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Clinical Trial Results:
An Interventional, Randomized, Active-Controlled, Phase 1/2/3 Study to Investigate the Safety, Tolerability, and Immunogenicity of BNT162b RNA-Based Vaccine Candidates in COVID-19 Vaccine-Experienced Healthy Individuals

Summary
EudraCT number	2022-002008-19
Trial protocol	Outside EU/EEA
Global end of trial date	26 Mar 2024

Results information
Results version number	v1(current)
This version publication date	12 Oct 2024
First version publication date	12 Oct 2024
Other versions

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

C4591044

ISRCTN number

US NCT number

NCT05472038

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 clinical trials patient information, BioNTech SE, +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

Final

Date of interim/final analysis

22 Apr 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

26 Mar 2024

Was the trial ended prematurely?

Main objective of the trial

To investigate safety, tolerability, and immunogenicity of BNT162b RNA-based vaccine candidates in COVID-19 vaccine–experienced healthy individuals. These candidates included: 1. Cohort 2 and Cohort 3: Omicron BA.4/BA.5 variant-adapted BNT162b2. - BNT162b2 Bivalent (WT/OMI BA.4/BA.5) in participants 12 years and older. Participants 18 and older received either 30 mcg or 60 mcg dose. Some immunogenicity analyses compared to historic study of BNT162b2 30 mcg, or BNT162b2 Bivalent (WT/OMI BA.1) 30 mcg or 60 mcg. 2. Cohort 1 and Cohort 4: BNT162b5, BNT162b6, BNT162b7, containing modified versions of mRNA segments of the spike protein in adults 18 through 55 years of age. - Cohort 1: BNT162b5 Bivalent (WT/OMI BA.2) with BNT162b2 Bivalent (WT/OMI BA.1) as a comparison. - Cohort 4: BNT162b5 Bivalent (WT/OMI BA.4/BA.5), BNT162b6 Bivalent (WT/OMI BA.4/BA.5), BNT162b7 Bivalent (WT/OMI BA.4/BA.5), BNT162b7 Monovalent (OMI BA.4/BA.5) with BNT162b2 Bivalent (WT/OMI BA.4/BA.5) as a comparison.

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

26 Jul 2022

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

6 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 1451

Worldwide total number of subjects

1451

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)

Children (2-11 years)

Adolescents (12-17 years)

107

Adults (18-64 years)

1144

From 65 to 84 years

197

85 years and over

Subject disposition

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Recruitment details

Screening details

Where appropriate, and as per planned analyses, data is summarised and combined for Cohort 2 (C2) and Cohort 3 (C3) 30 micrograms (mcg) groups (G) per age category to provide sufficient power for the immunogenicity hypotheses for each of the age groups.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Blinding implementation details

Cohort 3 and Cohort 2 (participants 12 through 17 years of age) were open label.

Are arms mutually exclusive

Yes

Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)

Arm description

Participants aged 18-55 years received BNT162b5 Bivalent (wild type [WT]/omicron [OMI] BA.2) 30 mcg intramuscularly at Visit 1 (Day 1).

Arm type

Experimental

Investigational medicinal product name

BNT162b5 Bivalent (WT/OMI BA.2)

Investigational medicinal product code

PF-07302048

Other name

BNT162b5 RNA-LNP vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

BNT162b5 Bivalent (WT/OMI BA.2) 30 mcg intramuscularly at Visit 1.

Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)

Arm description

Participants aged 18-55 years received BNT162b2 Bivalent (WT/OMI BA.1) 30 mcg intramuscularly at Visit 1 (Day 1).

Arm type

Experimental

Investigational medicinal product name

BNT162b2 Bivalent (WT/OMI BA.1)

Investigational medicinal product code

PF-07302048

Other name

BNT162b2 RNA-LNP vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

BNT162b2 Bivalent (WT/OMI BA.1) 30 mcg intramuscularly at Visit 1.

C2 G1:12-17 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)

Arm description

Participants aged 12-17 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Arm type

Experimental

Investigational medicinal product name

BNT162b2 Bivalent (WT/OMI BA.4/BA.5)

Investigational medicinal product code

PF-07302048

Other name

BNT162b2 RNA-LNP vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1.

C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)

Arm description

Participants aged 18-55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Arm type

Experimental

Investigational medicinal product name

BNT162b2 Bivalent (WT/OMI BA.4/BA.5)

Investigational medicinal product code

PF-07302048

Other name

BNT162b2 RNA-LNP vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1.

C2G3: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60mcg)

Arm description

Participants aged 18-55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 60 mcg intramuscularly at Visit 1 (Day 1).

Arm type

Experimental

Investigational medicinal product name

BNT162b2 Bivalent (WT/OMI BA.4/BA.5)

Investigational medicinal product code

PF-07302048

Other name

BNT162b2 RNA-LNP vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 60 mcg intramuscularly at Visit 1.

C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)

Arm description

Participants aged more than (>) 55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Arm type

Experimental

Investigational medicinal product name

BNT162b2 Bivalent (WT/OMI BA.4/BA.5)

Investigational medicinal product code

PF-07302048

Other name

BNT162b2 RNA-LNP vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1.

C2 G5: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60 mcg)

Arm description

Participants aged >55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 60 mcg intramuscularly at Visit 1 (Day 1).

Arm type

Experimental

Investigational medicinal product name

BNT162b2 Bivalent (WT/OMI BA.4/BA.5)

Investigational medicinal product code

PF-07302048

Other name

BNT162b2 RNA-LNP vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 60 mcg intramuscularly at Visit 1.

C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Arm description

Participants aged 18-55 years received BNT162b2 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Arm type

Active comparator

Investigational medicinal product name

BNT162b2 Bivalent (Original/OMI BA.4/BA.5)

Investigational medicinal product code

PF-07302048

Other name

BNT162b2 RNA-LNP vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

BNT162b2 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1.

C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Arm description

Participants aged 18-55 years received BNT162b5 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Arm type

Experimental

Investigational medicinal product name

BNT162b5 Bivalent (Original/OMI BA.4/BA.5)

Investigational medicinal product code

PF-07302048

Other name

BNT162b5 RNA-LNP vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

BNT162b5 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1.

C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Arm description

Participants aged 18-55 years received BNT162b6 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Arm type

Experimental

Investigational medicinal product name

BNT162b6 Bivalent (Original/OMI BA.4/BA.5)

Investigational medicinal product code

PF-07302048

Other name

BNT162b6 RNA-LNP vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

BNT162b6 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1.

C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Arm description

Participants aged 18-55 years received BNT162b7 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Arm type

Experimental

Investigational medicinal product name

BNT162b7 Bivalent (Original/OMI BA.4/BA.5)

Investigational medicinal product code

PF-07302048

Other name

BNT162b7 RNA-LNP vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

BNT162b7 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1.

C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)

Arm description

Participants aged 18-55 years received BNT162b7 Monovalent (OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Arm type

Experimental

Investigational medicinal product name

BNT162b7 Monovalent (OMI BA.4/BA.5)

Investigational medicinal product code

PF-07302048

Other name

BNT162b7 RNA-LNP vaccine

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

BNT162b7 Monovalent (OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1.

Number of subjects in period 1	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)	C2 G1:12-17 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)	C2G3: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60mcg)	C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)	C2 G5: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60 mcg)	C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)
Started	104	102	107	313	110	306	102	62	62	60	60	63
Completed	102	96	102	298	106	300	101	59	57	58	55	59
Not completed	2	6	5	15	4	6	1	3	5	2	5	4
Adverse event, serious fatal	-	-	-	-	-	1	-	-	-	-	-	-
Consent withdrawn by subject	1	3	1	6	1	3	-	2	3	1	2	2
Physician decision	-	-	-	-	1	-	-	-	-	-	-	-
Adverse event, non-fatal	-	-	1	-	-	-	-	-	-	-	-	-
Lost to follow-up	1	3	3	9	2	2	1	-	1	-	2	1
Protocol deviation	-	-	-	-	-	-	-	1	1	1	1	1

Baseline characteristics

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Reporting group title

Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)

Reporting group description

Participants aged 18-55 years received BNT162b5 Bivalent (wild type [WT]/omicron [OMI] BA.2) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)

Reporting group description

Participants aged 18-55 years received BNT162b2 Bivalent (WT/OMI BA.1) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C2 G1:12-17 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)

Reporting group description

Participants aged 12-17 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C2G3: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60mcg)

Reporting group description

Participants aged 18-55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 60 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged more than (>) 55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C2 G5: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60 mcg)

Reporting group description

Participants aged >55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 60 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b2 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b5 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b6 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b7 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)

Reporting group description

Participants aged 18-55 years received BNT162b7 Monovalent (OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group values	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)	C2 G1:12-17 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)	C2G3: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60mcg)	C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)	C2 G5: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60 mcg)	C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)	Total
Number of subjects	104	102	107	313	110	306	102	62	62	60	60	63	1451
Age categorical
Units: Participants
Adolescents (12-17 years)	0	0	107	0	0	0	0	0	0	0	0	0	107
Adults (18-64 years)	104	102	0	313	110	147	61	62	62	60	60	63	1144
From 65-84 years	0	0	0	0	0	157	40	0	0	0	0	0	197
85 years and over	0	0	0	0	0	2	1	0	0	0	0	0	3
Sex: Female, Male
Units: Participants
Female	52	58	48	201	63	167	55	39	31	40	37	38	829
Male	52	44	59	112	47	139	47	23	31	20	23	25	622
Race
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	3	0	0	0	0	0	0	3
Asian	11	10	3	32	9	8	2	7	10	11	3	7	113
Native Hawaiian or Other Pacific Islander	1	2	0	0	0	1	0	0	0	0	0	0	4
Black or African American	10	15	9	26	11	48	8	4	11	6	3	4	155
White	81	71	91	251	90	243	92	49	40	43	53	52	1156
More than one race	1	4	3	4	0	3	0	2	1	0	0	0	18
Unknown or Not Reported	0	0	1	0	0	0	0	0	0	0	1	0	2
Ethnicity
Units: Subjects
Hispanic or Latino	18	23	7	39	15	37	11	7	10	7	12	13	199
Not Hispanic or Latino	84	79	99	272	94	267	89	55	52	53	48	50	1242
Unknown or Not Reported	2	0	1	2	1	2	2	0	0	0	0	0	10

End points

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Reporting group title

Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)

Reporting group description

Participants aged 18-55 years received BNT162b5 Bivalent (wild type [WT]/omicron [OMI] BA.2) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)

Reporting group description

Participants aged 18-55 years received BNT162b2 Bivalent (WT/OMI BA.1) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C2 G1:12-17 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)

Reporting group description

Participants aged 12-17 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C2G3: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60mcg)

Reporting group description

Participants aged 18-55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 60 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged more than (>) 55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C2 G5: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60 mcg)

Reporting group description

Participants aged >55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 60 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b2 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b5 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b6 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b7 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)

Reporting group description

Participants aged 18-55 years received BNT162b7 Monovalent (OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Subject analysis set title

C2G2: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)

Subject analysis set type

Per protocol

Subject analysis set description

Participants aged 18-55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Subject analysis set title

C2 G4: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg)

Subject analysis set type

Per protocol

Subject analysis set description

Participants aged > 55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Subject analysis set title

C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)

Subject analysis set type

Per protocol

Subject analysis set description

Participants aged 18 to 55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Subject analysis set title

18-55 Years (BNT162b2 Bivalent(WT/OMI BA.1)30mcg):C4591031 SSE

Subject analysis set type

Per protocol

Subject analysis set description

A subset of 100 participants in each age group (18 through 55 years of age, >55 years of age) and dose group (30 mcg, 60 mcg) from C4591031 Substudy E (SSE) expanded cohort who received BNT162b2 Bivalent (WT/OMI BA.1) 30 mcg or 60 mcg as a second booster dose were selected for this objective. The subset selected from C4591031 Substudy E included similar percentage of participants with baseline positive SARS-CoV-2 infection status as the groups in Cohort 2 of this study.

Subject analysis set title

18-55 Years(BNT162b2 Bivalent[WT/OMI BA.1] 60mcg):C4591031 SSE

Subject analysis set type

Per protocol

Subject analysis set description

A subset of 100 participants in each age group (18 through 55 years of age, >55 years of age) and dose group (30 mcg, 60 mcg) from C4591031 Substudy E expanded cohort who received BNT162b2 Bivalent (WT/OMI BA.1) 30 mcg or 60 mcg as a second booster dose were selected for this objective. The subset selected from C4591031 Substudy E included similar percentage of participants with baseline positive SARS-CoV-2 infection status as the groups in Cohort 2 of this study.

Subject analysis set title

>55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30mcg):C4591031 SSE

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

>55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 60mcg):C4591031 SSE

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

BNT162b2 30 mcg: C4591031 Substudy E

Subject analysis set type

Per protocol

Subject analysis set description

BNT162b2 experienced participants >55 years of age in study C4591031 [NCT04955626] received one dose (30 mcg) of BNT162b2 intramuscularly. As planned this group served as immunogenicity control arm and participants are not included in enrollment number of current C4591044 [NCT05472038] study.

Primary: Cohort 1: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination

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End point title

Cohort 1: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination ^[1] ^[2]

End point description

Local reactions recorded by participants in electronic diary (e-diary). Local reactions: redness, swelling, pain at injection site. Redness, swelling graded mild: > 2.0-5.0 cm, moderate: >5.0-10.0 cm, severe: >10.0 cm, grade 4: 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, grade 4: emergency room (ER) visit/hospitalisation. Grade 4 reactions (potentially life threatening) classified by investigator/medically qualified person. Any events recorded on the adverse event (AE) case report form (CRF) that are considered local reactions within 7 days after vaccination were consolidated with e-diary data and included in the reactogenicity report. Safety population: all participants receiving study intervention and obtaining informed consent.

End point type

Primary

End point timeframe

From Day 1 to Day 7 after study vaccination

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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 1 reporting groups only.

End point values	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)
Number of subjects analysed	104	102
Units: Percentage of participants
number (confidence interval 95%)
Redness: Any	5.8 (2.1 to 12.1)	5.9 (2.2 to 12.4)
Redness: Mild	3.8 (1.1 to 9.6)	3.9 (1.1 to 9.7)
Redness: Moderate	1.0 (0.0 to 5.2)	2.0 (0.2 to 6.9)
Redness: Severe	1.0 (0.0 to 5.2)	0 (0.0 to 3.6)
Redness: Grade 4	0 (0.0 to 3.5)	0 (0.0 to 3.6)
Swelling: Any	10.6 (5.4 to 18.1)	10.8 (5.5 to 18.5)
Swelling: Mild	6.7 (2.7 to 13.4)	4.9 (1.6 to 11.1)
Swelling: Moderate	2.9 (0.6 to 8.2)	5.9 (2.2 to 12.4)
Swelling: Severe	1.0 (0.0 to 5.2)	0 (0.0 to 3.6)
Swelling: Grade 4	0 (0.0 to 3.5)	0 (0.0 to 3.6)
Pain at injection site: Any	82.7 (74.0 to 89.4)	81.4 (72.4 to 88.4)
Pain at injection site: Mild	67.3 (57.4 to 76.2)	62.7 (52.6 to 72.1)
Pain at injection site: Moderate	15.4 (9.1 to 23.8)	18.6 (11.6 to 27.6)
Pain at injection site: Severe	0 (0.0 to 3.5)	0 (0.0 to 3.6)
Pain at injection site: Grade 4	0 (0.0 to 3.5)	0 (0.0 to 3.6)

No statistical analyses for this end point

Primary: Cohort 1: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination

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End point title

Cohort 1: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination ^[3] ^[4]

End point description

Systemic events recorded by participants in e-diary. Fever: oral temperature >= 38 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 24 hours (h), moderate: >2 times in 24h, severe: required intravenous (IV) hydration. Diarrhea= mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6/more loose stools in 24h. Except fever, Grade 4= ER visit/hospitalisation. Grade 4 events classified by investigator/medically qualified person. Systemic events reported as AEs in CRF within 7 days after vaccination included. Safety population= participants receiving study intervention and obtaining informed consent.

End point type

Primary

End point timeframe

From Day 1 to Day 7 after study vaccination

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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 1 reporting groups only.

End point values	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)
Number of subjects analysed	104	102
Units: Percentage of participants
number (confidence interval 95%)
Fever: Any	1.9 (0.2 to 6.8)	5.9 (2.2 to 12.4)
Fever: >=38.0 deg C to 38.4 deg C	1.0 (0.0 to 5.2)	2.0 (0.2 to 6.9)
Fever: >38.4 deg C to 38.9 deg C	0 (0.0 to 3.5)	1.0 (0.0 to 5.3)
Fever: >38.9 deg C to 40.0 deg C	1.0 (0.0 to 5.2)	2.9 (0.6 to 8.4)
Fever: >40.0 deg C	0 (0.0 to 3.5)	0 (0.0 to 3.6)
Fatigue: Any	73.1 (63.5 to 81.3)	62.7 (52.6 to 72.1)
Fatigue: Mild	37.5 (28.2 to 47.5)	27.5 (19.1 to 37.2)
Fatigue: Moderate	34.6 (25.6 to 44.6)	34.3 (25.2 to 44.4)
Fatigue: Severe	1.0 (0.0 to 5.2)	1.0 (0.0 to 5.3)
Fatigue: Grade 4	0 (0.0 to 3.5)	0 (0.0 to 3.6)
Headache: Any	52.9 (42.8 to 62.8)	46.1 (36.2 to 56.2)
Headache: Mild	29.8 (21.2 to 39.6)	22.5 (14.9 to 31.9)
Headache: Moderate	21.2 (13.8 to 30.3)	22.5 (14.9 to 31.9)
Headache: Severe	1.9 (0.2 to 6.8)	1.0 (0.0 to 5.3)
Headache: Grade 4	0 (0.0 to 3.5)	0 (0.0 to 3.6)
Chills: Any	21.2 (13.8 to 30.3)	19.6 (12.4 to 28.6)
Chills: Mild	10.6 (5.4 to 18.1)	7.8 (3.4 to 14.9)
Chills: Moderate	10.6 (5.4 to 18.1)	11.8 (6.2 to 19.6)
Chills: Severe	0 (0.0 to 3.5)	0 (0.0 to 3.6)
Chills: Grade 4	0 (0.0 to 3.5)	0 (0.0 to 3.6)
Vomiting: Any	1.0 (0.0 to 5.2)	2.0 (0.2 to 6.9)
Vomiting: Mild	1.0 (0.0 to 5.2)	2.0 (0.2 to 6.9)
Vomiting: Moderate	0 (0.0 to 3.5)	0 (0.0 to 3.6)
Vomiting: Severe	0 (0.0 to 3.5)	0 (0.0 to 3.6)
Vomiting: Grade 4	0 (0.0 to 3.5)	0 (0.0 to 3.6)
Diarrhea: Any	14.4 (8.3 to 22.7)	19.6 (12.4 to 28.6)
Diarrhea: Mild	13.5 (7.6 to 21.6)	14.7 (8.5 to 23.1)
Diarrhea: Moderate	1.0 (0.0 to 5.2)	3.9 (1.1 to 9.7)
Diarrhea: Severe0	0 (0.0 to 3.5)	1.0 (0.0 to 5.3)
Diarrhea: Grade 4	0 (0.0 to 3.5)	0 (0.0 to 3.6)
New or worsened muscle pain: Any	35.6 (26.4 to 45.6)	38.2 (28.8 to 48.4)
New or worsened muscle pain: Mild	18.3 (11.4 to 27.1)	23.5 (15.7 to 33.0)
New or worsened muscle pain: Moderate	17.3 (10.6 to 26.0)	14.7 (8.5 to 23.1)
New or worsened muscle pain: Severe	0 (0.0 to 3.5)	0 (0.0 to 3.6)
New or worsened muscle pain: Grade 4	0 (0.0 to 3.5)	0 (0.0 to 3.6)
New or worsened joint pain: Any	18.3 (11.4 to 27.1)	17.6 (10.8 to 26.4)
New or worsened joint pain: Mild	7.7 (3.4 to 14.6)	11.8 (6.2 to 19.6)
New or worsened joint pain: Moderate	10.6 (5.4 to 18.1)	5.9 (2.2 to 12.4)
New or worsened joint pain: Severe	0 (0.0 to 3.5)	0 (0.0 to 3.6)
New or worsened joint pain: Grade 4	0 (0.0 to 3.5)	0 (0.0 to 3.6)

No statistical analyses for this end point

Primary: Cohort 1: Geometric Mean Titer (GMT) of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain Neutralising Titers (NTs) at Baseline- Participants Without Evidence of Infection

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End point title

Cohort 1: Geometric Mean Titer (GMT) of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain Neutralising Titers (NTs) at Baseline- Participants Without Evidence of Infection ^[5] ^[6]

End point description

GMTs and the corresponding 2-sided confidence intervals (CIs) were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on student's t distribution). Evaluable immunogenicity population (EIP) included all eligible randomised/assigned participants who received the study intervention to which they were randomised/assigned, had at least 1 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. Analysis was performed in participants without evidence of infection up to 1 month post study vaccination. Here, ''n’’ signifies participants evaluable for specified rows.

End point type

Primary

End point timeframe

At baseline (before 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 1 reporting groups only.

End point values	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)
Number of subjects analysed	30	29
Units: Titer
geometric mean (confidence interval 95%)
Omicron BA.2 (n=29, 29)	169.3 (96.7 to 296.3)	377.8 (229.2 to 622.8)
Omicron BA.1 (n=30, 29)	103.3 (60.4 to 176.6)	209.5 (147.2 to 298.2)
Reference strain (n=30, 29)	892.0 (526.5 to 1511.3)	1544.2 (993.8 to 2399.4)

No statistical analyses for this end point

Primary: Cohort 1: Percentage of Participants With Adverse Events (AEs) From Study Vaccination Through 1 Month After Study Vaccination

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End point title

Cohort 1: Percentage of Participants With Adverse Events (AEs) From Study Vaccination Through 1 Month After Study Vaccination ^[7] ^[8]

End point description

An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Results excluded local reactions and systemic events data. Safety population included all participants who received the study intervention and where appropriate informed consent was obtained.

End point type

Primary

End point timeframe

From study vaccination on Day 1 through 1 month after study vaccination

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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 1 reporting groups only.

End point values	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)
Number of subjects analysed	104	102
Units: Percentage of participants
number (confidence interval 95%)	8.7 (4.0 to 15.8)	12.7 (7.0 to 20.8)

No statistical analyses for this end point

Primary: Cohort 1: Percentage of Participants With Serious Adverse Events (SAEs) From Study Vaccination Through 6 Months After Study Vaccination

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End point title

Cohort 1: Percentage of Participants With Serious Adverse Events (SAEs) From Study Vaccination Through 6 Months After Study Vaccination ^[9] ^[10]

End point description

An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was an AE that 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 the study intervention and where appropriate informed consent was obtained.

End point type

Primary

End point timeframe

From study vaccination on Day 1 through 6 months after study vaccination

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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 1 reporting groups only.

End point values	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)
Number of subjects analysed	104	102
Units: Percentage of participants
number (confidence interval 95%)	1.0 (0.0 to 5.2)	2.0 (0.2 to 6.9)

No statistical analyses for this end point

Primary: Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at Baseline- Participants With or Without Evidence of Infection

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End point title

Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at Baseline- Participants With or Without Evidence of Infection ^[11] ^[12]

End point description

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). Evaluable immunogenicity population included all eligible randomised/assigned participants who received the study intervention to which they were randomised/assigned, had at least 1 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. Analysis was performed in participants with or without evidence of infection up to 1 month post study vaccination. Here, ''n’’ signifies participants evaluable for specified rows.

End point type

Primary

End point timeframe

At baseline (before study vaccination)

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 1 reporting groups only.

End point values	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)
Number of subjects analysed	103	98
Units: Titer
geometric mean (confidence interval 95%)
Omicron BA.2 (n=102, 96)	1269.1 (854.7 to 1884.6)	1527.5 (1061.3 to 2198.6)
Omicron BA.1 (n=103, 98)	652.7 (448.9 to 949.0)	818.7 (595.9 to 1124.7)
Reference strain (n=103, 98)	3469.8 (2536.5 to 4746.7)	3755.9 (2896.8 to 4869.9)

No statistical analyses for this end point

Primary: Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at 1 Month- Participants Without Evidence of Infection

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End point title

Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at 1 Month- Participants Without Evidence of Infection ^[13] ^[14]

End point description

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). Evaluable immunogenicity population included all eligible randomised/assigned participants who received the study intervention to which they were randomised/assigned, had at least 1 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. Analysis was performed in participants without evidence of infection up to 1 month post study vaccination. Here, ''n’’ signifies participants evaluable for specified rows.

End point type

Primary

End point timeframe

1 month after the study vaccination

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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 1 reporting groups only.

End point values	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)
Number of subjects analysed	30	29
Units: Titer
geometric mean (confidence interval 95%)
Omicron BA.2 (n=30, 28)	2414.8 (1508.5 to 3865.4)	2768.5 (1948.5 to 3933.7)
Omicron BA.1 (n=30, 29)	1666.1 (1085.8 to 2556.6)	1993.8 (1309.1 to 3036.6)
Reference strain (n=30, 29)	8268.9 (5901.9 to 11585.1)	7391.6 (5117.5 to 10676.2)

No statistical analyses for this end point

Primary: Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at 1 Month- Participants With or Without Evidence of Infection

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End point title

Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at 1 Month- Participants With or Without Evidence of Infection ^[15] ^[16]

End point description

End point type

Primary

End point timeframe

1 month after the study vaccination

Notes
[15] - 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 1 reporting groups only.

End point values	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)
Number of subjects analysed	103	98
Units: Titer
geometric mean (confidence interval 95%)
Omicron BA.2 (n=102, 95)	6267.9 (4766.0 to 8243.1)	4984.2 (3976.4 to 6247.4)
Omicron BA.1 (n=103, 98)	3582.2 (2813.7 to 4560.7)	3571.8 (2899.6 to 4399.8)
Reference strain (n=103, 98)	14342.3 (11811.9 to 17414.9)	11246.8 (9395.1 to 13463.6)

No statistical analyses for this end point

Primary: Cohort 1: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants Without Evidence of Infection

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End point title

Cohort 1: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants Without Evidence of Infection ^[17] ^[18]

End point description

GMFR from before study vaccination to 1 month after study vaccination for each strain-specific neutralising titer was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating mean logarithm of fold rises and corresponding CIs (based on student-t distribution). Assay results below lower limit of quantitation (LLOQ) were set to 0.5*LLOQ in analysis. EIP included all eligible randomised/assigned participants who received study intervention to which they were randomised/assigned, had at least 1 valid and determinate immunogenicity result from blood sample collected within 28-42 days after study vaccination, and had no other important protocol deviations as determined by clinician. Analysis was performed in participants without evidence of infection up to 1 month post study vaccination. Here, ''n’’ signifies participants evaluable for specified rows.

End point type

Primary

End point timeframe

From before the study vaccination to 1 month after the 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 1 reporting groups only.

End point values	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)
Number of subjects analysed	30	29
Units: Fold rise
geometric mean (confidence interval 95%)
Omicron BA.2 (n= 29, 28)	14.6 (8.4 to 25.5)	6.9 (4.4 to 10.9)
Omicron BA.1 (n= 30, 29)	16.1 (10.9 to 23.9)	9.5 (6.5 to 13.8)
Reference strain (n= 30, 29)	9.3 (5.9 to 14.6)	4.8 (3.1 to 7.3)

No statistical analyses for this end point

Primary: Cohort 1: GMFR of SARS-CoV-2 Omicron Strain (BA.1 and BA2) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants With or Without Evidence of Infection

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End point title

Cohort 1: GMFR of SARS-CoV-2 Omicron Strain (BA.1 and BA2) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants With or Without Evidence of Infection ^[19] ^[20]

End point description

GMFR from before study vaccination to 1 month after study vaccination for each strain-specific neutralising titer was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating mean logarithm of fold rises and corresponding CIs (based on student-t distribution). Assay results below LLOQ were set to 0.5*LLOQ in analysis. EIP included all eligible randomised/assigned participants who received study intervention to which they were randomised/assigned, had at least 1 valid and determinate immunogenicity result from blood sample collected within 28-42 days after study vaccination, and had no other important protocol deviations as determined by clinician. Analysis was performed in participants with or without evidence of infection up to 1 month post study vaccination. Here, ''n’’ signifies participants evaluable for specified rows.

End point type

Primary

End point timeframe

From before the study vaccination to 1 month after the 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 1 reporting groups only.

End point values	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)
Number of subjects analysed	103	98
Units: Fold rise
geometric mean (confidence interval 95%)
Omicron BA.2 (n=101, 93)	5.0 (3.6 to 6.8)	3.2 (2.3 to 4.3)
Omicron BA.1 (n=103, 98)	5.5 (4.3 to 7.1)	4.4 (3.4 to 5.6)
Reference strain (n=103, 98)	4.1 (3.3 to 5.2)	3.0 (2.4 to 3.7)

No statistical analyses for this end point

Primary: Cohort 1: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain– NTs at 1 Month After Study Vaccination- Participants Without Evidence of Infection

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End point title

Cohort 1: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain– NTs at 1 Month After Study Vaccination- Participants Without Evidence of Infection ^[21] ^[22]

End point description

Seroresponse was defined as achieving >= 4-fold rise in NTs from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, the postvaccination measure of >= 4*LLOQ was considered a seroresponse. EIP included all eligible randomised/assigned participants who received study intervention to which they were randomised/assigned, had at least 1 valid and determinate immunogenicity result from blood sample collected within 28-42 days after study vaccination, and had no other important protocol deviations as determined by clinician. Analysis was performed in participants without evidence of infection up to 1 month post study vaccination. Here, ''n’’ signifies participants evaluable for specified rows.

End point type

Primary

End point timeframe

1 month after the 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 1 reporting groups only.

End point values	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)
Number of subjects analysed	30	29
Units: Percentage of participants
number (confidence interval 95%)
Omicron BA.2 (n=29, 28)	82.8 (64.2 to 94.2)	71.4 (51.3 to 86.8)
Omicron BA.1 (n=30, 29)	93.3 (77.9 to 99.2)	86.2 (68.3 to 96.1)
Reference (n=30, 29)	73.3 (54.1 to 87.7)	51.7 (32.5 to 70.6)

No statistical analyses for this end point

Primary: Cohort 1: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain– NTs at 1 Month After Study Vaccination- Participants With or Without Evidence of Infection

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End point title

End point description

Seroresponse was defined as achieving >= 4-fold rise in NTs from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, the postvaccination measure of >= 4*LLOQ was considered a seroresponse. EIP included all eligible randomised/assigned participants who received study intervention to which they were randomised/assigned, had at least 1 valid and determinate immunogenicity result from blood sample collected within 28-42 days after study vaccination, and had no other important protocol deviations as determined by clinician. Analysis was performed in participants with or without evidence of infection up to 1 month post study vaccination. Here, ''n’’ signifies participants evaluable for specified rows.

End point type

Primary

End point timeframe

1 month after the 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 1 reporting groups only.

End point values	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)
Number of subjects analysed	103	98
Units: Percentage of participants
number (confidence interval 95%)
Omicron BA.2 (n=101, 93)	53.5 (43.3 to 63.5)	40.9 (30.8 to 51.5)
Omicron BA.1 (n=103, 98)	58.3 (48.1 to 67.9)	49.0 (38.7 to 59.3)
Reference strain (n=103, 98)	43.7 (33.9 to 53.8)	30.6 (21.7 to 40.7)

No statistical analyses for this end point

Primary: Cohort 2: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination

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End point title

Cohort 2: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination ^[25] ^[26]

End point description

Local reactions recorded by participants in e-diary. Local reactions: redness, swelling, pain at injection (inj) site. Redness, swelling graded mild: > 2.0-5.0 cm, moderate: >5.0-10.0 cm, severe: >10.0 cm, grade 4 (potentially life threatening): necrosis/exfoliative dermatitis (redness), necrosis (swelling). Pain at inj site graded mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, grade 4 (potentially life threatening): ER visit/hospitalisation. Grade 4 reactions classified by investigator/medically qualified person. Reactions reported as AEs in CRF within 7 days after study vaccination reported. Safety population: all participants receiving study intervention and obtaining informed consent. "Number of Participants Analysed"=participants evaluable for endpoint; “n''=participants evaluable for specified rows.

End point type

Primary

End point timeframe

From Day 1 to Day 7 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2 reporting groups only.

End point values	C2 G1:12-17 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2G3: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60mcg)	C2 G5: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60 mcg)	C2G2: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2 G4: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg)
Number of subjects analysed	107	110	102	102	105
Units: Percentage of participants
number (confidence interval 95%)
Redness: Any (n=107,110,101,102,105)	5.6 (2.1 to 11.8)	10.9 (5.8 to 18.3)	6.9 (2.8 to 13.8)	5.9 (2.2 to 12.4)	2.9 (0.6 to 8.1)
Redness: Mild (n=107,110,101,102,105)	3.7 (1.0 to 9.3)	5.5 (2.0 to 11.5)	4.0 (1.1 to 9.8)	4.9 (1.6 to 11.1)	1.0 (0.0 to 5.2)
Redness: Moderate (n=107,110,101,102,105)	1.9 (0.2 to 6.6)	4.5 (1.5 to 10.3)	3.0 (0.6 to 8.4)	1.0 (0.0 to 5.3)	1.9 (0.2 to 6.7)
Redness: Severe (n=107,110,101,102,105)	0 (0.0 to 3.4)	0.9 (0.0 to 5.0)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
Redness: Grade 4 (n=107,110,101,102,105)	0 (0.0 to 3.4)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
Swelling: Any (n=107,110,101,102,105)	7.5 (3.3 to 14.2)	15.5 (9.3 to 23.6)	8.9 (4.2 to 16.2)	6.9 (2.8 to 13.6)	1.9 (0.2 to 6.7)
Swelling: Mild (n=107,110,101,102,105)	5.6 (2.1 to 11.8)	6.4 (2.6 to 12.7)	5.0 (1.6 to 11.2)	4.9 (1.6 to 11.1)	1.0 (0.0 to 5.2)
Swelling: Moderate (n=107,110,101,102,105)	1.9 (0.2 to 6.6)	9.1 (4.4 to 16.1)	4.0 (1.1 to 9.8)	2.0 (0.2 to 6.9)	1.0 (0.0 to 5.2)
Swelling: Severe (n=107,110,101,102,105)	0 (0.0 to 3.4)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
Swelling: Grade 4 (n=107,110,101,102,105)	0 (0.0 to 3.4)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
Pain at inj site: Any (n=107,110,102,102,105)	70.1 (60.5 to 78.6)	93.6 (87.3 to 97.4)	70.6 (60.7 to 79.2)	79.4 (70.3 to 86.8)	56.2 (46.2 to 65.9)
Pain at inj site: Mild (n=107,110,102,102,105)	42.1 (32.6 to 52.0)	53.6 (43.9 to 63.2)	52.9 (42.8 to 62.9)	63.7 (53.6 to 73.0)	50.5 (40.5 to 60.4)
Pain at inj site: Moderate (n=107,110,102,102,105)	27.1 (19.0 to 36.6)	40.0 (30.8 to 49.8)	17.6 (10.8 to 26.4)	15.7 (9.2 to 24.2)	5.7 (2.1 to 12.0)
Pain at inj site: Severe (n=107,110,102,102,105)	0.9 (0.0 to 5.1)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
Pain at inj site: Grade 4 (n=107,110,102,102,105)	0 (0.0 to 3.4)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)

No statistical analyses for this end point

Primary: Cohort 2: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination

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End point title

Cohort 2: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination ^[27] ^[28]

End point description

Systemic events recorded by participants in e-diary. Fever: oral temperature >= 38 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 24 h, moderate: >2 times in 24h, severe: required IV hydration. Diarrhea= mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6/more loose stools in 24h. Except fever, Grade 4= ER visit/hospitalisation. Grade 4 events classified by investigator/medically qualified person. Systemic events reported as AEs in CRF within 7 days after vaccination included. Safety population= participants receiving study intervention and obtaining IC. "Number of Participants Analysed" =participants evaluable for endpoint.

End point type

Primary

End point timeframe

From Day 1 to Day 7 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2 reporting groups only.

End point values	C2 G1:12-17 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2G3: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60mcg)	C2 G5: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60 mcg)	C2G2: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2 G4: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg)
Number of subjects analysed	107	110	101	102	105
Units: Percentage of participants
number (confidence interval 95%)
Fever: Any	9.3 (4.6 to 16.5)	11.8 (6.4 to 19.4)	13.9 (7.8 to 22.2)	4.9 (1.6 to 11.1)	7.6 (3.3 to 14.5)
Fever: >=38.0 deg C to 38.4 deg C	6.5 (2.7 to 13.0)	7.3 (3.2 to 13.8)	7.9 (3.5 to 15.0)	2.0 (0.2 to 6.9)	5.7 (2.1 to 12.0)
Fever: >38.4 deg C to 38.9 deg C	1.9 (0.2 to 6.6)	2.7 (0.6 to 7.8)	4.0 (1.1 to 9.8)	2.9 (0.6 to 8.4)	1.9 (0.2 to 6.7)
Fever: >38.9 deg C to 40.0 deg C	0.9 (0.0 to 5.1)	1.8 (0.2 to 6.4)	2.0 (0.2 to 7.0)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
Fever: >40.0 deg C	0 (0.0 to 3.4)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
Fatigue: Any	67.3 (57.5 to 76.0)	69.1 (59.6 to 77.6)	53.5 (43.3 to 63.5)	62.7 (52.6 to 72.1)	39.0 (29.7 to 49.1)
Fatigue: Mild	25.2 (17.3 to 34.6)	24.5 (16.8 to 33.7)	23.8 (15.9 to 33.3)	30.4 (21.7 to 40.3)	20.0 (12.8 to 28.9)
Fatigue: Moderate	42.1 (32.6 to 52.0)	43.6 (34.2 to 53.4)	25.7 (17.6 to 35.4)	30.4 (21.7 to 40.3)	18.1 (11.3 to 26.8)
Fatigue: Severe	0 (0.0 to 3.4)	0.9 (0.0 to 5.0)	4.0 (1.1 to 9.8)	2.0 (0.2 to 6.9)	1.0 (0.0 to 5.2)
Fatigue: Grade 4	0 (0.0 to 3.4)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
Headache: Any	50.5 (40.6 to 60.3)	45.5 (35.9 to 55.2)	35.6 (26.4 to 45.8)	44.1 (34.3 to 54.3)	29.5 (21.0 to 39.2)
Headache: Mild	26.2 (18.1 to 35.6)	27.3 (19.2 to 36.6)	20.8 (13.4 to 30.0)	32.4 (23.4 to 42.3)	21.9 (14.4 to 31.0)
Headache: Moderate	24.3 (16.5 to 33.5)	17.3 (10.7 to 25.7)	13.9 (7.8 to 22.2)	11.8 (6.2 to 19.6)	7.6 (3.3 to 14.5)
Headache: Severe	0 (0.0 to 3.4)	0.9 (0.0 to 5.0)	1.0 (0.0 to 5.4)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
Headache: Grade 4	0 (0.0 to 3.4)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
Chills: Any	23.4 (15.7 to 32.5)	27.3 (19.2 to 36.6)	22.8 (15.0 to 32.2)	14.7 (8.5 to 23.1)	12.4 (6.8 to 20.2)
Chills: Mild	17.8 (11.0 to 26.3)	17.3 (10.7 to 25.7)	11.9 (6.3 to 19.8)	8.8 (4.1 to 16.1)	6.7 (2.7 to 13.3)
Chills: Moderate	5.6 (2.1 to 11.8)	9.1 (4.4 to 16.1)	10.9 (5.6 to 18.7)	5.9 (2.2 to 12.4)	5.7 (2.1 to 12.0)
Chills: Severe	0 (0.0 to 3.4)	0.9 (0.0 to 5.0)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
Chills: Grade 4	0 (0.0 to 3.4)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
Vomiting: Any	2.8 (0.6 to 8.0)	1.8 (0.2 to 6.4)	3.0 (0.6 to 8.4)	2.0 (0.2 to 6.9)	1.0 (0.0 to 5.2)
Vomiting: Mild	2.8 (0.6 to 8.0)	0.9 (0.0 to 5.0)	2.0 (0.2 to 7.0)	1.0 (0.0 to 5.3)	1.0 (0.0 to 5.2)
Vomiting: Moderate	0 (0.0 to 3.4)	0.9 (0.0 to 5.0)	1.0 (0.0 to 5.4)	1.0 (0.0 to 5.3)	0 (0.0 to 3.5)
Vomiting: Severe	0 (0.0 to 3.4)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
Vomiting: Grade 4	0 (0.0 to 3.4)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
Diarrhea: Any	6.5 (2.7 to 13.0)	12.7 (7.1 to 20.4)	6.9 (2.8 to 13.8)	13.7 (7.7 to 22.0)	8.6 (4.0 to 15.6)
Diarrhea: Mild	6.5 (2.7 to 13.0)	11.8 (6.4 to 19.4)	5.9 (2.2 to 12.5)	9.8 (4.8 to 17.3)	8.6 (4.0 to 15.6)
Diarrhea: Moderate	0 (0.0 to 3.4)	0.9 (0.0 to 5.0)	1.0 (0.0 to 5.4)	2.9 (0.6 to 8.4)	0 (0.0 to 3.5)
Diarrhea: Severe	0 (0.0 to 3.4)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	1.0 (0.0 to 5.3)	0 (0.0 to 3.5)
Diarrhea: Grade 4	0 (0.0 to 3.4)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
New or worsened muscle pain: Any	26.2 (18.1 to 35.6)	41.8 (32.5 to 51.6)	22.8 (15.0 to 32.2)	31.4 (22.5 to 41.3)	20.0 (12.8 to 28.9)
New or worsened muscle pain: Mild	11.2 (5.9 to 18.8)	21.8 (14.5 to 30.7)	12.9 (7.0 to 21.0)	17.6 (10.8 to 26.4)	12.4 (6.8 to 20.2)
New or worsened muscle pain: Moderate	15.0 (8.8 to 23.1)	19.1 (12.2 to 27.7)	8.9 (4.2 to 16.2)	13.7 (7.7 to 22.0)	7.6 (3.3 to 14.5)
New or worsened muscle pain: Severe	0 (0.0 to 3.4)	0.9 (0.0 to 5.0)	1.0 (0.0 to 5.4)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
New or worsened muscle pain: Grade 4	0 (0.0 to 3.4)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
New or worsened joint pain: Any	12.1 (6.6 to 19.9)	24.5 (16.8 to 33.7)	14.9 (8.6 to 23.3)	16.7 (10.0 to 25.3)	11.4 (6.0 to 19.1)
New or worsened joint pain: Mild	8.4 (3.9 to 15.4)	11.8 (6.4 to 19.4)	5.9 (2.2 to 12.5)	9.8 (4.8 to 17.3)	6.7 (2.7 to 13.3)
New or worsened joint pain: Moderate	3.7 (1.0 to 9.3)	11.8 (6.4 to 19.4)	7.9 (3.5 to 15.0)	6.9 (2.8 to 13.6)	4.8 (1.6 to 10.8)
New or worsened joint pain: Severe	0 (0.0 to 3.4)	0.9 (0.0 to 5.0)	1.0 (0.0 to 5.4)	0 (0.0 to 3.6)	0 (0.0 to 3.5)
New or worsened joint pain: Grade 4	0 (0.0 to 3.4)	0 (0.0 to 3.3)	0 (0.0 to 3.6)	0 (0.0 to 3.6)	0 (0.0 to 3.5)

No statistical analyses for this end point

Primary: Cohort 2: Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination

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End point title

Cohort 2: Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination ^[29] ^[30]

End point description

An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Results excluded local reactions and systemic events data. Safety population included all participants who received the study intervention and where appropriate informed consent was obtained.

End point type

Primary

End point timeframe

From study vaccination through 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2 reporting groups only.

End point values	C2 G1:12-17 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2G3: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60mcg)	C2 G5: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60 mcg)	C2G2: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2 G4: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg)
Number of subjects analysed	107	110	102	103	106
Units: Percentage of participants
number (confidence interval 95%)	7.5 (3.3 to 14.2)	8.2 (3.8 to 15.0)	6.9 (2.8 to 13.6)	2.9 (0.6 to 8.3)	3.8 (1.0 to 9.4)

No statistical analyses for this end point

Primary: Cohort 2: Percentage of Participants With SAEs From Study Vaccination Through 6 Months After Study Vaccination

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End point title

Cohort 2: Percentage of Participants With SAEs From Study Vaccination Through 6 Months After Study Vaccination ^[31] ^[32]

End point description

An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was an AE that 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 the study intervention and where appropriate informed consent was obtained.

End point type

Primary

End point timeframe

From study vaccination through 6 months 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2 reporting groups only.

End point values	C2 G1:12-17 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2G3: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60mcg)	C2 G5: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60 mcg)	C2G2: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2 G4: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg)
Number of subjects analysed	107	110	102	103	106
Units: Percentage of participants
number (confidence interval 95%)	0.9 (0.0 to 5.1)	0.9 (0.0 to 5.0)	0 (0.0 to 3.6)	0 (0.0 to 3.5)	3.8 (1.0 to 9.4)

No statistical analyses for this end point

Primary: Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and 2): Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination

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End point title

Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and 2): Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination ^[33] ^[34]

End point description

Local reactions recorded by participants in e-diary. Local reactions: redness, swelling, pain at injection site. Redness, swelling graded mild: >2.0-5.0 cm, moderate: >5.0-10.0 cm, severe: >10.0 cm, grade 4: necrosis/exfoliative dermatitis (redness), necrosis (swelling). Pain at injection site graded mild: did not interfere with activity, moderate: interfered with activity, severe: prevented daily activity, grade 4: ER visit/hospitalisation. Grade 4 reactions (potentially life threatening) classified by investigator/medically qualified person. Reactions reported as AEs in CRF within 7 days after study vaccination included. Safety population: all participants receiving study intervention and obtaining appropriate informed consent. "Number of Participants Analysed"=participants evaluable for the endpoint, ‘’n’’=participants evaluable for specified rows. Endpoint was planned to be analysed in participants combined from C2 G2 + C3 G1 and C2 G4 + C3 G2.

End point type

Primary

End point timeframe

From Day 1 to Day 7 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2+3 reporting groups only.

End point values	C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)	C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)
Number of subjects analysed	310	301
Units: Percentage of participants
number (confidence interval 95%)
Redness: Any (n=309,300)	6.5 (4.0 to 9.8)	4.0 (2.1 to 6.9)
Redness: Mild (n=309,300)	4.9 (2.7 to 7.9)	2.3 (0.9 to 4.7)
Redness: Moderate (n=309,300)	1.6 (0.5 to 3.7)	1.7 (0.5 to 3.8)
Redness: Severe (n=309,300)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
Redness: Grade 4 (n=309,300)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
Swelling: Any (n=309,300)	7.1 (4.5 to 10.6)	2.7 (1.2 to 5.2)
Swelling: Mild (n=309,300)	5.8 (3.5 to 9.1)	1.7 (0.5 to 3.8)
Swelling: Moderate (n=309,300)	1.3 (0.4 to 3.3)	1.0 (0.2 to 2.9)
Swelling: Severe (n=309,300)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
Swelling: Grade 4 (n=309,300)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
Pain at the injection site: Any (n=310,301)	76.1 (71.0 to 80.8)	57.1 (51.3 to 62.8)
Pain at the injection site: Mild (n=310,301)	57.4 (51.7 to 63.0)	48.8 (43.1 to 54.6)
Pain at the injection site: Moderate (n=310,301)	18.7 (14.5 to 23.5)	8.0 (5.2 to 11.6)
Pain at the injection site: Severe (n=310,301)	0 (0.0 to 1.2)	0.3 (0.0 to 1.8)
Pain at the injection site: Grade 4 (n=310,301)	0 (0.0 to 1.2)	0 (0.0 to 1.2)

No statistical analyses for this end point

Primary: Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination

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End point title

Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination ^[35] ^[36]

End point description

Systemic events recorded in e-diary. Fever: oral temperature>=38 degC, categorised:>=38.0-38.4 degC, >38.4-38.9 degC, >38.9-40.0 degC, >40.0 degC. Fatigue, headache, chills, new/worsened muscle pain, new/worsened joint pain: mild (didn’t interfere activity), moderate (some interference in activity), severe (prevented daily routine activity). Vomiting: mild (1-2 times in 24h), moderate (>2 times in 24h), severe (required IV 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, Grade 4= ER visit/hospitalisation. Grade 4 events classified by investigator/medically qualified person. Systemic events reported as AEs in CRF within 7 days post vaccination. Safety population evaluated. "Number of Participants analysed" (N)= participants evaluable for the endpoint, '’n''=participants evaluable for specified rows. Endpoint planned to be analysed in participants combined from C2G2 + C3G1 and C2G4 + C3G2.

End point type

Primary

End point timeframe

From Day 1 to Day 7 after study vaccination

Notes
[35] - 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2 + 3 reporting groups only.

End point values	C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)	C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)
Number of subjects analysed	309	301
Units: Percentage of participants
number (confidence interval 95%)
Fever: Any (n=309,300)	4.9 (2.7 to 7.9)	4.3 (2.3 to 7.3)
Fever: >=38.0 deg C to 38.4 deg C (n=309,300)	2.9 (1.3 to 5.5)	3.3 (1.6 to 6.0)
Fever: >38.4 deg C to 38.9 deg C (n=309,300)	1.9 (0.7 to 4.2)	1.0 (0.2 to 2.9)
Fever: >38.9 deg C to 40.0 deg C (n=309,300)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
Fever: >40.0 deg C (n=309,300)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
Fatigue: Any (n=309,301)	61.2 (55.5 to 66.6)	38.5 (33.0 to 44.3)
Fatigue: Mild (n=309,301)	26.9 (22.0 to 32.2)	18.6 (14.4 to 23.5)
Fatigue: Moderate (n=309,301)	32.4 (27.2 to 37.9)	18.6 (14.4 to 23.5)
Fatigue: Severe (n=309,301)	1.9 (0.7 to 4.2)	1.3 (0.4 to 3.4)
Fatigue: Grade 4 (n=309,301)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
Headache: Any (n=309,300)	46.6 (40.9 to 52.3)	30.7 (25.5 to 36.2)
Headache: Mild (n=309,300)	28.2 (23.2 to 33.5)	20.7 (16.2 to 25.7)
Headache: Moderate (n=309,300)	17.8 (13.7 to 22.5)	10.0 (6.8 to 14.0)
Headache: Severe (n=309,300)	0.6 (0.1 to 2.3)	0 (0.0 to 1.2)
Headache: Grade 4 (n=309,300)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
Chills: Any (n=309,300)	22.0 (17.5 to 27.0)	12.0 (8.5 to 16.2)
Chills: Mild (n=309,300)	12.3 (8.9 to 16.5)	7.0 (4.4 to 10.5)
Chills: Moderate (n=309,300)	9.1 (6.1 to 12.8)	4.7 (2.6 to 7.7)
Chills: Severe (n=309,300)	0.6 (0.1 to 2.3)	0.3 (0.0 to 1.8)
Chills: Grade 4 (n=309,300)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
Vomiting: Any (n=309,300)	1.9 (0.7 to 4.2)	0.7 (0.1 to 2.4)
Vomiting: Mild (n=309,300)	1.6 (0.5 to 3.7)	0.7 (0.1 to 2.4)
Vomiting: Moderate (n=309,300)	0.3 (0.0 to 1.8)	0 (0.0 to 1.2)
Vomiting: Severe (n=309,300)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
Vomiting: Grade 4 (n=309,300)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
Diarrhea: Any (n=309,301)	10.7 (7.5 to 14.7)	9.6 (6.5 to 13.5)
Diarrhea: Mild (n=309,301)	8.7 (5.8 to 12.5)	7.6 (4.9 to 11.2)
Diarrhea: Moderate (n=309,301)	1.6 (0.5 to 3.7)	2.0 (0.7 to 4.3)
Diarrhea: Severe (n=309,301)	0.3 (0.0 to 1.8)	0 (0.0 to 1.2)
Diarrhea: Grade 4 (n=309,301)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
New or worsened muscle pain: Any (n=309,300)	30.4 (25.3 to 35.9)	18.0 (13.8 to 22.8)
New or worsened muscle pain: Mild (n=309,300)	15.2 (11.4 to 19.7)	10.0 (6.8 to 14.0)
New or worsened muscle pain: Moderate (n=309,300)	15.2 (11.4 to 19.7)	8.0 (5.2 to 11.7)
New or worsened muscle pain: Severe (n=309,300)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
New or worsened muscle pain: Grade 4 (n=309,300)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
New or worsened joint pain: Any (n=309,300)	14.9 (11.1 to 19.4)	12.0 (8.5 to 16.2)
New or worsened joint pain: Mild (n=309,300)	6.8 (4.3 to 10.2)	6.7 (4.1 to 10.1)
New or worsened joint pain: Moderate (n=309,300)	8.1 (5.3 to 11.7)	5.3 (3.1 to 8.5)
New or worsened joint pain: Severe (n=309,300)	0 (0.0 to 1.2)	0 (0.0 to 1.2)
New or worsened joint pain: Grade 4 (n=309,300)	0 (0.0 to 1.2)	0 (0.0 to 1.2)

No statistical analyses for this end point

Primary: Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination

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End point title

Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination ^[37] ^[38]

End point description

End point type

Primary

End point timeframe

From study vaccination through 1 month after study vaccination

Notes
[37] - 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2+3 reporting groups only.

End point values	C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)	C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)
Number of subjects analysed	313	306
Units: Percentage of participants
number (confidence interval 95%)	6.1 (3.7 to 9.3)	6.9 (4.3 to 10.3)

No statistical analyses for this end point

Primary: Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants With SAEs From Study Vaccination Through 6 Months After Study Vaccination

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End point title

Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants With SAEs From Study Vaccination Through 6 Months After Study Vaccination ^[39] ^[40]

End point description

An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was an AE that 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 the study intervention and where appropriate informed consent was obtained. The endpoint was planned per protocol to be analysed in participants combined from Cohort 2 Group 2 + Cohort 3 Group 1 and Cohort 2 Group 4 + Cohort 3 Group 2.

End point type

Primary

End point timeframe

From study vaccination through 6 months after study vaccination

Notes
[39] - 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2 + 3 reporting groups only.

End point values	C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)	C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)
Number of subjects analysed	313	306
Units: Percentage of participants
number (confidence interval 95%)	0.6 (0.1 to 2.3)	3.3 (1.6 to 5.9)

No statistical analyses for this end point

Primary: GMR of Omicron (BA.4/BA.5)– NTs of BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg C2 G4/C3 G2 Combined in C4591044 Compared to NT of BNT162b2 30 mcg in C4591031– 1 Month After Vaccination Among Participants >55 Years of Age

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End point title

GMR of Omicron (BA.4/BA.5)– NTs of BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg C2 G4/C3 G2 Combined in C4591044 Compared to NT of BNT162b2 30 mcg in C4591031– 1 Month After Vaccination Among Participants >55 Years of Age ^[41]

End point description

Model based GMT of OMI BA.4/BA.5 NTs induced by BNT162b2 Bivalent 30 mcg groups of C4591044 C2/3 combined and BNT162b2 30 mcg of C4591031 Substudy E in participants >55 years = descriptive data. GMTs and 95% CIs were calculated by exponentiating least square (LS) means and corresponding CI based on analysis of logarithmically transformed NT using linear regression model with terms of baseline NT (log scale) and vaccine group. Assay results below LLOQ=0.5*LLOQ. Model based geometric mean ratio (GMR) = statistical section: OMI BA.4/BA.5 NTs induced 1 month post BNT162b2 Bivalent vaccination in C4591044 to 1 month post BNT162b2 vaccination in C4591031 in participants >55 years. Endpoint was planned to be analysed in participants of C2G4 + C3G2 of C4591044 and BNT162b2 experienced participants of study C4591031 (control arm). Analysis was performed in EIP with or without evidence of infection up to 1 month post study vaccination. "N"=participants evaluable for this endpoint.

End point type

Primary

End point timeframe

1 month after study vaccination

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2 + 3 reporting groups only.

End point values	C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)	BNT162b2 30 mcg: C4591031 Substudy E
Number of subjects analysed	282	273
Units: Titer
geometric mean (confidence interval 95%)	3373.4 (3000.3 to 3793.0)	1160.7 (1030.3 to 1307.7)

C2 (G4)+C3 (G2): >55 Years Vs C4591031 Substudy E

Statistical analysis description

Superiority based on model-based GMR was declared if the lower limit of the 2-sided 95% CI for the model-based GMR was greater than 1.

Comparison groups

C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg) v BNT162b2 30 mcg: C4591031 Substudy E

Number of subjects included in analysis

555

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Model-Based GMR

Point estimate

2.91

Confidence interval

level

95%

sides

2-sided

lower limit

2.45

upper limit

3.44

Primary: Difference in Percentage of Participants With Seroresponse to OMI BA.4/BA.5 for BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg C2 G4/C3 G2 Combined in C4591044 and for BNT162b2 30 mcg in C4591031– 1 Month After Vaccination Among Participants >55 Years of Age

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End point title

Difference in Percentage of Participants With Seroresponse to OMI BA.4/BA.5 for BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg C2 G4/C3 G2 Combined in C4591044 and for BNT162b2 30 mcg in C4591031– 1 Month After Vaccination Among Participants >55 Years of Age ^[42]

End point description

Seroresponse: achieving >= 4-fold rise in NTs from baseline (before study vaccination). If baseline measurement was below LLOQ, postvaccination measure of >= 4*LLOQ was considered seroresponse. Percentage of participants with seroresponse to OMI BA.4/BA.5 for BNT Bivalent 30 mcg in Study C4591044 [NCT05472038] Cohort 2/3 combined and BNT 30 mcg in Study C4591031 [NCT04955626] Substudy E in participants >55 years presented as descriptive data. Adjusted difference in seroresponse rate to OMI BA.4/BA.5 between BNT 30 mcg 1 month after vaccination in study C4591044 and 1 month after BNT vaccination in study C4591031 in participants >55 years reported in statistical section. Endpoint was planned to be analysed in participants from C2 G4 + C3 G2 and BNT experienced participants >55 years from study C4591031 Substudy E (control arm). Analysis was performed in EIP with or without evidence of infection up to 1 month post study vaccination. "N" = participants evaluable for this endpoint.

End point type

Primary

End point timeframe

1 month after study vaccination

Notes
[42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2+3 reporting groups only.

End point values	C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)	BNT162b2 30 mcg: C4591031 Substudy E
Number of subjects analysed	282	273
Units: Percentage of participants
number (confidence interval 95%)	66.7 (60.8 to 72.1)	46.5 (40.5 to 52.6)

C2 (G4)+C3 (G2) Vs C4591031 Sub study E

Statistical analysis description

Adjusted difference and 2-Sided CI based on the Miettinen and Nurminen method stratified by baseline NT category (< median,>= median) for difference in proportions. The median of baseline NT was calculated based on pooled data in 2 comparator groups.

Comparison groups

C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg) v BNT162b2 30 mcg: C4591031 Substudy E

Number of subjects included in analysis

555

Analysis specification

Pre-specified

Analysis type

^[43]

Method

Parameter type

Adjusted Difference in Percentages

Point estimate

26.77

Confidence interval

level

95%

sides

2-sided

lower limit

19.59

upper limit

33.95

Notes
[43] - Noninferiority based on seroresponse was declared if the lower limit of the 2-sided 95% CI for the difference in percentages of participants with seroresponse is >-5%.

Primary: GMR of Omicron (BA.4/BA.5)– NTs of BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg C2 G2/C3 G1 Combined for 18-55 Years Compared to BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg C2 G4/C3 G2 Combined for >55 Years– 1 Month After Vaccination in C4591044

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End point title

GMR of Omicron (BA.4/BA.5)– NTs of BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg C2 G2/C3 G1 Combined for 18-55 Years Compared to BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg C2 G4/C3 G2 Combined for >55 Years– 1 Month After Vaccination in C4591044 ^[44]

End point description

Model based GMT of OMI BA.4/BA.5 NTs induced by BNT Bivalent 30mcg groups of study C4591044 [NCT05472038] Cohort 2/3 combined in participants 18-55 years of age compared to participants >55 years of age are presented as descriptive data. GMTs and 2-sided 95% CIs were calculated by exponentiating LS means and corresponding CIs based on analysis of logarithmically transformed NT using linear regression model with terms of baseline NT (log scale) and vaccine group. Assay results below LLOQ= 0.5*LLOQ. Model based GMR: OMI BA.4/BA.5 NTs induced 1 month after BNT Bivalent vaccination in study C4591044 among participants 18-55 years of age compared to participants >55 years of age is reported in statistical section. Endpoint was planned to be analysed in participants combined from C2 G2 + C3 G1 and C2 G4 + C3 G2. Analysis was performed in EIP with or without evidence of infection up to 1 month post study vaccination. "N"= participants evaluable for this endpoint.

End point type

Primary

End point timeframe

1 month after study vaccination

Notes
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2+3 reporting groups only.

End point values	C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)	C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)
Number of subjects analysed	282	294
Units: Titer
geometric mean (confidence interval 95%)	4344.4 (3850.2 to 4902.1)	4254.2 (3779.6 to 4788.4)

C2(G2)+C3(G1) 18-55 Vs C2(G4)+C3(G2) >55:BNT30mcg

Statistical analysis description

Noninferiority based on model-based GMR was declared if the lower limit of the 2-sided 95% CI for the model-based GMR is greater than 0.67.

Comparison groups

C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg) v C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)

Number of subjects included in analysis

576

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

Model-Based GMR

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.83

upper limit

1.16

Primary: Difference in Percentage of Participants With Seroresponse to OMI BA.4/BA.5 of BNT162b2 30mcg Cohort 2 (Group 2)/ Cohort 3 (Group 1) 18-55 Years of age and Cohort 2 (Group 4)/ Cohort 3 (Group 2) >55 Years of age– 1 Month After Vaccination in C4591044

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End point title

Difference in Percentage of Participants With Seroresponse to OMI BA.4/BA.5 of BNT162b2 30mcg Cohort 2 (Group 2)/ Cohort 3 (Group 1) 18-55 Years of age and Cohort 2 (Group 4)/ Cohort 3 (Group 2) >55 Years of age– 1 Month After Vaccination in C4591044 ^[45]

End point description

Seroresponse: achieving >= 4-fold rise in NTs from baseline (before study vaccination). If baseline measurement was below LLOQ, postvaccination measure of >= 4*LLOQ was considered seroresponse. Percentage of participants with seroresponse to OMI BA.4/BA.5 for BNT162b2 Bivalent 30 mcg in Study C4591044 [NCT05472038] Cohort 2/3 combined in participants 18-55 years of age compared to participants >55 years of age are presented as descriptive data. Adjusted difference in seroresponse rate to OMI BA.4/BA.5 between BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg 1 month after vaccination in study C4591044 in participants 18-55 years of age compared to participants >55 years of age is reported in statistical section. Endpoint was planned to be analysed in participants combined from C2 G2 + C3 G1 and C2 G4 + C3 G2. EIP was analysed with or without evidence of infection up to 1 month post study vaccination. "N"=participants evaluable for this endpoint.

End point type

Primary

End point timeframe

1 month after study vaccination

Notes
[45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2+3 reporting groups only.

End point values	C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)	C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)
Number of subjects analysed	294	282
Units: Percentage of participants
number (confidence interval 95%)	61.2 (55.4 to 66.8)	66.7 (60.8 to 72.1)

C2(G2)+C3(G1) 18-55 Vs C2(G4)+C3(G2) >55:BNT30mcg

Statistical analysis description

Noninferiority based on seroresponse was declared if the lower limit of the 2-sided 95% CI for the difference in percentages of participants with seroresponse is >-10%.

Comparison groups

C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg) v C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)

Number of subjects included in analysis

576

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

Adjusted Difference in Percentages

Point estimate

-3.03

Confidence interval

level

95%

sides

2-sided

lower limit

-9.68

upper limit

3.63

Primary: Cohort 2: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain NTs at Baseline

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End point title

Cohort 2: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain NTs at Baseline ^[46] ^[47]

End point description

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). This endpoint was planned per protocol to be analysed in participants from Cohort 2 and control arms of BNT162b2 Bivalent (WT/OMI BA.1) experienced participants 12-17 years of age, 18-55 years of age and >55 years of age from study C4591031 Substudy E. Analysis was performed in EIP with or without evidence of infection up to 1 month post study vaccination. Here, "Number of Participants Analysed" signifies participants evaluable for this endpoint and ''n’’ signifies participants evaluable for specified rows.

End point type

Primary

End point timeframe

At baseline (before study vaccination)

Notes
[46] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[47] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2 reporting groups only.

End point values	C2 G1:12-17 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2G3: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60mcg)	C2 G5: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60 mcg)	C2G2: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2 G4: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg)	18-55 Years (BNT162b2 Bivalent(WT/OMI BA.1)30mcg):C4591031 SSE	18-55 Years(BNT162b2 Bivalent[WT/OMI BA.1] 60mcg):C4591031 SSE	>55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30mcg):C4591031 SSE	>55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 60mcg):C4591031 SSE
Number of subjects analysed	105	102	98	95	102	100	100	100	100
Units: Titer
geometric mean (confidence interval 95%)
OMI BA.4/BA.5(n=104,102,98,100,100,99,100,101,95)	1105.8 (835.1 to 1464.3)	607.0 (433.2 to 850.6)	582.4 (397.6 to 853.1)	338.3 (238.1 to 480.7)	301.9 (215.6 to 422.8)	151.5 (113.4 to 202.3)	420.6 (312.7 to 565.6)	225.4 (164.1 to 309.6)	249.6 (180.5 to 345.2)
OMI BA.1(n=105,102,96,100,98,100,97,102,95)	1190.5 (921.8 to 1537.5)	653.1 (466.3 to 914.8)	581.2 (392.5 to 860.6)	346.0 (240.0 to 498.9)	365.1 (260.8 to 511.1)	194.6 (142.4 to 266.0)	492.4 (351.5 to 689.9)	316.3 (215.9 to 463.4)	285.6 (195.8 to 416.5)
Reference(n=105,101,98,100,100,100,100,101,95)	6863.3 (5587.8 to 8430.1)	4287.4 (3245.6 to 5663.8)	4324.8 (3099.0 to 6035.4)	2349.0 (1693.4 to 3258.4)	2643.1 (1990.8 to 3509.1)	1338.4 (1056.9 to 1695.1)	3933.2 (3058.0 to 5058.9)	1985.7 (1510.1 to 2611.0)	2509.3 (1906.8 to 3302.3)

No statistical analyses for this end point

Primary: Cohort 2: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain NTs at 1 Month

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End point title

Cohort 2: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain NTs at 1 Month ^[48] ^[49]

End point description

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). This endpoint was planned to be analysed in participants from Cohort 2 and control arms of BNT162b2 experienced participants 12-17 years of age, 18-55 years of age and >55 years of age from study C4591031 substudy E. Analysis was performed in EIP with or without evidence of infection up to 1 month post study vaccination. Here, "Number of Participants Analysed" signifies participants evaluable for this endpoint and ''n’’ signifies participants evaluable for specified rows.

End point type

Primary

End point timeframe

1 month after the study vaccination

Notes
[48] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2 reporting groups only.

End point values	C2 G1:12-17 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2G3: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60mcg)	C2 G5: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60 mcg)	C2G2: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2 G4: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg)	18-55 Years (BNT162b2 Bivalent(WT/OMI BA.1)30mcg):C4591031 SSE	18-55 Years(BNT162b2 Bivalent[WT/OMI BA.1] 60mcg):C4591031 SSE	>55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30mcg):C4591031 SSE	>55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 60mcg):C4591031 SSE
Number of subjects analysed	105	102	99	95	102	100	100	100	100
Units: Titer
geometric mean (confidence interval 95%)
OMI BA.4/BA.5(n=105,102,99,100,100,100,100,102,95)	8212.8 (6807.3 to 9908.7)	5454.2 (4292.2 to 6930.8)	5472.8 (3930.9 to 7619.6)	2839.0 (2150.0 to 3748.8)	3019.8 (2327.5 to 3918.0)	1072.0 (816.1 to 1408.1)	2525.2 (1970.5 to 3236.0)	943.4 (733.4 to 1213.6)	1520.9 (1196.0 to 1934.0)
OMI BA.1(n=105,101,99,100,99,100,100,102,95)	6687.6 (5617.0 to 7962.3)	4112.4 (3263.6 to 5181.9)	4264.0 (3247.9 to 5597.9)	2407.2 (1884.9 to 3074.2)	2656.1 (2089.6 to 3376.3)	1819.0 (1401.6 to 2360.6)	3143.8 (2486.9 to 3974.1)	1617.7 (1274.7 to 2053.0)	1936.9 (1489.4 to 2518.8)
Reference(n=105,102,99,99,100,100,99,102,95)	23641.3 (20473.1 to 27299.8)	18614.7 (15754.1 to 21994.7)	22982.3 (18524.3 to 28513.3)	11919.3 (9839.1 to 14439.3)	12103.8 (9992.0 to 14662.0)	6913.9 (5690.4 to 8400.5)	14685.8 (12301.1 to 17532.8)	7128.6 (5954.4 to 8534.3)	11106.5 (8956.8 to 13772.2)

No statistical analyses for this end point

Primary: Cohort 2: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination

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End point title

Cohort 2: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination ^[50] ^[51]

End point description

GMFR from before the study vaccination to 1 month after the study vaccination for each strain-specific neutralising titer 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. This endpoint was planned to be analysed in participants from Cohort 2 and control arms of BNT162b2 experienced participants 12-17 years of age, 18-55 years of age and >55 years of age from study C4591031 substudy E. Analysis was performed in EIP with or without evidence of infection up to 1 month post study vaccination. Here, "Number of Participants Analysed" signifies participants evaluable for this endpoint and ''n’’ signifies participants evaluable for specified rows.

End point type

Primary

End point timeframe

From before the study vaccination to 1 month after the study vaccination

Notes
[50] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[51] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2 reporting groups only.

End point values	C2 G1:12-17 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2G3: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60mcg)	C2 G5: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60 mcg)	C2G2: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2 G4: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg)	18-55 Years (BNT162b2 Bivalent(WT/OMI BA.1)30mcg):C4591031 SSE	18-55 Years(BNT162b2 Bivalent[WT/OMI BA.1] 60mcg):C4591031 SSE	>55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30mcg):C4591031 SSE	>55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 60mcg):C4591031 SSE
Number of subjects analysed	105	102	98	95	102	100	100	100	100
Units: Fold rise
geometric mean (confidence interval 95%)
OMI BA.4/BA.5(n=104,102,98,100,100,99,100,101,95)	7.6 (6.0 to 9.6)	9.0 (6.9 to 11.8)	9.3 (6.8 to 12.8)	8.4 (6.3 to 11.1)	10.0 (7.5 to 13.3)	7.1 (5.7 to 8.9)	6.0 (4.7 to 7.7)	4.2 (3.4 to 5.2)	6.1 (4.7 to 7.9)
OMI BA.1(n=105,101,96,100,97,100,97,102,95)	5.6 (4.6 to 6.9)	6.3 (4.9 to 8.2)	7.3 (5.4 to 9.7)	7.0 (5.3 to 9.1)	7.3 (5.6 to 9.5)	9.3 (7.3 to 12.0)	6.4 (4.9 to 8.3)	5.1 (3.9 to 6.6)	6.8 (5.1 to 9.1)
Reference(n=105,101,98,99,100,100,99,101,95)	3.4 (2.9 to 4.1)	4.3 (3.4 to 5.5)	5.4 (4.0 to 7.1)	5.1 (3.9 to 6.6)	4.6 (3.7 to 5.8)	5.2 (4.3 to 6.3)	3.7 (3.0 to 4.6)	3.6 (2.9 to 4.4)	4.4 (3.5 to 5.6)

No statistical analyses for this end point

Primary: Cohort 2: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain– NTs at 1 Month After Study Vaccination

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End point title

Cohort 2: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain– NTs at 1 Month After Study Vaccination ^[52] ^[53]

End point description

Seroresponse: achieving >= 4-fold rise in NTs from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, the postvaccination measure of >= 4*LLOQ was considered a seroresponse. Percentage of participants with seroresponse to OMI BA.4/BA.5 for BNT162b2 Bivalent 30 and 60 mcg in Study C4591044 [NCT05472038] Cohort 2 and BNT162b2 30 mcg in Study C4591031 [NCT04955626] Substudy E among participants 12-17 years of age, 18-55 and >55 years of age are presented as descriptive data. This endpoint was planned to be analysed in participants from Cohort 2 and control arms of BNT162b2 experienced participants 18-55 years of age and >55 years of age from study C4591031 substudy E. Analysis was performed in EIP with or without evidence of infection up to 1 month post study vaccination. Here, "Number of Participants Analysed" signifies participants evaluable for this endpoint and ''n’’ signifies participants evaluable for specified rows.

End point type

Primary

End point timeframe

1 month after the study vaccination

Notes
[52] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[53] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2 reporting groups only.

End point values	C2 G1:12-17 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2G3: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60mcg)	C2 G5: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 60 mcg)	C2G2: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg)	C2 G4: >55 Years (BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg)	18-55 Years (BNT162b2 Bivalent(WT/OMI BA.1)30mcg):C4591031 SSE	18-55 Years(BNT162b2 Bivalent[WT/OMI BA.1] 60mcg):C4591031 SSE	>55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30mcg):C4591031 SSE	>55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 60mcg):C4591031 SSE
Number of subjects analysed	105	102	98	95	102	100	100	100	100
Units: Percentage of participants
number (confidence interval 95%)
OMI BA.4/BA.5(n=104,102,98,100,100,99,100,101,95)	66.3 (56.4 to 75.3)	66.7 (56.6 to 75.7)	63.3 (52.9 to 72.8)	64.2 (53.7 to 73.8)	71.3 (61.4 to 79.9)	62.0 (51.7 to 71.5)	59.0 (48.7 to 68.7)	37.4 (27.9 to 47.7)	53.0 (42.8 to 63.1)
OMI BA.1(n=105,101,96,100,97,100,97,102,95)	63.8 (53.9 to 73.0)	60.4 (50.2 to 70.0)	65.6 (55.2 to 75.0)	54.7 (44.2 to 65.0)	63.7 (53.6 to 73.0)	75.0 (65.3 to 83.1)	56.7 (46.3 to 66.7)	52.0 (41.8 to 62.1)	58.8 (48.3 to 68.7)
Reference(n=105,101,98,99,100,100,99,101,95)	41.0 (31.5 to 51.0)	51.5 (41.3 to 61.6)	55.1 (44.7 to 65.2)	49.5 (39.1 to 59.9)	50.5 (40.4 to 60.0)	59.6 (49.3 to 69.3)	41.0 (31.3 to 51.3)	41.0 (31.3 to 51.3)	44.4 (34.5 to 54.8)

No statistical analyses for this end point

Primary: Cohort 4: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination

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End point title

Cohort 4: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination ^[54] ^[55]

End point description

Local reactions were recorded by participants in e-diary. Local reactions: redness, swelling, pain at injection site. Redness and swelling were graded as mild: > 2.0-5.0 cm, moderate: >5.0-10.0 cm, severe: >10.0 cm, grade 4: necrosis or exfoliative dermatitis (redness), necrosis (swelling). Pain at injection site was graded as mild: did not interfere with daily activity, moderate: interfered with daily activity, severe: prevented daily activity, grade 4: ER visit or hospitalisation. Grade 4 reactions (potentially life threatening) were classified by investigator/medically qualified person. Local reactions reported as AEs in CRF within 7 days after study vaccination were reported. Safety population: all participants receiving study intervention and obtaining informed consent. Here, "Number of Participants Analysed"= participants evaluable for this endpoint.

End point type

Primary

End point timeframe

From Day 1 to Day 7 after study vaccination

Notes
[54] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[55] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 4 reporting groups only.

End point values	C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)
Number of subjects analysed	62	61	60	60	63
Units: Percentage of participants
number (confidence interval 95%)
Redness: Any	4.8 (1.0 to 13.5)	3.3 (0.4 to 11.3)	5.0 (1.0 to 13.9)	1.7 (0.0 to 8.9)	1.6 (0.0 to 8.5)
Redness: Mild	3.2 (0.4 to 11.2)	3.3 (0.4 to 11.3)	5.0 (1.0 to 13.9)	1.7 (0.0 to 8.9)	1.6 (0.0 to 8.5)
Redness: Moderate	1.6 (0.0 to 8.7)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Redness: Severe	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Redness: Grade 4	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Swelling: Any	1.6 (0.0 to 8.7)	3.3 (0.4 to 11.3)	6.7 (1.8 to 16.2)	3.3 (0.4 to 11.5)	3.2 (0.4 to 11.0)
Swelling: Mild	0 (0.0 to 5.8)	0 (0.0 to 5.9)	6.7 (1.8 to 16.2)	3.3 (0.4 to 11.5)	3.2 (0.4 to 11.0)
Swelling: Moderate	1.6 (0.0 to 8.7)	3.3 (0.4 to 11.3)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Swelling: Severe	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Swelling: Grade 4	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Pain at injection site: Any	85.5 (74.2 to 93.1)	88.5 (77.8 to 95.3)	76.7 (64.0 to 86.6)	76.7 (64.0 to 86.6)	84.1 (72.7 to 92.1)
Pain at injection site: Mild	64.5 (51.3 to 76.3)	65.6 (52.3 to 77.3)	68.3 (55.0 to 79.7)	61.7 (48.2 to 73.9)	68.3 (55.3 to 79.4)
Pain at injection site: Moderate	21.0 (11.7 to 33.2)	21.3 (11.9 to 33.7)	8.3 (2.8 to 18.4)	15.0 (7.1 to 26.6)	15.9 (7.9 to 27.3)
Pain at injection site: Severe	0 (0.0 to 5.8)	1.6 (0.0 to 8.8)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Pain at injection site: Grade 4	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)

No statistical analyses for this end point

Primary: Cohort 4: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination

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End point title

Cohort 4: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination ^[56] ^[57]

End point description

Systemic events were recorded by participants in e-diary. Fever: oral temperature >= 38 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 or worsened muscle pain and new or worsened joint pain= mild: did not interfere with activity, moderate: some interference with activity, severe: prevented daily routine activity. Vomiting= mild: 1-2 times in 24h, moderate: >2 times in 24h, severe: required IV 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, Grade 4= ER visit or hospitalisation. Grade 4 events were classified by investigator or medically qualified person. Systemic events reported as AEs in CRF within 7 days after vaccination are included. Safety population= participants receiving study intervention and obtaining informed consent. "Number of Participants Analysed"= participants evaluable for this endpoint.

End point type

Primary

End point timeframe

From Day 1 to Day 7 after study vaccination

Notes
[56] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 4 reporting groups only.

End point values	C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)
Number of subjects analysed	62	61	60	60	63
Units: Percentage of participants
number (confidence interval 95%)
Fever: Any	6.5 (1.8 to 15.7)	6.6 (1.8 to 15.9)	10.0 (3.8 to 20.5)	5.0 (1.0 to 13.9)	9.5 (3.6 to 19.6)
Fever: >=38.0 deg C to 38.4 deg C	3.2 (0.4 to 11.2)	6.6 (1.8 to 15.9)	5.0 (1.0 to 13.9)	5.0 (1.0 to 13.9)	4.8 (1.0 to 13.3)
Fever: >38.4 deg C to 38.9 deg C	3.2 (0.4 to 11.2)	0 (0.0 to 5.9)	3.3 (0.4 to 11.5)	0 (0.0 to 6.0)	1.6 (0.0 to 8.5)
Fever: >38.9 deg C to 40.0 deg C	0 (0.0 to 5.8)	0 (0.0 to 5.9)	1.7 (0.0 to 8.9)	0 (0.0 to 6.0)	3.2 (0.4 to 11.0)
Fever: >40.0 deg C	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Fatigue: Any	61.3 (48.1 to 73.4)	63.9 (50.6 to 75.8)	73.3 (60.3 to 83.9)	66.7 (53.3 to 78.3)	54.0 (40.9 to 66.6)
Fatigue: Mild	25.8 (15.5 to 38.5)	29.5 (18.5 to 42.6)	38.3 (26.1 to 51.8)	35.0 (23.1 to 48.4)	17.5 (9.1 to 29.1)
Fatigue: Moderate	35.5 (23.7 to 48.7)	34.4 (22.7 to 47.7)	33.3 (21.7 to 46.7)	30.0 (18.8 to 43.2)	34.9 (23.3 to 48.0)
Fatigue: Severe	0 (0.0 to 5.8)	0 (0.0 to 5.9)	1.7 (0.0 to 8.9)	1.7 (0.0 to 8.9)	1.6 (0.0 to 8.5)
Fatigue: Grade 4	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Headache: Any	59.7 (46.4 to 71.9)	36.1 (24.2 to 49.4)	41.7 (29.1 to 55.1)	46.7 (33.7 to 60.0)	39.7 (27.6 to 52.8)
Headache: Mild	38.7 (26.6 to 51.9)	16.4 (8.2 to 28.1)	23.3 (13.4 to 36.0)	23.3 (13.4 to 36.0)	22.2 (12.7 to 34.5)
Headache: Moderate	17.7 (9.2 to 29.5)	19.7 (10.6 to 31.8)	18.3 (9.5 to 30.4)	21.7 (12.1 to 34.2)	17.5 (9.1 to 29.1)
Headache: Severe	3.2 (0.4 to 11.2)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	1.7 (0.0 to 8.9)	0 (0.0 to 5.7)
Headache: Grade 4	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Chills: Any	22.6 (12.9 to 35.0)	18.0 (9.4 to 30.0)	28.3 (17.5 to 41.4)	13.3 (5.9 to 24.6)	19.0 (10.2 to 30.9)
Chills: Mild	11.3 (4.7 to 21.9)	11.5 (4.7 to 22.2)	18.3 (9.5 to 30.4)	8.3 (2.8 to 18.4)	12.7 (5.6 to 23.5)
Chills: Moderate	11.3 (4.7 to 21.9)	6.6 (1.8 to 15.9)	10.0 (3.8 to 20.5)	5.0 (1.0 to 13.9)	6.3 (1.8 to 15.5)
Chills: Severe	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Chills: Grade 4	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Vomiting: Any	0 (0.0 to 5.8)	1.6 (0.0 to 8.8)	3.3 (0.4 to 11.5)	5.0 (1.0 to 13.9)	1.6 (0.0 to 8.5)
Vomiting: Mild	0 (0.0 to 5.8)	0 (0.0 to 5.9)	3.3 (0.4 to 11.5)	1.7 (0.0 to 8.9)	1.6 (0.0 to 8.5)
Vomiting: Moderate	0 (0.0 to 5.8)	1.6 (0.0 to 8.8)	0 (0.0 to 6.0)	3.3 (0.4 to 11.5)	0 (0.0 to 5.7)
Vomiting: Severe	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Vomiting: Grade 4	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Diarrhea: Any	12.9 (5.7 to 23.9)	6.6 (1.8 to 15.9)	16.7 (8.3 to 28.5)	16.7 (8.3 to 28.5)	12.7 (5.6 to 23.5)
Diarrhea: Mild	9.7 (3.6 to 19.9)	6.6 (1.8 to 15.9)	15.0 (7.1 to 26.6)	13.3 (5.9 to 24.6)	11.1 (4.6 to 21.6)
Diarrhea: Moderate	3.2 (0.4 to 11.2)	0 (0.0 to 5.9)	1.7 (0.0 to 8.9)	3.3 (0.4 to 11.5)	1.6 (0.0 to 8.5)
Diarrhea: Severe	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
Diarrhea: Grade 4	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
New or worsened muscle pain: Any	25.8 (15.5 to 38.5)	21.3 (11.9 to 33.7)	45.0 (32.1 to 58.4)	30.0 (18.8 to 43.2)	27.0 (16.6 to 39.7)
New or worsened muscle pain: Mild	19.4 (10.4 to 31.4)	8.2 (2.7 to 18.1)	23.3 (13.4 to 36.0)	11.7 (4.8 to 22.6)	12.7 (5.6 to 23.5)
New or worsened muscle pain: Moderate	6.5 (1.8 to 15.7)	11.5 (4.7 to 22.2)	21.7 (12.1 to 34.2)	18.3 (9.5 to 30.4)	14.3 (6.7 to 25.4)
New or worsened muscle pain: Severe	0 (0.0 to 5.8)	1.6 (0.0 to 8.8)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
New or worsened muscle pain: Grade 4	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
New or worsened joint pain: Any	14.5 (6.9 to 25.8)	14.8 (7.0 to 26.2)	5.0 (1.0 to 13.9)	13.3 (5.9 to 24.6)	17.5 (9.1 to 29.1)
New or worsened joint pain: Mild	9.7 (3.6 to 19.9)	6.6 (1.8 to 15.9)	0 (0.0 to 6.0)	3.3 (0.4 to 11.5)	7.9 (2.6 to 17.6)
New or worsened joint pain: Moderate	4.8 (1.0 to 13.5)	8.2 (2.7 to 18.1)	5.0 (1.0 to 13.9)	10.0 (3.8 to 20.5)	9.5 (3.6 to 19.6)
New or worsened joint pain: Severe	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)
New or worsened joint pain: Grade 4	0 (0.0 to 5.8)	0 (0.0 to 5.9)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)

No statistical analyses for this end point

Primary: Cohort 4: Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination

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End point title

Cohort 4: Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination ^[58] ^[59]

End point description

An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. Results excluded local reactions and systemic events data. Safety population included all participants who received the study intervention and where appropriate informed consent was obtained.

End point type

Primary

End point timeframe

From study vaccination through 1 month after study vaccination

Notes
[58] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 4 reporting groups only.

End point values	C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)
Number of subjects analysed	62	62	60	60	63
Units: Percentage of participants
number (confidence interval 95%)	8.1 (2.7 to 17.8)	9.7 (3.6 to 19.9)	1.7 (0.0 to 8.9)	1.7 (0.0 to 8.9)	1.6 (0.0 to 8.5)

No statistical analyses for this end point

Primary: Cohort 4: Percentage of Participants With SAEs From Study Vaccination Through 6 Months After Study Vaccination

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End point title

Cohort 4: Percentage of Participants With SAEs From Study Vaccination Through 6 Months After Study Vaccination ^[60] ^[61]

End point description

An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was an AE that 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 the study intervention and where appropriate informed consent was obtained.

End point type

Primary

End point timeframe

From study vaccination through 6 months after study vaccination

Notes
[60] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 4 reporting groups only.

End point values	C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)
Number of subjects analysed	62	62	60	60	63
Units: Percentage of participants
number (confidence interval 95%)	1.6 (0.0 to 8.7)	0 (0.0 to 5.8)	0 (0.0 to 6.0)	0 (0.0 to 6.0)	0 (0.0 to 5.7)

No statistical analyses for this end point

Primary: Cohort 4: GMT of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain NTs at 1 Month- Participants With or Without Evidence of Infection

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End point title

Cohort 4: GMT of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain NTs at 1 Month- Participants With or Without Evidence of Infection ^[62] ^[63]

End point description

End point type

Primary

End point timeframe

1 month after the study vaccination

Notes
[62] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[63] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 4 reporting groups only.

End point values	C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)
Number of subjects analysed	61	61	57	56	61
Units: Titer
geometric mean (confidence interval 95%)
Omicron BA.4/BA.5 (n=61,61,57,56,61)	4850.5 (3677.1 to 6398.3)	4854.3 (3713.9 to 6344.9)	4944.6 (3620.3 to 6753.1)	5180.6 (3724.6 to 7205.8)	5455.6 (4214.2 to 7062.8)
Reference strain (n=61,61,57,56,61)	10455.0 (8150.7 to 13410.8)	11360.0 (9408.3 to 13716.6)	10840.2 (8475.3 to 13865.0)	12303.8 (9728.6 to 15560.5)	11164.3 (8729.0 to 14279.0)

No statistical analyses for this end point

Primary: Cohort 4: GMT of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain NTs at Baseline

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End point title

Cohort 4: GMT of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain NTs at Baseline ^[64] ^[65]

End point description

End point type

Primary

End point timeframe

At baseline (before study vaccination)

Notes
[64] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[65] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 4 reporting groups only.

End point values	C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)
Number of subjects analysed	61	61	57	56	61
Units: Titer
geometric mean (confidence interval 95%)
Omicron BA.4/BA.5 (n= 61,61,57,56,61)	1332.5 (909.2 to 1953.0)	1313.6 (922.6 to 1870.2)	1352.0 (876.0 to 2086.8)	1320.1 (869.8 to 2003.6)	1203.9 (796.5 to 1819.6)
Reference strain (n= 61,61,57,56,61)	3445.5 (2465.4 to 4815.3)	4907.1 (3753.0 to 6416.1)	4613.6 (3474.3 to 6126.4)	4395.7 (3244.1 to 5956.3)	4318.6 (3196.1 to 5835.2)

No statistical analyses for this end point

Primary: Cohort 4: GMFR of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants With or Without Evidence of Infection

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End point title

Cohort 4: GMFR of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants With or Without Evidence of Infection ^[66] ^[67]

End point description

GMFR from before study vaccination to 1 month after study vaccination for each strain-specific neutralising titer was reported in this endpoint. GMFRs and 2-sided 95% CIs were calculated by exponentiating mean logarithm of fold rises and corresponding CIs (based on student-t distribution). Assay results below LLOQ were set to 0.5*LLOQ in analysis. EIP included all eligible randomised/assigned participants who received study intervention to which they were randomised/assigned, had at least 1 valid and determinate immunogenicity result from blood sample collected within 28-42 days after study vaccination, and had no other important protocol deviations as determined by clinician. Analysis was performed in participants with or without evidence of infection up to 1 month post study vaccination. Here, ''n’’ signifies participants evaluable for specified rows.

End point type

Primary

End point timeframe

1 month after study vaccination

Notes
[66] - 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: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[67] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 4 reporting groups only.

End point values	C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)
Number of subjects analysed	61	61	57	56	61
Units: Fold rise
geometric mean (confidence interval 95%)
Omicron BA.4/BA.5 (n=61,61,57,56,61)	3.6 (2.7 to 4.8)	3.7 (2.7 to 5.0)	3.7 (2.8 to 4.7)	3.9 (2.9 to 5.3)	4.5 (3.3 to 6.2)
Reference strain (n=61,61,57,56,61)	3.0 (2.3 to 4.0)	2.3 (1.8 to 3.0)	2.3 (1.9 to 2.8)	2.8 (2.1 to 3.7)	2.6 (2.1 to 3.2)

No statistical analyses for this end point

Primary: Cohort 4: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain– NTs at 1 Month After Study Vaccination- Participants With or Without Evidence of Infection

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End point title

Cohort 4: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain– NTs at 1 Month After Study Vaccination- Participants With or Without Evidence of Infection ^[68] ^[69]

End point description

Seroresponse was defined as achieving >= 4-fold rise in NTs from baseline (before the study vaccination). If the baseline measurement was below the LLOQ, the postvaccination measure of >= 4*LLOQ was considered a seroresponse. Percentage of participants with seroresponse to OMI BA.4/BA.5, XBB.1.5 and reference strain NTs at 1 month after study vaccination are presented as descriptive data. EIP included all eligible randomised/assigned participants who received study intervention to which they were randomised/assigned, had at least 1 valid and determinate immunogenicity result from blood sample collected within 28-42 days after study vaccination, and had no other important protocol deviations as determined by clinician. Analysis was performed in participants with or without evidence of infection up to 1 month post study vaccination. Here, ''n’’ signifies participants evaluable for specified rows.

End point type

Primary

End point timeframe

1 month after the study vaccination

Notes
[68] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive data was planned to be analysed for this endpoint.
[69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 4 reporting groups only.

End point values	C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)
Number of subjects analysed	61	61	57	56	61
Units: Percentage of participants
number (confidence interval 95%)
Omicron BA.4/BA.5 (n=61,61,57,56,61)	42.6 (30.0 to 55.9)	41.0 (28.6 to 54.3)	42.1 (29.1 to 55.9)	39.3 (26.5 to 53.2)	44.3 (31.5 to 57.6)
Reference strain (n=61,61,57,56,61)	37.7 (25.6 to 51.0)	27.9 (17.1 to 40.8)	22.8 (12.7 to 35.8)	26.8 (15.8 to 40.3)	29.5 (18.5 to 42.6)

No statistical analyses for this end point

Secondary: GMR of the Reference-Strain– NTs of BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg Cohort 2 (Group 4)/ Cohort 3 (Group 2) Combined in C4591044 Compared to NT of BNT162b2 30mcg in C4591031 >55 Years of age– 1 Month After Vaccination

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End point title

GMR of the Reference-Strain– NTs of BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg Cohort 2 (Group 4)/ Cohort 3 (Group 2) Combined in C4591044 Compared to NT of BNT162b2 30mcg in C4591031 >55 Years of age– 1 Month After Vaccination ^[70]

End point description

Model based GMT of reference strain NTs induced by BNT Bivalent 30mcg groups of study C4591044 [NCT05472038] Cohort 2/3 combined; BNT 30mcg of study C4591031 [NCT04955626] Substudy E in participants >55 years presented as descriptive data. GMT and 2-sided 95% CI calculated by exponentiating LS means and corresponding CI based on analysis of logarithmically transformed NT using linear regression model with terms of baseline NT (log scale) and vaccine group. Assay results below LLOQ=0.5*LLOQ. Model based GMR: OMI BA.4/BA.5 NTs induced 1 month after BNT Bivalent vaccination in study C4591044 to 1 month after BNT vaccination in study C4591031 in participants >55 years reported in statistical section. Endpoint was planned per protocol to analyse in participants from C2 G4+C3 G2 and BNT experienced participants >55 years from study C4591031 Substudy E (control arm). Analysis= EIP with/without evidence of infection up to 1 month post vaccination. "N"= participants evaluable for endpoint.

End point type

Secondary

End point timeframe

1 month after study vaccination

Notes
[70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2+3 reporting groups only.

End point values	C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)	BNT162b2 30 mcg: C4591031 Substudy E
Number of subjects analysed	284	287
Units: Titer
geometric mean (confidence interval 95%)	15361.6 (14082.9 to 16756.5)	11117.2 (10196.4 to 12121.1)

C2 (G2)+C3 (G1) Vs C4591031 Sub study E

Statistical analysis description

Noninferiority based on model-based GMR was declared if the lower limit of the 2-sided 95% CI for the model-based GMR is greater than 0.67.

Comparison groups

C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg) v BNT162b2 30 mcg: C4591031 Substudy E

Number of subjects included in analysis

571

Analysis specification

Pre-specified

Analysis type

non-inferiority

Method

Parameter type

Model-Based GMR

Point estimate

1.38

Confidence interval

level

95%

sides

2-sided

lower limit

1.22

upper limit

1.56

Secondary: Cohort 2/Group 2 + Cohort 3/Group 1 Combined and Cohort 2/Group 4 + Cohort 3/Group 2 Combined: GMT of SARS-CoV-2 Omicron BA.4/BA.5 and Reference Strain NT at Baseline and 1 Month After the Study Vaccination

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End point title

Cohort 2/Group 2 + Cohort 3/Group 1 Combined and Cohort 2/Group 4 + Cohort 3/Group 2 Combined: GMT of SARS-CoV-2 Omicron BA.4/BA.5 and Reference Strain NT at Baseline and 1 Month After the Study Vaccination ^[71]

End point description

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). This endpoint was planned per protocol to be analysed in participants from Cohort 2 Group 2 + Cohort 3 Group 1, Cohort 2 Group 4 + Cohort 3 Group 2 and control arm of BNT162b2 experienced participants >55 years of age from study C4591031 Substudy E. Analysis was performed in EIP with or without evidence of infection up to 1 month post study vaccination. Here, "Number of Participants Analysed": participants evaluable for this endpoint and ''n’’ signifies participants evaluable for specified rows.

End point type

Secondary

End point timeframe

At baseline and 1 month after study vaccination

Notes
[71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2+3 reporting groups only.

End point values	C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)	C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)	BNT162b2 30 mcg: C4591031 Substudy E
Number of subjects analysed	297	286	289
Units: Titer
geometric mean (confidence interval 95%)
Omicron BA.4/BA.5 at baseline(n=294,284,278)	569.6 (471.4 to 688.2)	458.2 (365.2 to 574.8)	205.4 (170.3 to 247.7)
Omicron BA.4/BA.5 at 1 Month(n=297,284,282)	4455.9 (3851.7 to 5154.8)	4158.1 (3554.8 to 4863.8)	938.9 (802.3 to 1098.8)
Reference strain at baseline(n=296,284,287)	4017.3 (3430.7 to 4704.1)	3690.6 (3082.2 to 4419.0)	2699.9 (2291.7 to 3180.9)
Reference strain at 1 Month(n=296,286,289)	16323.3 (14686.5 to 18142.6)	16250.1 (14499.2 to 18212.4)	10415.5 (9366.7 to 11581.8)

No statistical analyses for this end point

Secondary: Cohort 2/Group 2 + Cohort 3/Group 1 Combined and Cohort 2/Group 4 + Cohort 3/Group 2 Combined: Percentages of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain– NTs at 1 Month After the Study Vaccination

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End point title

Cohort 2/Group 2 + Cohort 3/Group 1 Combined and Cohort 2/Group 4 + Cohort 3/Group 2 Combined: Percentages of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain– NTs at 1 Month After the Study Vaccination ^[72]

End point description

Seroresponse was defined as achieving >= 4-fold rise in NTs from baseline (before study vaccination). If baseline measurement was below LLOQ, postvaccination measure of >= 4*LLOQ was considered seroresponse. Percentage of participants with seroresponse to OMI BA.4/BA.5 for BNT162b2 Bivalent 30 mcg in Study C4591044 [NCT05472038] Cohort 2/3 combined and BNT162b2 30 mcg in Study C4591031 [NCT04955626] Substudy E among participants >55 years of age are presented as descriptive data. This endpoint was planned per protocol to be analysed in participants from Cohort 2 Group 2 + Cohort 3 Group 1, Cohort 2 Group 4 + Cohort 3 Group 2 and control arm of BNT162b2 experienced participants >55 years of age from study C4591031 Substudy E. Analysis was performed in EIP with or without evidence of infection up to 1 month post study vaccination. "Number of Participants Analysed" signifies participants evaluable for this endpoint and ''n'' signifies participants evaluable for the specified rows.

End point type

Secondary

End point timeframe

1 month after the study vaccination

Notes
[72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2+3 reporting groups only.

End point values	C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)	C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)	BNT162b2 30 mcg: C4591031 Substudy E
Number of subjects analysed	295	284	287
Units: Percentage of participants
number (confidence interval 95%)
Omicron BA.4/BA.5(n=294,282,273)	61.2 (55.4 to 66.8)	66.7 (60.8 to 72.1)	46.5 (40.5 to 52.6)
Reference strain(n=295,284,287)	44.1 (38.3 to 49.9)	45.8 (39.9 to 51.8)	48.1 (42.2 to 54.0)

No statistical analyses for this end point

Secondary: Cohort 2/Group 2 + Cohort 3/Group 1 Combined and Cohort 2/Group 4 + Cohort 3/Group 2 Combined: GMFR of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination

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End point title

Cohort 2/Group 2 + Cohort 3/Group 1 Combined and Cohort 2/Group 4 + Cohort 3/Group 2 Combined: GMFR of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination ^[73]

End point description

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. GMFR from before the study vaccination to 1 month after study vaccination for Omicron BA.4/BA.5 and reference strain neutralising titer was reported in this endpoint. This endpoint was planned per protocol to be analysed in participants from Cohort 2 Group 2 + Cohort 3 Group 1, Cohort 2 Group 4 + Cohort 3 Group 2 and control arm of BNT162b2 experienced participants >55 years of age from study C4591031 Substudy E. Analysis was performed in EIP with or without evidence of infection up to 1 month post study vaccination. Here, "Number of Participants Analysed" signifies participants evaluable for this endpoint and ''n’’ signifies participants evaluable for specified rows.

End point type

Secondary

End point timeframe

From before the study vaccination to 1 month after study vaccination

Notes
[73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Per protocol, this analysis was planned to be analysed in Cohort 2+3 reporting groups only.

End point values	C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)	C2G4+C3G2:>55 Years(BNT162b2 Bivalent [WT/OMI BA.4/BA.5]30mcg)	BNT162b2 30 mcg: C4591031 Substudy E
Number of subjects analysed	295	284	287
Units: Fold rise
geometric mean (confidence interval 95%)
Omicron BA.4/BA.5 (n=294,282,273)	7.8 (6.7 to 9.2)	8.9 (7.5 to 10.6)	4.6 (4.0 to 5.2)
Reference strain (n=295,284,287)	4.1 (3.6 to 4.6)	4.4 (3.8 to 5.1)	3.9 (3.4 to 4.4)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Local reactions and systemic events: From Day 1 to Day 7 after study vaccination; AE: From study vaccination on Day 1 through 1 month after study vaccination, SAE and Death: From study vaccination on Day 1 through 6 months after study vaccination

Adverse event reporting additional description

Same event may appear as non-SAE and SAE, what is presented are distinct. Event may be categorised as serious in 1 and non-serious in other, or participant may experience both SAE and non-SAE. Safety population. Per analysis planned, data is summarised and combined for C2/C3 30mcg groups per age category. MedDRA for C1/C4: v27.0; for C2/C3: v26.0.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

C 2 G 1: 12-17 Years (BNT162b2 [WT/OMI BA.4/BA.5] 30 mcg)

Reporting group description

Participants aged 12-17 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C 2 G 3: 18-55 Years (BNT162b2 [WT/OMI BA.4/BA.5] 60 mcg)

Reporting group description

Participants aged 18-55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 60 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C2G4+C3G2:>55 Years (BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged more than (>) 55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C 2 G 5: >55 Years (BNT162b2 [WT/OMI BA.4/BA.5] 60 mcg)

Reporting group description

Participants aged >55 years received BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 60 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)

Reporting group description

Participants aged 18-55 years received BNT162b5 Bivalent (WT/OMI BA.2) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b6 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)

Reporting group description

Participants aged 18-55 years received BNT162b2 Bivalent (WT/OMI BA.1) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b2 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b5 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Reporting group description

Participants aged 18-55 years received BNT162b7 Bivalent (Original/OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

Reporting group title

C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)

Reporting group description

Participants aged 18-55 years received BNT162b7 Monovalent (OMI BA.4/BA.5) 30 mcg intramuscularly at Visit 1 (Day 1).

C 2 G 1: 12-17 Years (BNT162b2 [WT/OMI BA.4/BA.5] 30 mcg)

C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)

C 2 G 3: 18-55 Years (BNT162b2 [WT/OMI BA.4/BA.5] 60 mcg)

C2G4+C3G2:>55 Years (BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)

C 2 G 5: >55 Years (BNT162b2 [WT/OMI BA.4/BA.5] 60 mcg)

Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)

C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)

Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)

C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)

C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)

C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)

C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)

Total subjects affected by serious adverse events

subjects affected / exposed

1 / 107 (0.93%)

2 / 313 (0.64%)

1 / 110 (0.91%)

10 / 306 (3.27%)

0 / 102 (0.00%)

1 / 104 (0.96%)

0 / 60 (0.00%)

2 / 102 (1.96%)

1 / 62 (1.61%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma pancreas

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

1 / 306 (0.33%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Leukaemia

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

1 / 306 (0.33%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Testicular germ cell cancer

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

1 / 110 (0.91%)

0 / 306 (0.00%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Prostate cancer

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

1 / 306 (0.33%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Hypotension

subjects affected / exposed

0 / 107 (0.00%)

1 / 313 (0.32%)

0 / 110 (0.00%)

0 / 306 (0.00%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Suicidal ideation

subjects affected / exposed

1 / 107 (0.93%)

0 / 313 (0.00%)

0 / 110 (0.00%)

0 / 306 (0.00%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Alcohol poisoning

subjects affected / exposed

1 / 107 (0.93%)

0 / 313 (0.00%)

0 / 110 (0.00%)

0 / 306 (0.00%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Arrhythmia

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

1 / 306 (0.33%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Left ventricular failure

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

1 / 306 (0.33%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Nervous system disorders

Syncope

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

1 / 306 (0.33%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Normocytic anaemia

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

0 / 306 (0.00%)

0 / 102 (0.00%)

1 / 104 (0.96%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Pancreatitis acute

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

0 / 306 (0.00%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

1 / 102 (0.98%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal obstruction

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

0 / 306 (0.00%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

1 / 102 (0.98%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Biliary colic

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

0 / 306 (0.00%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

1 / 102 (0.98%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Urinary tract obstruction

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

1 / 306 (0.33%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Acute kidney injury

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

0 / 306 (0.00%)

0 / 102 (0.00%)

1 / 104 (0.96%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Back pain

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

1 / 306 (0.33%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Diverticulitis

subjects affected / exposed

0 / 107 (0.00%)

1 / 313 (0.32%)

0 / 110 (0.00%)

0 / 306 (0.00%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Post procedural infection

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

1 / 306 (0.33%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

0 / 306 (0.00%)

0 / 102 (0.00%)

1 / 104 (0.96%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Enterocolitis infectious

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

0 / 306 (0.00%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

1 / 62 (1.61%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Hypoglycaemia

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

1 / 306 (0.33%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypokalaemia

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

1 / 306 (0.33%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Type 2 diabetes mellitus

subjects affected / exposed

0 / 107 (0.00%)

0 / 313 (0.00%)

0 / 110 (0.00%)

1 / 306 (0.33%)

0 / 102 (0.00%)

0 / 104 (0.00%)

0 / 60 (0.00%)

0 / 102 (0.00%)

0 / 62 (0.00%)

0 / 60 (0.00%)

0 / 63 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	C 2 G 1: 12-17 Years (BNT162b2 [WT/OMI BA.4/BA.5] 30 mcg)	C2G2+C3G1:18-55Years(BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)	C 2 G 3: 18-55 Years (BNT162b2 [WT/OMI BA.4/BA.5] 60 mcg)	C2G4+C3G2:>55 Years (BNT162b2 Bivalent[WT/OMI BA.4/BA.5]30mcg)	C 2 G 5: >55 Years (BNT162b2 [WT/OMI BA.4/BA.5] 60 mcg)	Cohort 1: 18-55 Years (BNT162b5 Bivalent [WT/OMI BA.2] 30 mcg)	C4:18-55 Years(BNT162b6 Bivalent[Original/OMI BA.4/BA.5]30mcg)	Cohort 1: 18-55 Years (BNT162b2 Bivalent [WT/OMI BA.1] 30 mcg)	C4:18-55 Years(BNT162b2 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b5 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4:18-55 Years(BNT162b7 Bivalent[Original/OMI BA.4/BA.5]30mcg)	C4: 18-55 Years (BNT162b7 Monovalent [OMI BA.4/BA.5] 30 mcg)
Total subjects affected by non serious adverse events
subjects affected / exposed	96 / 107 (89.72%)	269 / 313 (85.94%)	106 / 110 (96.36%)	210 / 306 (68.63%)	82 / 102 (80.39%)	97 / 104 (93.27%)	52 / 60 (86.67%)	91 / 102 (89.22%)	55 / 62 (88.71%)	56 / 62 (90.32%)	53 / 60 (88.33%)	56 / 63 (88.89%)
Investigations
Blood pressure increased
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 60 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1
Injury, poisoning and procedural complications
Thermal burn
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 60 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
Nervous system disorders
Headache (HEADACHE)
alternative assessment type: Systematic
subjects affected / exposed	54 / 107 (50.47%)	144 / 313 (46.01%)	50 / 110 (45.45%)	92 / 306 (30.07%)	36 / 102 (35.29%)	55 / 104 (52.88%)	25 / 60 (41.67%)	47 / 102 (46.08%)	37 / 62 (59.68%)	22 / 62 (35.48%)	28 / 60 (46.67%)	25 / 63 (39.68%)
occurrences all number	54	144	50	92	36	55	25	47	37	22	28	25
Bell's palsy
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 60 (0.00%)	1 / 63 (1.59%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1
Headache
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 60 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	0 / 107 (0.00%)	6 / 313 (1.92%)	1 / 110 (0.91%)	1 / 306 (0.33%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 60 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	6	1	1	0	0	0	0	0	1	0	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	3 / 107 (2.80%)	2 / 313 (0.64%)	1 / 110 (0.91%)	1 / 306 (0.33%)	0 / 102 (0.00%)	0 / 104 (0.00%)	1 / 60 (1.67%)	0 / 102 (0.00%)	1 / 62 (1.61%)	1 / 62 (1.61%)	1 / 60 (1.67%)	0 / 63 (0.00%)
occurrences all number	3	2	1	1	0	0	1	0	1	1	1	0
Chills (CHILLS)
alternative assessment type: Systematic
subjects affected / exposed	25 / 107 (23.36%)	68 / 313 (21.73%)	30 / 110 (27.27%)	36 / 306 (11.76%)	23 / 102 (22.55%)	22 / 104 (21.15%)	17 / 60 (28.33%)	20 / 102 (19.61%)	14 / 62 (22.58%)	11 / 62 (17.74%)	8 / 60 (13.33%)	12 / 63 (19.05%)
occurrences all number	25	68	30	36	23	22	17	20	14	11	8	12
Fatigue (FATIGUE)
alternative assessment type: Systematic
subjects affected / exposed	72 / 107 (67.29%)	189 / 313 (60.38%)	76 / 110 (69.09%)	115 / 306 (37.58%)	54 / 102 (52.94%)	76 / 104 (73.08%)	44 / 60 (73.33%)	64 / 102 (62.75%)	38 / 62 (61.29%)	39 / 62 (62.90%)	39 / 60 (65.00%)	34 / 63 (53.97%)
occurrences all number	72	189	76	115	54	76	44	64	38	39	39	34
Injection site erythema (REDNESS)
alternative assessment type: Systematic
subjects affected / exposed	6 / 107 (5.61%)	20 / 313 (6.39%)	12 / 110 (10.91%)	11 / 306 (3.59%)	7 / 102 (6.86%)	6 / 104 (5.77%)	3 / 60 (5.00%)	6 / 102 (5.88%)	3 / 62 (4.84%)	2 / 62 (3.23%)	1 / 60 (1.67%)	1 / 63 (1.59%)
occurrences all number	6	20	12	11	7	6	3	6	3	2	1	1
Injection site pain (PAIN)
alternative assessment type: Systematic
subjects affected / exposed	75 / 107 (70.09%)	235 / 313 (75.08%)	103 / 110 (93.64%)	171 / 306 (55.88%)	71 / 102 (69.61%)	86 / 104 (82.69%)	45 / 60 (75.00%)	83 / 102 (81.37%)	52 / 62 (83.87%)	54 / 62 (87.10%)	46 / 60 (76.67%)	52 / 63 (82.54%)
occurrences all number	75	235	103	171	71	86	45	83	52	54	46	52
Injection site pain
subjects affected / exposed	2 / 107 (1.87%)	2 / 313 (0.64%)	0 / 110 (0.00%)	1 / 306 (0.33%)	1 / 102 (0.98%)	0 / 104 (0.00%)	2 / 60 (3.33%)	0 / 102 (0.00%)	1 / 62 (1.61%)	3 / 62 (4.84%)	1 / 60 (1.67%)	3 / 63 (4.76%)
occurrences all number	2	2	0	1	1	0	2	0	1	3	1	3
Injection site swelling (SWELLING)
alternative assessment type: Systematic
subjects affected / exposed	8 / 107 (7.48%)	22 / 313 (7.03%)	17 / 110 (15.45%)	8 / 306 (2.61%)	9 / 102 (8.82%)	11 / 104 (10.58%)	4 / 60 (6.67%)	11 / 102 (10.78%)	1 / 62 (1.61%)	2 / 62 (3.23%)	2 / 60 (3.33%)	2 / 63 (3.17%)
occurrences all number	8	22	17	8	9	11	4	11	1	2	2	2
Pyrexia (FEVER)
alternative assessment type: Systematic
subjects affected / exposed	10 / 107 (9.35%)	15 / 313 (4.79%)	13 / 110 (11.82%)	13 / 306 (4.25%)	14 / 102 (13.73%)	2 / 104 (1.92%)	6 / 60 (10.00%)	6 / 102 (5.88%)	4 / 62 (6.45%)	4 / 62 (6.45%)	3 / 60 (5.00%)	6 / 63 (9.52%)
occurrences all number	10	15	13	13	14	2	6	6	4	4	3	6
Ear and labyrinth disorders
Ear pain
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 60 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0
Gastrointestinal disorders
Diarrhoea (DIARRHEA)
alternative assessment type: Systematic
subjects affected / exposed	7 / 107 (6.54%)	33 / 313 (10.54%)	14 / 110 (12.73%)	28 / 306 (9.15%)	7 / 102 (6.86%)	15 / 104 (14.42%)	10 / 60 (16.67%)	20 / 102 (19.61%)	8 / 62 (12.90%)	4 / 62 (6.45%)	10 / 60 (16.67%)	8 / 63 (12.70%)
occurrences all number	7	33	14	28	7	15	10	20	8	4	10	8
Vomiting (VOMITING)
alternative assessment type: Systematic
subjects affected / exposed	3 / 107 (2.80%)	6 / 313 (1.92%)	2 / 110 (1.82%)	2 / 306 (0.65%)	3 / 102 (2.94%)	1 / 104 (0.96%)	2 / 60 (3.33%)	2 / 102 (1.96%)	0 / 62 (0.00%)	1 / 62 (1.61%)	3 / 60 (5.00%)	1 / 63 (1.59%)
occurrences all number	3	6	2	2	3	1	2	2	0	1	3	1
Vomiting
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 60 (1.67%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
Diarrhoea
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 60 (1.67%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
Reproductive system and breast disorders
Vulvovaginal pruritus
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 60 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
Musculoskeletal and connective tissue disorders
Myalgia (MUSCLE PAIN)
alternative assessment type: Systematic
subjects affected / exposed	28 / 107 (26.17%)	94 / 313 (30.03%)	46 / 110 (41.82%)	54 / 306 (17.65%)	23 / 102 (22.55%)	37 / 104 (35.58%)	27 / 60 (45.00%)	39 / 102 (38.24%)	16 / 62 (25.81%)	13 / 62 (20.97%)	17 / 60 (28.33%)	17 / 63 (26.98%)
occurrences all number	28	94	46	54	23	37	27	39	16	13	17	17
Myalgia
subjects affected / exposed	2 / 107 (1.87%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	1 / 60 (1.67%)	0 / 102 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 60 (1.67%)	0 / 63 (0.00%)
occurrences all number	2	0	0	0	0	0	1	0	0	0	1	0
Arthralgia (JOINT PAIN)
alternative assessment type: Systematic
subjects affected / exposed	13 / 107 (12.15%)	46 / 313 (14.70%)	27 / 110 (24.55%)	36 / 306 (11.76%)	15 / 102 (14.71%)	19 / 104 (18.27%)	3 / 60 (5.00%)	18 / 102 (17.65%)	9 / 62 (14.52%)	9 / 62 (14.52%)	8 / 60 (13.33%)	11 / 63 (17.46%)
occurrences all number	13	46	27	36	15	19	3	18	9	9	8	11
Back pain
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	1 / 60 (1.67%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0
Infections and infestations
Sinusitis
subjects affected / exposed	2 / 107 (1.87%)	1 / 313 (0.32%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 62 (1.61%)	1 / 62 (1.61%)	0 / 60 (0.00%)	0 / 63 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0	1	1	0	0
Joint abscess
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 60 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0
COVID-19
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	3 / 104 (2.88%)	0 / 60 (0.00%)	4 / 102 (3.92%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 60 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	3	0	4	0	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 60 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
Vulvovaginal mycotic infection
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	0 / 62 (0.00%)	1 / 62 (1.61%)	0 / 60 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0
Otitis media
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	1 / 60 (1.67%)	0 / 102 (0.00%)	0 / 62 (0.00%)	0 / 62 (0.00%)	0 / 60 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 60 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0
Metabolism and nutrition disorders
Hypercholesterolaemia
subjects affected / exposed	0 / 107 (0.00%)	0 / 313 (0.00%)	0 / 110 (0.00%)	0 / 306 (0.00%)	0 / 102 (0.00%)	0 / 104 (0.00%)	0 / 60 (0.00%)	0 / 102 (0.00%)	1 / 62 (1.61%)	0 / 62 (0.00%)	0 / 60 (0.00%)	0 / 63 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

27 Jul 2022

Inclusion of a second cohort to describe the immune response to BNT162b2 Bivalent (WT/OMI BA.4/BA.5) at 30 mcg in individuals >=12 years of age and at 60 mcg in adults >=18 years of age. Added corresponding objectives, estimands, and endpoints and details in the statistical methods sections. Study intervention details and background information supporting inclusion of this cohort were added. Inclusion of prospective capture of confirmed COVID-19 cases for both Cohorts 1 and 2 with active COVID-19 surveillance and convalescent visits.

24 Aug 2022

Inclusion of a third cohort to allow for a sufficiently powered evaluation of BNT162b2 Bivalent (WT/OMI BA.4/BA.5) 30 mcg as a second booster dose in BNT162b2-experienced participants >=18 years of age. Added corresponding objectives, estimands, and endpoints and details in the statistical methods sections. Study intervention details and background information supporting inclusion of this cohort were added.

26 May 2023

Inclusion of a fourth cohort to describe the immune response to authorised and new 30 mcg Bivalent and Monovalent Omicron BA.4/BA.5–modified BNT162b vaccines: 1. BNT162b2 Bivalent (Original/OMI BA.4/BA.5) 2. BNT162b5 Bivalent (Original/OMI BA.4/BA.5) 3. BNT162b7 Bivalent (Original/OMI BA.4/BA.5) 4. BNT162b7 Monovalent (OMI BA.4/BA.5) given to mRNA COVID-19 vaccine–experienced participants 18 through 55 years of age. Added corresponding objectives, estimands, and endpoints and details in the statistical methods sections. Study intervention details and background information supporting the inclusion of this cohort were also added.

27 Jul 2023

Addition of BNT162b6 vaccine into Cohort 4 to describe the immune response to this new 30 mcg Bivalent Omicron BA.4/BA.5–modified BNT162b vaccine: BNT162b6 Bivalent (Original/OMI BA.4/BA.5) given to mRNA COVID 19 vaccine–experienced participants 18 through 55 years of age. Updated corresponding objectives and details in the statistical methods sections. Study intervention details and background information supporting the inclusion of this vaccine were also added.

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: An Interventional, Randomized, Active-Controlled, Phase 1/2/3 Study to Investigate the Safety, Tolerability, and Immunogenicity of BNT162b RNA-Based Vaccine Candidates in COVID-19 Vaccine-Experienced Healthy Individuals

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Cohort 1: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination

Primary: Cohort 1: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination

Primary: Cohort 1: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination

Primary: Cohort 1: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination

Primary: Cohort 1: Geometric Mean Titer (GMT) of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain Neutralising Titers (NTs) at Baseline- Participants Without Evidence of Infection

Primary: Cohort 1: Geometric Mean Titer (GMT) of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain Neutralising Titers (NTs) at Baseline- Participants Without Evidence of Infection

Primary: Cohort 1: Percentage of Participants With Adverse Events (AEs) From Study Vaccination Through 1 Month After Study Vaccination

Primary: Cohort 1: Percentage of Participants With Adverse Events (AEs) From Study Vaccination Through 1 Month After Study Vaccination

Primary: Cohort 1: Percentage of Participants With Serious Adverse Events (SAEs) From Study Vaccination Through 6 Months After Study Vaccination

Primary: Cohort 1: Percentage of Participants With Serious Adverse Events (SAEs) From Study Vaccination Through 6 Months After Study Vaccination

Primary: Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at Baseline- Participants With or Without Evidence of Infection

Primary: Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at Baseline- Participants With or Without Evidence of Infection

Primary: Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at 1 Month- Participants Without Evidence of Infection

Primary: Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at 1 Month- Participants Without Evidence of Infection

Primary: Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at 1 Month- Participants With or Without Evidence of Infection

Primary: Cohort 1: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain NTs at 1 Month- Participants With or Without Evidence of Infection

Primary: Cohort 1: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants Without Evidence of Infection

Primary: Cohort 1: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants Without Evidence of Infection

Primary: Cohort 1: GMFR of SARS-CoV-2 Omicron Strain (BA.1 and BA2) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants With or Without Evidence of Infection

Primary: Cohort 1: GMFR of SARS-CoV-2 Omicron Strain (BA.1 and BA2) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants With or Without Evidence of Infection

Primary: Cohort 1: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain– NTs at 1 Month After Study Vaccination- Participants Without Evidence of Infection

Primary: Cohort 1: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain– NTs at 1 Month After Study Vaccination- Participants Without Evidence of Infection

Primary: Cohort 1: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain– NTs at 1 Month After Study Vaccination- Participants With or Without Evidence of Infection

Primary: Cohort 1: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.1 and BA.2) and Reference Strain– NTs at 1 Month After Study Vaccination- Participants With or Without Evidence of Infection

Primary: Cohort 2: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination

Primary: Cohort 2: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination

Primary: Cohort 2: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination

Primary: Cohort 2: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination

Primary: Cohort 2: Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination

Primary: Cohort 2: Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination

Primary: Cohort 2: Percentage of Participants With SAEs From Study Vaccination Through 6 Months After Study Vaccination

Primary: Cohort 2: Percentage of Participants With SAEs From Study Vaccination Through 6 Months After Study Vaccination

Primary: Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and 2): Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination

Primary: Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and 2): Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination

Primary: Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination

Primary: Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination

Primary: Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination

Primary: Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination

Primary: Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants With SAEs From Study Vaccination Through 6 Months After Study Vaccination

Primary: Cohort 2 (Group 2 and 4) + Cohort 3 (Group 1 and Group 2): Percentage of Participants With SAEs From Study Vaccination Through 6 Months After Study Vaccination

Primary: GMR of Omicron (BA.4/BA.5)– NTs of BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg C2 G4/C3 G2 Combined in C4591044 Compared to NT of BNT162b2 30 mcg in C4591031– 1 Month After Vaccination Among Participants >55 Years of Age

Primary: GMR of Omicron (BA.4/BA.5)– NTs of BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg C2 G4/C3 G2 Combined in C4591044 Compared to NT of BNT162b2 30 mcg in C4591031– 1 Month After Vaccination Among Participants >55 Years of Age

Primary: Difference in Percentage of Participants With Seroresponse to OMI BA.4/BA.5 for BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg C2 G4/C3 G2 Combined in C4591044 and for BNT162b2 30 mcg in C4591031– 1 Month After Vaccination Among Participants >55 Years of Age

Primary: Difference in Percentage of Participants With Seroresponse to OMI BA.4/BA.5 for BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg C2 G4/C3 G2 Combined in C4591044 and for BNT162b2 30 mcg in C4591031– 1 Month After Vaccination Among Participants >55 Years of Age

Primary: GMR of Omicron (BA.4/BA.5)– NTs of BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg C2 G2/C3 G1 Combined for 18-55 Years Compared to BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg C2 G4/C3 G2 Combined for >55 Years– 1 Month After Vaccination in C4591044

Primary: GMR of Omicron (BA.4/BA.5)– NTs of BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30 mcg C2 G2/C3 G1 Combined for 18-55 Years Compared to BNT162b2 Bivalent [WT/OMI BA.4/BA.5] 30mcg C2 G4/C3 G2 Combined for >55 Years– 1 Month After Vaccination in C4591044

Primary: Difference in Percentage of Participants With Seroresponse to OMI BA.4/BA.5 of BNT162b2 30mcg Cohort 2 (Group 2)/ Cohort 3 (Group 1) 18-55 Years of age and Cohort 2 (Group 4)/ Cohort 3 (Group 2) >55 Years of age– 1 Month After Vaccination in C4591044

Primary: Difference in Percentage of Participants With Seroresponse to OMI BA.4/BA.5 of BNT162b2 30mcg Cohort 2 (Group 2)/ Cohort 3 (Group 1) 18-55 Years of age and Cohort 2 (Group 4)/ Cohort 3 (Group 2) >55 Years of age– 1 Month After Vaccination in C4591044

Primary: Cohort 2: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain NTs at Baseline

Primary: Cohort 2: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain NTs at Baseline

Primary: Cohort 2: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain NTs at 1 Month

Primary: Cohort 2: GMT of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain NTs at 1 Month

Primary: Cohort 2: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination

Primary: Cohort 2: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination

Primary: Cohort 2: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain– NTs at 1 Month After Study Vaccination

Primary: Cohort 2: Percentage of Participants With Seroresponse to SARS-CoV-2 Omicron Strain (BA.1 and BA.4/BA.5) and Reference Strain– NTs at 1 Month After Study Vaccination

Primary: Cohort 4: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination

Primary: Cohort 4: Percentage of Participants Reporting Local Reactions Within 7 Days After Study Vaccination

Primary: Cohort 4: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination

Primary: Cohort 4: Percentage of Participants Reporting Systemic Events Within 7 Days After Study Vaccination

Primary: Cohort 4: Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination

Primary: Cohort 4: Percentage of Participants With AEs From Study Vaccination Through 1 Month After Study Vaccination

Primary: Cohort 4: Percentage of Participants With SAEs From Study Vaccination Through 6 Months After Study Vaccination

Primary: Cohort 4: Percentage of Participants With SAEs From Study Vaccination Through 6 Months After Study Vaccination

Primary: Cohort 4: GMT of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain NTs at 1 Month- Participants With or Without Evidence of Infection

Primary: Cohort 4: GMT of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain NTs at 1 Month- Participants With or Without Evidence of Infection

Primary: Cohort 4: GMT of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain NTs at Baseline

Primary: Cohort 4: GMT of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain NTs at Baseline

Primary: Cohort 4: GMFR of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants With or Without Evidence of Infection

Primary: Cohort 4: GMFR of SARS-CoV-2 Omicron Strain (BA.4/BA.5) and Reference Strain– NTs From Before the Study Vaccination to 1 Month After the Study Vaccination- Participants With or Without Evidence of Infection

Clinical Trial Results:
An Interventional, Randomized, Active-Controlled, Phase 1/2/3 Study to Investigate the Safety, Tolerability, and Immunogenicity of BNT162b RNA-Based Vaccine Candidates in COVID-19 Vaccine-Experienced Healthy Individuals