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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 candidates(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	v2(current)
This version publication date	11 Jul 2024
First version publication date	06 Mar 2024
Other versions	v1
Version creation reason

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

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Trial information

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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

25 Oct 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Main objective of the trial

SSB:Safety&tolerability profiles of bivalent BNT162b2 given as 3rd and/or 4th dose in participants>=6 months to <5 years(6M-<5Y).Compare anti–Omicron BA.4/BA.5 immune response between participants(6M-<5Y) who received 3 prior doses of BNT162b2 3 μg&received BNT162b2 as 4th dose in Group 2&Study C4591007 Phase 2/3 participants who received 3 doses of BNT162b2 3 μg.SSC:Safety&tolerability profiles of prophylactic bivalent BNT162b2 at each dose level given as 4th dose in participants 6M-<5Y.Describe immune responses elicited by prophylactic bivalent BNT162b2 at each dose level given as 4th dose in participants 6M-<5Y.SSD:Safety&tolerability profiles of bivalent BNT162b2 given as 3rd or 4th dose in participants 5 to 12 years(5-12y).Compare the anti–Omicron BA.4/BA.5 immune response between participants(5-12y) who received 3 prior doses of BNT162b2 10 μg&received bivalent BNT162b2 as 4th dose in Group 2&Study C4591007 Phase 2/3 participants(5-12y)who received 3 doses of BNT162b2 10 μg.

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: 1610

Worldwide total number of subjects

1610

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)

1465

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

SSB:1398 participants enrolled, 1397 were vaccinated. SSC: 100 participants randomised, 98 were vaccinated.SSD: 136 participants enrolled and 134 were vaccinated.Data is reported at study completion date for SSB, SSC and SSD. PCD for SSA and SSE have not been reached;data collection is still ongoing, hence no data are reported for SSA and E.

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.

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
Started	17	13	92	218	68	989	17	19	32	30	2	113
Completed	17	13	92	218	68	989	17	19	32	30	2	113

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 Historical cohort: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

Active comparator

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.

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 Historical cohort:Participants from study C4591007 Phase 1
Started	17	13	92	218	68	989	2	113	19
Completed	17	11	89	210	67	969	2	111	19
Not completed	0	2	3	8	1	20	0	2	0
Physician decision	-	-	-	-	-	1	-	-	-
Consent withdrawn by subject	-	-	-	-	-	-	-	1	-
Withdrawal by parents/guardian	-	2	3	7	-	4	-	1	-
Lost to follow-up	-	-	-	-	1	12	-	-	-
Protocol deviation	-	-	-	1	-	3	-	-	-

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 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	Total
Number of subjects	17	13	92	218	68	989	17	19	32	30	2	113	1610
Age Categorical
Units: Participants
In utero	0	0	0	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	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
Infants and toddlers (28 days-23 months)	17	0	92	0	68	0	17	0	32	0	0	0	226
Children (2-11 years)	0	13	0	218	0	989	0	19	0	30	2	113	1384
Adolescents (12-17 years)	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
From 65-84 years	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
Gender Categorical
Units: Participants
Female	5	7	41	113	30	512	8	11	16	13	0	56	812
Male	12	6	51	105	38	477	9	8	16	17	2	57	798
Race
Units: Subjects
White	14	7	64	153	58	775	13	18	25	23	2	66	1218
Black or African American	0	0	2	7	5	51	0	1	2	1	0	9	78
Asian	1	4	11	18	3	57	2	0	2	3	0	13	114
Multiracial	1	2	15	39	2	100	2	0	3	3	0	22	189
Not reported	1	0	0	1	0	2	0	0	0	0	0	3	7
Native Hawaiian or other Pacific Islander	0	0	0	0	0	1	0	0	0	0	0	0	1
American Indian or Alaska Native	0	0	0	0	0	3	0	0	0	0	0	0	3
Ethinicity
Units: Subjects
Hispanic/Latino	3	2	18	34	12	136	2	2	1	0	0	23	233
Non-Hispanic/non-Latino	13	11	74	184	56	852	15	17	31	30	2	90	1375
Not reported	1	0	0	0	0	1	0	0	0	0	0	0	2

End points

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

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 Historical cohort:Participants from study C4591007 Phase 1

Reporting group description

Subject analysis set title

SSD Historical cohort: C4591007 BNT162b2 10 μg

Subject analysis set type

Per protocol

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

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

Subject analysis set type

Per protocol

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

Per protocol

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.

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]

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)

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: No statistical 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 (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 ^[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 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
[2] - 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: No statistical 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 (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 ^[3]

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
[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: No statistical 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 (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 (14.2 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

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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 ^[4]

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 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:ER visit/hospitalisation and 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.

End point type

Primary

End point timeframe

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

Notes
[4] - 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: No statistical 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 (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 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 ^[5]

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
[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: No statistical 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 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

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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 ^[6]

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
[6] - 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: No statistical 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 Adverse Events (AEs) From the First Study Vaccination to 1 Month After Study Vaccination 1 in Participants Aged >=6 Months to <2 Years

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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 ^[7]

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
[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: No statistical 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 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 ^[8]

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
[8] - 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: No statistical analysis was planned for this endpoint

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 ^[9]

End point description

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
[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: No statistical analysis was planned for this endpoint

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 ^[10]

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
[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: No statistical analysis was planned for this endpoint

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 ^[11]

End point description

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
[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: No statistical analysis was planned for this endpoint

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 ^[12]

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
[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: No statistical analysis was planned for this endpoint

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 ^[13]

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
[13] - 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: No statistical analysis was planned for this endpoint

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 ^[14]

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
[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: No statistical analysis was planned for this endpoint

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

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

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 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

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

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

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

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 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 ^[15]

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
[15] - 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 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 ^[16]

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
[16] - 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 ^[17]

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
[17] - 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: No statistical analysis was planned for this endpoint

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 ^[18]

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
[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: No statistical analysis was planned for this endpoint

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 ^[19]

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

Notes
[19] - 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: No statistical analysis was planned for this endpoint

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 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 ^[20]

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 subjects analyzed= participants evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination

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: No statistical analysis was planned for this endpoint

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 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 ^[21]

End point description

End point type

Primary

End point timeframe

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

Notes
[21] - 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: No statistical analysis was planned for this endpoint

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 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 ^[22]

End point description

End point type

Primary

End point timeframe

Day 1 up to Day 7 after study vaccination

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: No statistical analysis was planned for this endpoint

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 ^[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.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

Notes
[23] - 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: No statistical analysis was planned for this endpoint

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: 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 ^[24]

End point description

End point type

Primary

End point timeframe

From study vaccination on Day 1 up to 6 months after 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: No statistical analysis was planned for this endpoint

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: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 ^[25]

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
[25] - 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: No statistical analysis was planned for this endpoint

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 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 ^[26]

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
[26] - 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: No statistical analysis was planned for this endpoint

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: 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 ^[27]

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
[27] - 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: No statistical analysis was planned for this endpoint

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: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 ^[28]

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
[28] - 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: No statistical analysis was planned for this endpoint

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: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 ^[29]

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
[29] - 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: No statistical analysis was planned for this endpoint

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: 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 ^[30]

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
[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: No statistical analysis was planned for this endpoint

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 ^[31]

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 classified 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
[31] - 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: No statistical analysis was planned for this endpoint

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

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 ^[32]

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
[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: No statistical analysis was planned for this endpoint

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

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)

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 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

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 μg
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 difference in proportions 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] 10 μg - BNT162b2 10 μg). 2-Sided CI, based on the Miettinen and Nurminen method for the difference in proportions stratified 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 μg

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: 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 ^[33]

End point description

End point type

Primary

End point timeframe

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

Notes
[33] - 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: No statistical analysis was planned for this endpoint

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

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 ^[34]

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
[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: No statistical analysis was planned for this endpoint

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

No statistical analyses for this end point

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)

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

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 μg
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 μg

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

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

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

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

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

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

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

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 ^[35]

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
[35] - 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 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

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

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

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

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 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

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

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 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

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

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%)
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

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

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

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

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 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

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

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 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

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

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: 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

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

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 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

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

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

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

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

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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

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

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

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

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 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

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

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 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

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

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

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

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 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

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

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: 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

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

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: 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)

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

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 μg
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 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)

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

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 μg
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 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)

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

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 μg
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)

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

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 μg
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)

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

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 μg
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: SSD: Percentages of Participants With Seroresponse to 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: Percentages of Participants With Seroresponse to Reference-Strain-Neutralizing Titers at 1 Month After Dose 4 for Group 2 and C4591007 Phase 2/3 Participants (1 Month After Dose 3)

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.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

End point values	SSD: Group 2: 3 prior doses of BNT162b2	SSD Historical cohort: C4591007 BNT162b2 10 μg
Number of subjects analysed	101	113
Units: Percentage of participants
number (confidence interval 95%)	30.7 (21.9 to 40.7)	54.9 (45.2 to 64.2)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Local reactions/systemic events(systematic assessment):up to Day 7 after vaccination.Non-SAEs (non-systematic assessment):From Day 1 up to 1 month after study vaccination.For SAE (non-systematic assessment)from Day 1 to 6 months after study vaccination.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

26.1

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

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

Reporting group description

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 2b: 3 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 3b: 3 prior doses of BNT162b2

Reporting group description

SSD: Group 1: 2 prior doses of BNT162b2

SSD: Group 2: 3 prior doses of BNT162b2

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

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

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

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 2b: 3 prior doses of BNT162b2

SSB: Group 2a: 3 prior doses of BNT162b2‌

SSB: Group 3b: 3 prior doses of BNT162b2

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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%)

1 / 218 (0.46%)

0 / 92 (0.00%)

11 / 989 (1.11%)

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 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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 / 218 (0.00%)

0 / 92 (0.00%)

1 / 989 (0.10%)

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 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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 / 218 (0.00%)

0 / 92 (0.00%)

1 / 989 (0.10%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Faecaloma

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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 / 218 (0.00%)

0 / 92 (0.00%)

1 / 989 (0.10%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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 / 218 (0.00%)

0 / 92 (0.00%)

1 / 989 (0.10%)

occurrences causally related to treatment / all

0 / 0

0 / 1

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 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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 / 218 (0.00%)

0 / 92 (0.00%)

2 / 989 (0.20%)

occurrences causally related to treatment / all

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Bronchial hyperreactivity

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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 / 218 (0.00%)

0 / 92 (0.00%)

1 / 989 (0.10%)

occurrences causally related to treatment / all

0 / 0

0 / 1

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 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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%)

1 / 218 (0.46%)

0 / 92 (0.00%)

0 / 989 (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 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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 / 218 (0.00%)

0 / 92 (0.00%)

1 / 989 (0.10%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Infections and infestations

Cellulitis

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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 / 218 (0.00%)

0 / 92 (0.00%)

1 / 989 (0.10%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pneumonia viral

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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 / 218 (0.00%)

0 / 92 (0.00%)

1 / 989 (0.10%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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 / 218 (0.00%)

0 / 92 (0.00%)

1 / 989 (0.10%)

occurrences causally related to treatment / all

0 / 0

0 / 1

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 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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 / 218 (0.00%)

0 / 92 (0.00%)

1 / 989 (0.10%)

occurrences causally related to treatment / all

0 / 0

0 / 1

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 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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 / 218 (0.00%)

0 / 92 (0.00%)

1 / 989 (0.10%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hyperglycaemia

subjects affected / exposed

0 / 2 (0.00%)

0 / 113 (0.00%)

0 / 13 (0.00%)

0 / 17 (0.00%)

0 / 13 (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 / 218 (0.00%)

0 / 92 (0.00%)

1 / 989 (0.10%)

occurrences causally related to treatment / all

0 / 0

0 / 1

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	SSB: Group 1b: 2 prior doses of BNT162b2 (Second Vaccination)	SSB: Group 1a: 2 prior doses of BNT162b2 (Second Vaccination)	SSB: Group 1b: 2 prior doses of BNT162b2 (First Vaccination)	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 2b: 3 prior doses of BNT162b2	SSB: Group 2a: 3 prior doses of BNT162b2‌	SSB: Group 3b: 3 prior doses of BNT162b2
Total subjects affected by non serious adverse events
subjects affected / exposed	1 / 2 (50.00%)	88 / 113 (77.88%)	5 / 13 (38.46%)	11 / 17 (64.71%)	7 / 13 (53.85%)	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%)	130 / 218 (59.63%)	48 / 92 (52.17%)	532 / 989 (53.79%)
Injury, poisoning and procedural complications
Animal bite
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Arthropod bite
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Skin abrasion
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	1 / 92 (1.09%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Contusion
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Nervous system disorders
Headache (HEADACHE)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	28 / 113 (24.78%)	0 / 13 (0.00%)	0 / 17 (0.00%)	1 / 13 (7.69%)	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%)	9 / 218 (4.13%)	0 / 92 (0.00%)	43 / 989 (4.35%)
occurrences all number	0	28	0	0	1	7	0	0	4	1	0	0	9	0	43
Somnolence (DROWSINESS)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	2 / 17 (11.76%)	0 / 13 (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 / 218 (0.00%)	18 / 92 (19.57%)	0 / 989 (0.00%)
occurrences all number	0	0	0	2	0	0	5	5	0	0	7	11	0	18	0
Somnolence
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	1 / 17 (5.88%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	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%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	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%)	10 / 218 (4.59%)	0 / 92 (0.00%)	24 / 989 (2.43%)
occurrences all number	0	10	0	0	0	2	0	0	4	1	0	0	10	0	24
Fatigue (FATIGUE)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	45 / 113 (39.82%)	3 / 13 (23.08%)	0 / 17 (0.00%)	4 / 13 (30.77%)	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%)	68 / 218 (31.19%)	0 / 92 (0.00%)	283 / 989 (28.61%)
occurrences all number	0	45	3	0	4	11	0	0	13	11	0	0	68	0	283
Injection site pain (PAIN)
alternative assessment type: Systematic
subjects affected / exposed	1 / 2 (50.00%)	71 / 113 (62.83%)	1 / 13 (7.69%)	0 / 17 (0.00%)	4 / 13 (30.77%)	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%)	0 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	1	71	1	0	4	13	1	3	10	8	0	0	0	0	0
Injection site haemorrhage
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Injection site erythema (REDNESS)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	8 / 113 (7.08%)	0 / 13 (0.00%)	2 / 17 (11.76%)	1 / 13 (7.69%)	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%)	14 / 218 (6.42%)	7 / 92 (7.61%)	100 / 989 (10.11%)
occurrences all number	0	8	0	2	1	2	4	4	2	1	1	4	14	7	100
Injection site swelling
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	5 / 113 (4.42%)	0 / 13 (0.00%)	1 / 17 (5.88%)	1 / 13 (7.69%)	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%)	9 / 218 (4.13%)	5 / 92 (5.43%)	39 / 989 (3.94%)
occurrences all number	0	5	0	1	1	2	0	0	2	0	0	1	9	5	39
Pyrexia (FEVER)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	5 / 113 (4.42%)	0 / 13 (0.00%)	2 / 17 (11.76%)	0 / 13 (0.00%)	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%)	15 / 218 (6.88%)	8 / 92 (8.70%)	51 / 989 (5.16%)
occurrences all number	0	5	0	2	0	2	3	1	8	3	0	7	15	8	51
Pyrexia
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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%)	3 / 218 (1.38%)	1 / 92 (1.09%)	8 / 989 (0.81%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	1	2	3	2	8
Injection site pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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%)	1 / 218 (0.46%)	1 / 92 (1.09%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Fatigue
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	1 / 13 (7.69%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	1 / 92 (1.09%)	2 / 989 (0.20%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	1	0	1	2
Injection site erythema
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Chills
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Injection site pain (TENDERNESS)
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	10 / 92 (10.87%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	8	0	10	0
Gastrointestinal disorders
Diarrhea (DIARRHEA)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	4 / 113 (3.54%)	1 / 13 (7.69%)	0 / 17 (0.00%)	0 / 13 (0.00%)	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%)	11 / 218 (5.05%)	0 / 92 (0.00%)	68 / 989 (6.88%)
occurrences all number	0	4	1	0	0	0	0	0	2	1	0	0	11	0	68
Vomiting (VOMITING)
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	4 / 113 (3.54%)	1 / 13 (7.69%)	0 / 17 (0.00%)	1 / 13 (7.69%)	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%)	11 / 218 (5.05%)	0 / 92 (0.00%)	47 / 989 (4.75%)
occurrences all number	0	4	1	0	1	0	0	0	3	2	0	0	11	0	47
Vomiting
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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%)	1 / 218 (0.46%)	2 / 92 (2.17%)	7 / 989 (0.71%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	3	1	2	7
Diarrhoea
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	2 / 92 (2.17%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	2 / 989 (0.20%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	2
Nasal congestion
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	1 / 989 (0.10%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1
Tachypnoea
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Erythema
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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%)	1 / 218 (0.46%)	1 / 92 (1.09%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	1	1	0
Rash maculo-papular
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Irritability
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	9 / 17 (52.94%)	0 / 13 (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 / 218 (0.00%)	32 / 92 (34.78%)	0 / 989 (0.00%)
occurrences all number	0	0	0	9	0	0	8	14	0	0	11	29	0	32	0
Musculoskeletal and connective tissue disorders
Arthralgia
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	10 / 113 (8.85%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	10	0	0	0	2	0	0	0	0	0	0	0	0	0
Myalgia
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	15 / 113 (13.27%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (0.00%)	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%)	7 / 218 (3.21%)	0 / 92 (0.00%)	20 / 989 (2.02%)
occurrences all number	0	15	0	0	0	4	0	0	3	2	0	0	7	0	20
Pain in extremity
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	1 / 17 (5.88%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Infections and infestations
Upper respiratory tract infections
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Otitis media
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	3 / 989 (0.30%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	1	0	0	3
Gastroenteritis
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	1 / 92 (1.09%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Ear infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	1 / 92 (1.09%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Impetigo
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	1 / 92 (1.09%)	0 / 989 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Pharyngitis streptococcal
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	0 / 17 (0.00%)	0 / 13 (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 / 218 (0.00%)	0 / 92 (0.00%)	2 / 989 (0.20%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	2
Metabolism and nutrition disorders
Decreased appetite
alternative assessment type: Systematic
subjects affected / exposed	0 / 2 (0.00%)	0 / 113 (0.00%)	0 / 13 (0.00%)	3 / 17 (17.65%)	0 / 13 (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 / 218 (0.00%)	18 / 92 (19.57%)	0 / 989 (0.00%)
occurrences all number	0	0	0	3	0	0	4	3	0	0	4	13	0	18	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.

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.

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 candidates(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 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 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 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 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 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 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 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: 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: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 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: 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: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: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: 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: 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)

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: 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

Clinical Trial Results:
A master phase 1/2/3 protocol to investigate the safety, tolerability, and immunogenicity of variant- adapted BNT162b2 RNA-based vaccine candidates(s) in healthy children