without evidence of prior infection were included in the analysis.'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

Group 2: Baseline and 1 month after Dose 4; C4591007 control arm: Baseline and 1 month after Dose 3

Notes
[102] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSD; hence, only arms for SSD were included.

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 mcg
Number of subjects analysed	102	113
Units: Titers
geometric mean (confidence interval 95%)
Baseline	2904.0 (2372.6 to 3554.5)	1323.1 (1055.7 to 1658.2)
1 Month	8245.9 (7108.9 to 9564.9)	7235.1 (6331.5 to 8267.8)

No statistical analyses for this end point

Secondary: SSD: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3)

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End point title

SSD: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3) ^[103]

End point description

GMFR of SARS-CoV-2 omicron BA.4/BA.5-neutralizing titers at 1 month after study vaccination was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis. Evaluable immunogenicity population was analyzed. Results include those from a comparator group of C4591007 (NCT04816643) Phase 2/3 participants of the same age who received 3 doses of original BNT162b2 10 μg as of the data cutoff date of 27 May 2022.Participants with or without evidence of prior infection were included in the analysis.'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

1 month after Dose 4 for Group 2 and 1 month after Dose 3 for C4591007 control arm

Notes
[103] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSD; hence, only arms for SSD were included.

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 mcg
Number of subjects analysed	101	112
Units: Fold rise
geometric mean (confidence interval 95%)	4.5 (3.8 to 5.4)	5.6 (4.5 to 6.9)

No statistical analyses for this end point

Secondary: SSD: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3)

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End point title

SSD: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3) ^[104]

End point description

GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 1 month after study vaccination was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis.Evaluable immunogenicity population was analyzed. Results include those from a comparator group of C4591007 (NCT04816643) Phase 2/3 participants of the same age who received 3 doses of original BNT162b2 10 μg as of the data cutoff date of 27 May 2022.Participants with or without evidence of prior infection were included in the analysis.'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

1 month after Dose 4 for Group 2 and 1 month after Dose 3 for C4591007 control arm

Notes
[104] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSD; hence, only arms for SSD were included.

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 mcg
Number of subjects analysed	101	113
Units: Fold rise
geometric mean (confidence interval 95%)	2.8 (2.5 to 3.3)	5.5 (4.5 to 6.7)

No statistical analyses for this end point

Secondary: SSD: Percentages of Participants With Seroresponse to SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3)

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End point title

SSD: Percentages of Participants With Seroresponse to SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers at 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3) ^[105]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before Dose 4 for C4591048 Substudy D Group 2 and before Dose 3 for C4591007). If the baseline measurement was below the lower limit of quantification (LLOQ), the postvaccination assay result of >= 4 ×* LLOQ was considered a seroresponse. Exact 2-sided 95% CI, based on the Clopper and Pearson method. Percentage of participants achieving seroresponse at 1 month after study vaccination was reported in this endpoint. Evaluable immunogenicity population was analyzed. Results include those from a comparator group of C4591007 (NCT04816643) Phase 2/3 participants of the same age who received 3 doses of original BNT162b2 10 μg as of the data cutoff date of 27 May 2022.Participants with or without evidence of prior infection were included in the analysis.'N'=participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

1 month after Dose 4 for Group 2 and 1 month after Dose 3 for C4591007 control arm

Notes
[105] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSD; hence, only arms for SSD were included.

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 mcg
Number of subjects analysed	101	112
Units: Percentage of participants
number (confidence interval 95%)	53.5 (43.3 to 63.5)	52.7 (43.0 to 62.2)

No statistical analyses for this end point

Secondary: SSE: GMT of SARS-CoV-2 Omicron XBB.1.5–Neutralizing Titers Before Vaccination and 1 Month After Vaccination

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End point title

SSE: GMT of SARS-CoV-2 Omicron XBB.1.5–Neutralizing Titers Before Vaccination and 1 Month After Vaccination ^[106]

End point description

GMT of SARS-CoV-2 omicron XBB.1.5 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). Assay results below the LLOQ were set to 0.5 *LLOQ. Evaluable immunogenicity population: All eligible participants who had received the study intervention to which they are assigned, had at least 1 valid and determinate immunogenicity results from the blood sample collected within 28 to 42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. 'N'=number of participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

Before Vaccination and 1 Month after Study Vaccination

Notes
[106] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSE; hence, only arms for SSE were included.

End point values	SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg
Number of subjects analysed	285
Units: Titer
geometric mean (confidence interval 95%)
Before Vaccination	195.0 (163.2 to 233.0)
1 Month after Study Vaccination	5930.5 (5283.8 to 6656.4)

No statistical analyses for this end point

Secondary: SSE: GMFR of SARS-CoV-2 Omicron XBB.1.5–Neutralizing Titers From Before Study Vaccination to 1 Month After Vaccination

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End point title

SSE: GMFR of SARS-CoV-2 Omicron XBB.1.5–Neutralizing Titers From Before Study Vaccination to 1 Month After Vaccination ^[107]

End point description

GMFR of SARS-CoV-2 omicron XBB.1.5 neutralizing titers from study vaccination to 1 month after study vaccination was reported in this outcome measure. GMFRs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5*LLOQ in the analysis. Evaluable immunogenicity population: All eligible participants who had received the study intervention to which they are assigned, had at least 1 valid and determinate immunogenicity results from the blood sample collected within 28 to 42 days after the study vaccination, and had no other important protocol deviations as determined by the clinician. 'N'=number of participants evaluable for this endpoint.

End point type

Secondary

End point timeframe

From before study vaccination to 1 month after study vaccination

Notes
[107] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is specific to SSE; hence, only arms for SSE were included.

End point values	SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg
Number of subjects analysed	285
Units: Fold Rise
number (confidence interval 95%)	30.4 (25.3 to 36.5)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Local reactions/systemic events(systematic assessment):upto Day(D)7 after vaccination.Non-SAEs(non-systematic assessment):From D1-1 month(M)after study vaccination.For All-cause mortality/SAE (non-systematic assessment) from D1-6M after study vaccination.

Adverse event reporting additional description

Same event may appear as both non-SAE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and non-serious in another participants, or one participant may have experienced both serious and non-serious event during the study. MedDRA version used for sub-study E is 27.0

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

SSD: Group 1: 2 prior doses of BNT162b2

Reporting group description

Reporting group title

SSD: Group 2: 3 prior doses of BNT162b2

Reporting group description

Participants aged 5 to 11 years who had received three prior doses of BNT162b2 10 mcg 90 to 240 days before enrollment in the study were included. Participants received a single dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Reporting group title

SSD: Group 3: Participants from study C4591007 Phase 1

Reporting group description

Participants from C4591007 phase 1 trial, aged 5 to 11 years who had received three prior doses of BNT162b2 10 mcg at least 90 days before enrollment in the study were included. Participants received a single dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Reporting group title

SSC: Group 1a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSC: Group 1b: 3 prior doses of BNT162b2

Reporting group description

Participants aged >=6 months to <2 years who had received three prior doses of BNT162b2 3 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single (fourth) dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Reporting group title

SSC: Group 2a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSC: Group 2b: 3 prior doses of BNT162b2

Reporting group description

Participants aged >=2 to <5 years who had received three prior doses of BNT162b2 3 mcg with the last dose received 60 to 240 days before enrollment in the study were included. Participants received a single (fourth) dose of BNT162b2 10 mcg via intramuscular route on Day 1 of the study.

Reporting group title

SSB: Group 1a: 2 prior doses of BNT162b2 (First Vaccination)

Reporting group description

Reporting group title

SSB: Group 3a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 1b: 2 prior doses of BNT162b2 (First Vaccination)

Reporting group description

Reporting group title

SSB: Group 1a: 2 prior doses of BNT162b2 (Second Vaccination)

Reporting group description

Reporting group title

SSB: Group 1b: 2 prior doses of BNT162b2 (Second Vaccination)

Reporting group description

Reporting group title

SSB: Group 2a: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 2b: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSB: Group 3b: 3 prior doses of BNT162b2

Reporting group description

Reporting group title

SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg

Reporting group description

Participants aged 5 to 11 years who received a single dose of BNT162b2 (Omi XBB.1.5) 10 mcg via intramuscular route on Day 1 of this sub-study.

SSD: Group 1: 2 prior doses of BNT162b2

SSD: Group 2: 3 prior doses of BNT162b2

SSD: Group 3: Participants from study C4591007 Phase 1

SSC: Group 1a: 3 prior doses of BNT162b2

SSC: Group 1b: 3 prior doses of BNT162b2

SSC: Group 2a: 3 prior doses of BNT162b2

SSC: Group 2b: 3 prior doses of BNT162b2

SSB: Group 1a: 2 prior doses of BNT162b2 (First Vaccination)

SSB: Group 3a: 3 prior doses of BNT162b2

SSB: Group 1b: 2 prior doses of BNT162b2 (First Vaccination)

SSB: Group 1a: 2 prior doses of BNT162b2 (Second Vaccination)

SSB: Group 1b: 2 prior doses of BNT162b2 (Second Vaccination)

SSB: Group 2a: 3 prior doses of BNT162b2

SSB: Group 2b: 3 prior doses of BNT162b2

SSB: Group 3b: 3 prior doses of BNT162b2

SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

1 / 218 (0.46%)

11 / 989 (1.11%)

3 / 310 (0.97%)

number of deaths (all causes)

number of deaths resulting from adverse events

Injury, poisoning and procedural complications

Post procedural haemorrhage

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

1 / 989 (0.10%)

0 / 310 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Seizure

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

0 / 989 (0.00%)

1 / 310 (0.32%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Hypothermia

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

1 / 989 (0.10%)

0 / 310 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Faecaloma

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

1 / 989 (0.10%)

0 / 310 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

1 / 989 (0.10%)

0 / 310 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Asthma

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

2 / 989 (0.20%)

0 / 310 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchial hyperreactivity

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

1 / 989 (0.10%)

0 / 310 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Breathing-related sleep disorder

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

1 / 218 (0.46%)

0 / 989 (0.00%)

0 / 310 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Mental status changes

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

1 / 989 (0.10%)

0 / 310 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Cellulitis

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

1 / 989 (0.10%)

0 / 310 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia viral

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

1 / 989 (0.10%)

0 / 310 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

1 / 989 (0.10%)

0 / 310 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Viral upper respiratory tract infection

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

1 / 989 (0.10%)

0 / 310 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

0 / 989 (0.00%)

2 / 310 (0.65%)

occurrences causally related to treatment / all

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Dehydration

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

1 / 989 (0.10%)

0 / 310 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperglycaemia

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 19 (0.00%)

0 / 17 (0.00%)

0 / 19 (0.00%)

0 / 32 (0.00%)

0 / 30 (0.00%)

0 / 17 (0.00%)

0 / 68 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (0.00%)

0 / 92 (0.00%)

0 / 218 (0.00%)

1 / 989 (0.10%)

0 / 310 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	SSD: Group 1: 2 prior doses of BNT162b2	SSD: Group 2: 3 prior doses of BNT162b2	SSD: Group 3: Participants from study C4591007 Phase 1	SSC: Group 1a: 3 prior doses of BNT162b2	SSC: Group 1b: 3 prior doses of BNT162b2	SSC: Group 2a: 3 prior doses of BNT162b2	SSC: Group 2b: 3 prior doses of BNT162b2	SSB: Group 1a: 2 prior doses of BNT162b2 (First Vaccination)	SSB: Group 3a: 3 prior doses of BNT162b2	SSB: Group 1b: 2 prior doses of BNT162b2 (First Vaccination)	SSB: Group 1a: 2 prior doses of BNT162b2 (Second Vaccination)	SSB: Group 1b: 2 prior doses of BNT162b2 (Second Vaccination)	SSB: Group 2a: 3 prior doses of BNT162b2	SSB: Group 2b: 3 prior doses of BNT162b2	SSB: Group 3b: 3 prior doses of BNT162b2	SSE: Monovalent BNT162b2 (Omi XBB.1.5) 10 mcg
Total subjects affected by non serious adverse events
subjects affected / exposed	1 / 2 (50.00%)	88 / 113 (77.88%)	16 / 19 (84.21%)	13 / 17 (76.47%)	17 / 19 (89.47%)	24 / 32 (75.00%)	17 / 30 (56.67%)	14 / 17 (82.35%)	44 / 68 (64.71%)	7 / 13 (53.85%)	11 / 17 (64.71%)	5 / 13 (38.46%)	48 / 92 (52.17%)	130 / 218 (59.63%)	532 / 989 (53.79%)	164 / 310 (52.90%)
Injury, poisoning and procedural complications
Animal bite
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	1 / 19 (5.26%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Arthropod bite
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Skin abrasion
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 92 (1.09%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Contusion
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	1 / 68 (1.47%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Nervous system disorders
Headache (HEADACHE)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	28 / 113 (24.78%)	7 / 19 (36.84%)	0 / 17 (0.00%)	0 / 19 (0.00%)	4 / 32 (12.50%)	1 / 30 (3.33%)	0 / 17 (0.00%)	0 / 68 (0.00%)	1 / 13 (7.69%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	9 / 218 (4.13%)	43 / 989 (4.35%)	43 / 310 (13.87%)
occurrences all number	0	28	7	0	0	4	1	0	0	1	0	0	0	9	43	43
Somnolence (DROWSINESS)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	5 / 17 (29.41%)	5 / 19 (26.32%)	0 / 32 (0.00%)	0 / 30 (0.00%)	7 / 17 (41.18%)	11 / 68 (16.18%)	0 / 13 (0.00%)	2 / 17 (11.76%)	0 / 13 (0.00%)	18 / 92 (19.57%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	5	5	0	0	7	11	0	2	0	18	0	0	0
Somnolence
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
General disorders and administration site conditions
Chills (CHILLS)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	10 / 113 (8.85%)	2 / 19 (10.53%)	0 / 17 (0.00%)	0 / 19 (0.00%)	4 / 32 (12.50%)	1 / 30 (3.33%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	10 / 218 (4.59%)	24 / 989 (2.43%)	17 / 310 (5.48%)
occurrences all number	0	10	2	0	0	4	1	0	0	0	0	0	0	10	24	17
Fatigue (FATIGUE)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	45 / 113 (39.82%)	11 / 19 (57.89%)	0 / 17 (0.00%)	0 / 19 (0.00%)	13 / 32 (40.63%)	11 / 30 (36.67%)	0 / 17 (0.00%)	0 / 68 (0.00%)	4 / 13 (30.77%)	0 / 17 (0.00%)	3 / 13 (23.08%)	0 / 92 (0.00%)	68 / 218 (31.19%)	283 / 989 (28.61%)	45 / 310 (14.52%)
occurrences all number	0	45	11	0	0	13	11	0	0	4	0	3	0	68	283	45
Injection site erythema (REDNESS)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	8 / 113 (7.08%)	2 / 19 (10.53%)	4 / 17 (23.53%)	4 / 19 (21.05%)	2 / 32 (6.25%)	1 / 30 (3.33%)	1 / 17 (5.88%)	4 / 68 (5.88%)	1 / 13 (7.69%)	2 / 17 (11.76%)	0 / 13 (0.00%)	7 / 92 (7.61%)	14 / 218 (6.42%)	100 / 989 (10.11%)	18 / 310 (5.81%)
occurrences all number	0	8	2	4	4	2	1	1	4	1	2	0	7	14	100	18
Injection site haemorrhage
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	1 / 19 (5.26%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Injection site pain (PAIN)
alternative assessment type: Systematic
subjects affected / exposed	1 / 2 (50.00%)	71 / 113 (62.83%)	13 / 19 (68.42%)	1 / 17 (5.88%)	3 / 19 (15.79%)	10 / 32 (31.25%)	8 / 30 (26.67%)	0 / 17 (0.00%)	0 / 68 (0.00%)	4 / 13 (30.77%)	0 / 17 (0.00%)	1 / 13 (7.69%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	129 / 310 (41.61%)
occurrences all number	1	71	13	1	3	10	8	0	0	4	0	1	0	0	0	129
Fatigue
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	1 / 68 (1.47%)	0 / 13 (0.00%)	0 / 17 (0.00%)	1 / 13 (7.69%)	1 / 92 (1.09%)	0 / 218 (0.00%)	2 / 989 (0.20%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	1	1	0	2	0
Pyrexia
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	1 / 32 (3.13%)	0 / 30 (0.00%)	1 / 17 (5.88%)	2 / 68 (2.94%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 92 (1.09%)	3 / 218 (1.38%)	8 / 989 (0.81%)	0 / 310 (0.00%)
occurrences all number	0	0	0	1	0	1	0	1	2	0	0	0	2	3	8	0
Pyrexia (FEVER)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	5 / 113 (4.42%)	2 / 19 (10.53%)	3 / 17 (17.65%)	1 / 19 (5.26%)	8 / 32 (25.00%)	3 / 30 (10.00%)	0 / 17 (0.00%)	7 / 68 (10.29%)	0 / 13 (0.00%)	2 / 17 (11.76%)	0 / 13 (0.00%)	8 / 92 (8.70%)	15 / 218 (6.88%)	51 / 989 (5.16%)	14 / 310 (4.52%)
occurrences all number	0	5	2	3	1	8	3	0	7	0	2	0	8	15	51	14
Injection site swelling
subjects affected / exposed	0 / 2 (0.00%)	5 / 113 (4.42%)	2 / 19 (10.53%)	0 / 17 (0.00%)	0 / 19 (0.00%)	2 / 32 (6.25%)	0 / 30 (0.00%)	0 / 17 (0.00%)	1 / 68 (1.47%)	1 / 13 (7.69%)	1 / 17 (5.88%)	0 / 13 (0.00%)	5 / 92 (5.43%)	9 / 218 (4.13%)	39 / 989 (3.94%)	0 / 310 (0.00%)
occurrences all number	0	5	2	0	0	2	0	0	1	1	1	0	5	9	39	0
Injection site erythema
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	1 / 68 (1.47%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Chills
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	1 / 68 (1.47%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Injection site pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 92 (1.09%)	1 / 218 (0.46%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0
Injection site pain (TENDERNESS)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	8 / 68 (11.76%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	10 / 92 (10.87%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	8	0	0	0	10	0	0	0
Injection site swelling (SWELLING)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	28 / 310 (9.03%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	28
Gastrointestinal disorders
Vomiting
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	3 / 68 (4.41%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	2 / 92 (2.17%)	1 / 218 (0.46%)	7 / 989 (0.71%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	3	0	0	0	2	1	7	0
Vomiting (VOMITING)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	4 / 113 (3.54%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	3 / 32 (9.38%)	2 / 30 (6.67%)	0 / 17 (0.00%)	0 / 68 (0.00%)	1 / 13 (7.69%)	0 / 17 (0.00%)	1 / 13 (7.69%)	0 / 92 (0.00%)	11 / 218 (5.05%)	47 / 989 (4.75%)	13 / 310 (4.19%)
occurrences all number	0	4	0	0	0	3	2	0	0	1	0	1	0	11	47	13
Diarrhea (DIARRHEA)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	4 / 113 (3.54%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	2 / 32 (6.25%)	1 / 30 (3.33%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	1 / 13 (7.69%)	0 / 92 (0.00%)	11 / 218 (5.05%)	68 / 989 (6.88%)	22 / 310 (7.10%)
occurrences all number	0	4	0	0	0	2	1	0	0	0	0	1	0	11	68	22
Diarrhoea
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	2 / 92 (2.17%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0
Respiratory, thoracic and mediastinal disorders
Nasal congestion
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	1 / 68 (1.47%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	1 / 989 (0.10%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0
Tachypnoea
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	1 / 68 (1.47%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Cough
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	1 / 68 (1.47%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	2 / 989 (0.20%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	2	0
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	1 / 32 (3.13%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Erythema
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	1 / 19 (5.26%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	1 / 68 (1.47%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 92 (1.09%)	1 / 218 (0.46%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0	0	1	1	0	0
Rash maculo-papular
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	1 / 68 (1.47%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	1 / 19 (5.26%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Irritability
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	8 / 17 (47.06%)	14 / 19 (73.68%)	0 / 32 (0.00%)	0 / 30 (0.00%)	11 / 17 (64.71%)	29 / 68 (42.65%)	0 / 13 (0.00%)	9 / 17 (52.94%)	0 / 13 (0.00%)	32 / 92 (34.78%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	8	14	0	0	11	29	0	9	0	32	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	10 / 113 (8.85%)	2 / 19 (10.53%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	14 / 310 (4.52%)
occurrences all number	0	10	2	0	0	0	0	0	0	0	0	0	0	0	0	14
Myalgia
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	15 / 113 (13.27%)	4 / 19 (21.05%)	0 / 17 (0.00%)	0 / 19 (0.00%)	3 / 32 (9.38%)	2 / 30 (6.67%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	7 / 218 (3.21%)	20 / 989 (2.02%)	31 / 310 (10.00%)
occurrences all number	0	15	4	0	0	3	2	0	0	0	0	0	0	7	20	31
Pain in extremity
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	1 / 17 (5.88%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Infections and infestations
Upper respiratory tract infections
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	1 / 19 (5.26%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 92 (1.09%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Otitis media
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 32 (0.00%)	1 / 30 (3.33%)	0 / 17 (0.00%)	1 / 68 (1.47%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	3 / 989 (0.30%)	0 / 310 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	1	0	0	0	0	0	3	0
Gastroenteritis
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	1 / 17 (5.88%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Ear infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 92 (1.09%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Impetigo
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	0 / 68 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	1 / 92 (1.09%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Pharyngitis streptococcal
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	0 / 17 (0.00%)	0 / 19 (0.00%)	0 / 32 (0.00%)	0 / 30 (0.00%)	0 / 17 (0.00%)	1 / 68 (1.47%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	0 / 92 (0.00%)	0 / 218 (0.00%)	2 / 989 (0.20%)	0 / 310 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	2	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 19 (0.00%)	4 / 17 (23.53%)	3 / 19 (15.79%)	0 / 32 (0.00%)	0 / 30 (0.00%)	4 / 17 (23.53%)	13 / 68 (19.12%)	0 / 13 (0.00%)	3 / 17 (17.65%)	0 / 13 (0.00%)	18 / 92 (19.57%)	0 / 218 (0.00%)	0 / 989 (0.00%)	0 / 310 (0.00%)
occurrences all number	0	0	0	4	3	0	0	4	13	0	3	0	18	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

21 Oct 2022

Amendment 1: SSB: Updated section 1.1 Increased samples size in Group 2 to 300 and Group 3 to 3600; Decreased the number of days since last dose prior to enrollment in Group 3 to 60 days;Removed restriction on Group 3 that only participants from the C4591007 study in Phase 1 could participate; Updated section 10.8.3: Updated and added objectives, estimands, and endpoints to demonstrate noninferiority with respect to the level of neutralizing titers and the seroresponse rate of the anti–reference-strain immune response;Updated Section 10.8.9.1.2: Added multiplicity adjustment method for evaluating superiority and noninferiority with respect to level of neutralizing titer for GMR and seroresponse rate; Updated Section 10.8.9.3.2:Clarified immunogenicity endpoint analysis and success criterion for newly added superiority and noninferiority of anti–Omicron BA.4/BA.5 immune response objective;Updated Section 10.8.9.5 Added sample size and power calculation for the newly added superiority and noninferiority of anti- Omicron and anti–reference-strain immune response objectives SSD: Updated section 1.1 :Decreased the number of days since last dose prior to enrollment in Group 3 to 90 days. Updated Sections 10.7.5.2, 10.8.5.2, 10.9.5.2, 10.10.5.2 Exclusion Criteria Substudy A, B, C, D: Added radiotherapy,within 60 days before enrollment. Updated section 10.10.3 Clarified that the primary immunogenicity comparison would be between the SSD Group 1 to C4591007 Phase 2/3 participants and made editorial change to the estimands. Updated section 10.10.1.2: Removed 1-month postdose blood draw group 3 only. Updated section 10.10.1.3.2: Added the group numbers to rows specific to blood sample collection. Updated section 10.10.1.3.2: Added row specific to Group 3 blood draw to be collected at baseline only.

18 Nov 2022

Amendment 2: Updated high-level overview table to reflect Substudy C updates Section 1.1 Synopsis; Updated Substudy C study design text to reflect defined age groups and update to sample size in Section 1.1 Synopsis, Section 10.9.1.2 Schema, Section 10.9.4.1 Overall Design, Section 10.9.6.4 Blinding; Clarified AE reporting guidance for potential COVID-19/MIS-C illnesses and their sequelae to be consistent with Section 8.4.7

01 Aug 2023

Amendment 3: SSB: Updated Section 10.8.3: Added a secondary immunogenicity endpoint for SARS-CoV-2 reference-strain– neutralizing titers(previously omitted) SSC: Updated Section 10.9 Removed all references to the Phase 2/3 portion of Substudy C;Updated Section 10.9.1 Updated expanded enrollment numbers in Substudy C Phase 1 to reflect actual enrollment figures SSD: Updated section: 10.10.3: Added “at 1 month after Dose 4” to the second primary immunogenicity objective.

01 Sep 2023

Amendment 4:SSB: Updated Section 10.8.3 and Section 10.8.9.3.2 Removed objectives for immunogenicity comparisons related to Group 1. Section 10.8.9.2 Corrected the description of the all-available immunogenicity population to reflect all assigned participants instead of all randomized participants.SSC: Updated Section 10.9.3 and Section 10.9.9.3. Removed the analysis across both age groups combined. 2SSD: Updated section 10.10.3 and 10.10.9.3.2: Removed objectives for immunogenicity comparisons and descriptive summaries related to Group 1. Added a new Substudy E to evaluate a single dose of BNT162b2 (Omi XBB.1.5) in COVID-19 vaccine–naïve individuals >=2 to 12 years of age.

05 Jul 2024

Amendment 5: Updated Substudy E primary and secondary objectives, statistical hypotheses, and the primary, secondary, and tertiary endpoints, estimands, and analyses Updated Section 10.11.3 Objectives, Estimands, and Endpoints, Section 10.11.9.1 Statistical Hypotheses, and Section 10.11.9.3 Statistical Analyses. updated inclusion and exclusion criteria for Substudy E; Updated Section 10.7.5.2 Exclusion Criteria, Section 10.11.5.1 Inclusion Criteria, and Section 10.11.5.2 Exclusion Criteria; Updated the timing of the statistical analyses for Substudy E Section 10.11.9.4.1 Analysis Timing Updated Substudy E immunogenicity assessments Updated Section 10.11.9.5 Sample Size Determination

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Master Phase 1/2/3 Protocol to Investigate the Safety, Tolerability, and Immunogenicity of Variant- Adapted BNT162b2 RNA-Based Vaccine Candidate (s) in Healthy Children

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 1 in Participants Aged >=6 months to <2 Years

Primary: SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 1 in Participants Aged >=6 months to <2 Years

Primary: SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 2 in Participants Aged >=6 months to <2 Years: Group 1a Only

Primary: SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 2 in Participants Aged >=6 months to <2 Years: Group 1a Only

Primary: SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 1 in Participants Aged >=6 months to <2 Years

Primary: SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 1 in Participants Aged >=6 months to <2 Years

Primary: SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 2 in Participants Aged >=6 months to <2 Years: Group 1a Only

Primary: SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 2 in Participants Aged >=6 months to <2 Years: Group 1a Only

Primary: SSB: Percentage of Participants Reporting Adverse Events (AEs) From the First Study Vaccination to 1 Month After Study Vaccination 1 in Participants Aged >=6 Months to <2 Years

Primary: SSB: Percentage of Participants Reporting Adverse Events (AEs) From the First Study Vaccination to 1 Month After Study Vaccination 1 in Participants Aged >=6 Months to <2 Years

Primary: SSB: Percentage of Participants Reporting Adverse Events (AEs) From the Second Study Vaccination to 1 Month After Study Vaccination 2 in Participants Aged >=6 Months to <2 Years: Group 1a Only

Primary: SSB: Percentage of Participants Reporting Adverse Events (AEs) From the Second Study Vaccination to 1 Month After Study Vaccination 2 in Participants Aged >=6 Months to <2 Years: Group 1a Only

Primary: SSB: Percentage of Participants Reporting Serious Adverse Events (SAEs) From the Study Vaccination to 6 Months After Last Study Vaccination in Participants Aged >=6 Months to <2 Years

Primary: SSB: Percentage of Participants Reporting Serious Adverse Events (SAEs) From the Study Vaccination to 6 Months After Last Study Vaccination in Participants Aged >=6 Months to <2 Years

Primary: SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 2 in Participants Aged >=2 to <5 Years: Group 1b Only

Primary: SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 2 in Participants Aged >=2 to <5 Years: Group 1b Only

Primary: SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 1 in Participants Aged >=2 to <5 Years

Primary: SSB: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination 1 in Participants Aged >=2 to <5 Years

Primary: SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 1 in Participants Aged >=2 to <5 Years

Primary: SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 1 in Participants Aged >=2 to <5 Years

Primary: SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 2 in Participants Aged >=2 to <5 Years: Group 1b Only

Primary: SSB: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination 2 in Participants Aged >=2 to <5 Years: Group 1b Only

Primary: SSB: Percentage of Participants Reporting AEs From the First Study Vaccination to 1 Month After Study Vaccination 1 in Participants Aged >=2 to <5 Years

Primary: SSB: Percentage of Participants Reporting AEs From the First Study Vaccination to 1 Month After Study Vaccination 1 in Participants Aged >=2 to <5 Years

Primary: SSB: Percentage of Participants Reporting AEs From the Second Study Vaccination to 1 Month After Study Vaccination 2 in Participants Aged >=2 to <5 Years: Group 1b Only

Primary: SSB: Percentage of Participants Reporting AEs From the Second Study Vaccination to 1 Month After Study Vaccination 2 in Participants Aged >=2 to <5 Years: Group 1b Only

Primary: SSB: Percentage of Participants Reporting SAEs From the First Study Vaccination to 6 Months After Last Study Vaccination in Participants Aged >=2 to <5 Years

Primary: SSB: Percentage of Participants Reporting SAEs From the First Study Vaccination to 6 Months After Last Study Vaccination in Participants Aged >=2 to <5 Years

Primary: SSB: GMR Based on Geometric Mean Titers of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‑CoV‑2) Omicron (BA.4/BA.5)–Neutralizing Titers at 1 Month After Dose 4 for Group 2 and at 1 Month After Dose 3 for C4591007 Phase 2/3 Participants

Primary: SSB: GMR Based on Geometric Mean Titers of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‑CoV‑2) Omicron (BA.4/BA.5)–Neutralizing Titers at 1 Month After Dose 4 for Group 2 and at 1 Month After Dose 3 for C4591007 Phase 2/3 Participants

Primary: SSB: Percentage of Participants With Seroresponse to the Omicron (BA.4/BA.5)–Strain at 1 Month After Dose 4 for Group 2 and at 1 Month After Dose 3 for C4591007 Phase 2/3 Participants

Primary: SSB: Percentage of Participants With Seroresponse to the Omicron (BA.4/BA.5)–Strain at 1 Month After Dose 4 for Group 2 and at 1 Month After Dose 3 for C4591007 Phase 2/3 Participants

Primary: SSC: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination in Participants Aged >=6 Months to <2 Years

Primary: SSC: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination in Participants Aged >=6 Months to <2 Years

Primary: SSC: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination in Participants Aged >=6 Months to <2 Years

Primary: SSC: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination in Participants Aged >=6 Months to <2 Years

Primary: SSC: Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination in Participants Aged >=6 Months to <2 Years

Primary: SSC: Percentage of Participants Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination in Participants Aged >=6 Months to <2 Years

Primary: SSC: Percentage of Participants Reporting Serious Adverse Events (SAEs) Within 6 Months After Study Vaccination in Participants Aged >=6 Months to <2 Years

Primary: SSC: Percentage of Participants Reporting Serious Adverse Events (SAEs) Within 6 Months After Study Vaccination in Participants Aged >=6 Months to <2 Years

Primary: SSC: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination in Participants Aged >=2 to <5 Years

Primary: SSC: Percentage of Participants With Local Reactions Within 7 Days After Study Vaccination in Participants Aged >=2 to <5 Years

Primary: SSC: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination in Participants Aged >=2 to <5 Years

Primary: SSC: Percentage of Participants With Systemic Events Within 7 Days After Study Vaccination in Participants Aged >=2 to <5 Years

Primary: SSC: Percentage of Participants Reporting AEs Within 1 Month After Study Vaccination in Participants Aged >=2 to <5 Years

Primary: SSC: Percentage of Participants Reporting AEs Within 1 Month After Study Vaccination in Participants Aged >=2 to <5 Years

Primary: SSC: Geometric Mean Titers of SARS‑CoV‑2 Omicron (BA.4/BA.5)–Neutralizing Titers Before Vaccination and 1 Month After Vaccination

Primary: SSC: Geometric Mean Titers of SARS‑CoV‑2 Omicron (BA.4/BA.5)–Neutralizing Titers Before Vaccination and 1 Month After Vaccination

Primary: SSC: Percentage of Participants Reporting SAEs Within 6 Months After Study Vaccination in Participants Aged >=2 to <5 Years

Primary: SSC: Percentage of Participants Reporting SAEs Within 6 Months After Study Vaccination in Participants Aged >=2 to <5 Years

Primary: SSC: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers From Study Vaccination to 1 Month After Vaccination

Primary: SSC: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron BA.4/BA.5–Neutralizing Titers From Study Vaccination to 1 Month After Vaccination

Primary: SSC:Percentages of Participants With Seroresponse to the Omicron (BA.4/BA.5)– Neutralizing Titers at 1 Month After Study Vaccination

Primary: SSC:Percentages of Participants With Seroresponse to the Omicron (BA.4/BA.5)– Neutralizing Titers at 1 Month After Study Vaccination

Primary: SSC:Geometric Mean Titers of SARS‑CoV‑2 Reference-Strain-Neutralizing Titers Before Vaccination and 1 Month After Vaccination

Primary: SSC:Geometric Mean Titers of SARS‑CoV‑2 Reference-Strain-Neutralizing Titers Before Vaccination and 1 Month After Vaccination

Primary: SSC:GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Study Vaccination to 1 Month After Vaccination

Primary: SSC:GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Study Vaccination to 1 Month After Vaccination

Primary: SSC: Percentages of Participants With Seroresponse to the SARS-CoV-2 Reference Strain Neutralizing Titers at 1 Month After Study Vaccination

Primary: SSC: Percentages of Participants With Seroresponse to the SARS-CoV-2 Reference Strain Neutralizing Titers at 1 Month After Study Vaccination

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

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

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

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

Primary: SSD: Percentage of Participants Reporting Adverse Events (AEs) 1 Month After Study Vaccination

Primary: SSD: Percentage of Participants Reporting Adverse Events (AEs) 1 Month After Study Vaccination

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

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

Primary: SSD: Percentages of Participants With Seroresponse to the Omicron (BA.4/BA.5)– Neutralizing Titers at 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3)

Primary: SSD: Percentages of Participants With Seroresponse to the Omicron (BA.4/BA.5)– Neutralizing Titers at 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3)

Clinical Trial Results:
A Master Phase 1/2/3 Protocol to Investigate the Safety, Tolerability, and Immunogenicity of Variant- Adapted BNT162b2 RNA-Based Vaccine Candidate (s) in Healthy Children