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Clinical Trial Results:
A Phase II trial to evaluate the safety and immunogenicity of SARS-CoV-2 monovalent and multivalent RNA-based vaccines in healthy subjects

Summary
EudraCT number	2021-003458-22
Trial protocol	DE
Global end of trial date	04 Oct 2023

Results information
Results version number	v1(current)
This version publication date	18 Oct 2024
First version publication date	18 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

BNT162-17

ISRCTN number

US NCT number

NCT05004181

WHO universal trial number (UTN)

Other trial identifiers

US IND: 19736

Sponsor organisation name

BioNTech SE

Sponsor organisation address

An der Goldgrube 12, Mainz, Germany, 55131

Public contact

BioNTech SE, BioNTech SE, +49 613190840, patients@biontech.de

Scientific contact

BioNTech SE, BioNTech SE, +49 613190840, patients@biontech.de

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

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?

Analysis stage

Final

Date of interim/final analysis

20 Jun 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

04 Oct 2023

Was the trial ended prematurely?

Main objective of the trial

This trial consisted of Parts A, B, and C, and evaluated the safety and immunogenicity of a 3rd or 3rd and 4th doses of the multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), and one dose of the monovalent vaccines BNT162b2 (B.1.617.2), BNT162b2 (B.1.1.7) and BNT162b2, in participants who had received 2 doses of the parent vaccine BNT162b2 at 30 μg, at least 6 months after the 2nd dose of BNT162b2. It also evaluated the safety and immunogenicity of a 3-dose regimen of BNT162b2 (B.1.1.7 + B.1.617.2) in participants who had not received prior COVID-19 vaccination. In addition, the safety of BNT162b2 (B.1.1.529.1) or BNT162b2 given as a 3rd or 4th vaccine dose to RNA COVID-19 vaccine-experienced participants with history of SARSCoV-2 Omicron variant infection was evaluated and contrasted with the natural immune response reached after infection with the SARS-CoV-2 Omicron variant in RNA COVID-19 vaccine experienced participants.

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 Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.

Background therapy

Part A Cohorts 1-5 received BNT162b2 via either BNT162-02 / C4591001 (EudraCT number: 2020-002641-42) or by government available programs. Part B Cohorts 1 and 4 enrolled participants from the Phase III trial C4591001 (EudraCT number: 2020-002641-42) who had previously received two injections of 30 μg BNT162b2 (i.e., BNT162b2-experienced participants). Part C cohorts received mRNA COVID-19 vaccinations.

Evidence for comparator

Actual start date of recruitment

25 Aug 2021

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 86

Country: Number of subjects enrolled

United States: 737

Country: Number of subjects enrolled

Türkiye: 137

Country: Number of subjects enrolled

South Africa: 420

Worldwide total number of subjects

1380

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)

Adults (18-64 years)

1219

From 65 to 84 years

160

85 years and over

Subject disposition

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Recruitment details

The first participant signed ICF on 25 Aug 2021 and the last participant completed the study on 04 Oct 2023. Participants were eligible if they had received 2 doses of the parent vaccine BNT162b2 at 30 μg, and the second dose of BNT162b2 was at least 6 months ago (Part A Cohorts 1 to 5, Part B Cohorts 1 and 4).

Screening details

Participants were also eligible if they had not received prior Coronavirus Disease 2019 (COVID-19) vaccination (Part A Cohort 6, Part B Cohort 6) or had received 2 or 3 injections of any authorized COVID-19 RNA-based vaccine and were subsequently diagnosed with SARS-CoV-2 infection from Jan 2022 onwards.

Period 1 title

Overall study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part A - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Arm description

Participants in Part A - Cohort 1 received 1 dose of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection on Day 1

Arm type

Experimental

Investigational medicinal product name

BNT162b2 (B.1.1.7 + B.1.617.2)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscular (IM); upper arm, musculus deltoideus. The non-dominant arm was preferred.

Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Arm description

Participants in Part A - Cohort 2 received 2 doses of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection one on Day 1 and one on Day 56

Arm type

Experimental

Investigational medicinal product name

BNT162b2 (B.1.1.7 + B.1.617.2)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscular (IM); upper arm, musculus deltoideus. The same arm may be used for both immunizations. The non-dominant arm was preferred.

Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)

Arm description

Participants in Part A - Cohort 3 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.1.7) on Day 1

Arm type

Experimental

Investigational medicinal product name

BNT162b2 (B.1.1.7)

Investigational medicinal product code

Other name

Alpha

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscular (IM); upper arm, musculus deltoideus. The non-dominant arm was preferred.

Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)

Arm description

Participants in Part A - Cohort 4 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.617.2) on Day 1

Arm type

Experimental

Investigational medicinal product name

BNT162b2 (B.1.617.2)

Investigational medicinal product code

Other name

Delta

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscular (IM); upper arm, musculus deltoideus. The non-dominant arm was preferred.

Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)

Arm description

Participants in Part A - Cohort 5 received 1 dose of 30 μg BNT162b2 original vaccine on Day 1. 21 participants assigned to Part B Cohort 4 actually received BNT162b2 (treatment of Part A Cohort 5) and therefore were included in the analyses of safety set of Part A Cohort 5 and excluded from Part B safety set. 1 participant from Part A - Cohort 6 also received BNT162b2 and was included in the Part A - Cohort 5 safety set.

Arm type

Experimental

Investigational medicinal product name

BNT162b2 (Original Vaccine)

Investigational medicinal product code

Other name

Comirnaty

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscular (IM); upper arm, musculus deltoideus. The non-dominant arm was preferred.

Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Arm description

Participants in Part A - Cohort 6 received 3 doses of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), as a single injection one on Day 1, one on Day 21 and one approximately 6 months after the second dose

Arm type

Experimental

Investigational medicinal product name

BNT162b2 (B.1.1.7 + B.1.617.2)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscular (IM); upper arm, musculus deltoideus. The same arm may be used for all immunizations. The non-dominant arm was preferred.

Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Arm description

Participants in Part B - Cohort 1 received 1 dose of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection on Day 1

Arm type

Experimental

Investigational medicinal product name

BNT162b2 (B.1.1.7 + B.1.617.2)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscular (IM); upper arm, musculus deltoideus. The non-dominant arm was preferred.

Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)

Arm description

Participants in Part B - Cohort 4 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.617.2) on Day 1

Arm type

Experimental

Investigational medicinal product name

BNT162b2 (B.1.617.2)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscular (IM); upper arm, musculus deltoideus. The non-dominant arm was preferred.

Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Arm description

Participants in Part B - Cohort 6 received 3 doses of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), as a single injection one on Day 1, one on Day 21 and one approximately 6 months after the second dose

Arm type

Experimental

Investigational medicinal product name

BNT162b2 (B.1.1.7 + B.1.617.2)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscular (IM); upper arm, musculus deltoideus. The same arm may be used for all immunizations. The non-dominant arm was preferred.

Part C - C7: 1 Dose of 30 μg BNT162b2 (B.1.1.529.1)

Arm description

Participants in Part C - Cohort 7 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.1.529.1) on Day 1

Arm type

Experimental

Investigational medicinal product name

BNT162b2 (B.1.1.529.1)

Investigational medicinal product code

Other name

Omicron

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscular; upper arm, musculus deltoideus. The non-dominant arm was preferred.

Part C - C8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)

Arm description

Participants in Part C - Cohort 8 received 1 dose of 30 μg BNT162b2 original vaccine on Day 1

Arm type

Experimental

Investigational medicinal product name

BNT162b2 (Original Vaccine)

Investigational medicinal product code

Other name

Comirnaty

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Intramuscular (IM); upper arm, musculus deltoideus. The non-dominant arm was preferred.

Part C - C9: No Vaccination

Arm description

No vaccination was given to Part C - Cohort 9 participants within 3 months after Visit 1. After the 3-month follow-up period, participants in Cohort 9 were to be offered a BNT162b2 vaccination, depending on the epidemiological situation, local regulatory authority recommendations, and/or variant vaccine authorization status. 35 participants were randomized to Part C - Cohort 9. As per protocol, these participants did not receive treatment.

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 1	Part A - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - C7: 1 Dose of 30 μg BNT162b2 (B.1.1.529.1)	Part C - C8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - C9: No Vaccination
Started	21	20	20	20	42	17	349	352	361	72	71	35
Completed	14	10	15	12	29	13	280	291	299	60	55	30
Not completed	7	10	5	8	13	4	69	61	62	12	16	5
Adverse event, serious fatal	-	-	-	-	-	-	1	-	2	-	-	-
Consent withdrawn by subject	-	-	1	3	3	-	30	9	3	2	5	1
Physician decision	-	-	-	-	-	-	2	-	7	-	-	-
Lost to follow-up	2	4	2	3	5	2	15	12	38	6	6	-
Not further specified	1	-	-	-	-	-	1	-	2	1	-	1
Withdrawal by subject	2	3	2	2	4	2	4	22	8	1	3	2
Protocol deviation	2	3	-	-	1	-	16	18	2	2	2	1

Baseline characteristics

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Reporting group title

Part A - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Reporting group description

Participants in Part A - Cohort 1 received 1 dose of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection on Day 1

Reporting group title

Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Reporting group description

Participants in Part A - Cohort 2 received 2 doses of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection one on Day 1 and one on Day 56

Reporting group title

Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)

Reporting group description

Participants in Part A - Cohort 3 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.1.7) on Day 1

Reporting group title

Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)

Reporting group description

Participants in Part A - Cohort 4 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.617.2) on Day 1

Reporting group title

Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)

Reporting group description

Reporting group title

Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Reporting group description

Reporting group title

Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Reporting group description

Participants in Part B - Cohort 1 received 1 dose of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection on Day 1

Reporting group title

Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)

Reporting group description

Participants in Part B - Cohort 4 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.617.2) on Day 1

Reporting group title

Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Reporting group description

Reporting group title

Part C - C7: 1 Dose of 30 μg BNT162b2 (B.1.1.529.1)

Reporting group description

Participants in Part C - Cohort 7 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.1.529.1) on Day 1

Reporting group title

Part C - C8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)

Reporting group description

Participants in Part C - Cohort 8 received 1 dose of 30 μg BNT162b2 original vaccine on Day 1

Reporting group title

Part C - C9: No Vaccination

Reporting group description

Reporting group values	Part A - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - C7: 1 Dose of 30 μg BNT162b2 (B.1.1.529.1)	Part C - C8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - C9: No Vaccination	Total
Number of subjects	21	20	20	20	42	17	349	352	361	72	71	35	1380
Age categorical
Part A and B: Safety Set - All participants who received at least one dose in of IMP. 35 participants were randomized to Part C - Cohort 9 but, as per protocol, these participants did not receive treatment.
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	21	20	20	20	37	17	304	279	336	68	65	32	1219
From 65-84 years	0	0	0	0	5	0	45	73	25	4	5	3	160
85 years and over	0	0	0	0	0	0	0	0	0	0	1	0	1
Age continuous
Part A and B: Safety Set - All participants who received at least one dose in of IMP. 35 participants were randomized to Part C - Cohort 9 but, as per protocol, these participants did not receive treatment.
Units: years
arithmetic mean (standard deviation)	35.4 ( 11.13 )	38.7 ( 9.79 )	36.0 ( 11.89 )	39.8 ( 8.53 )	47.5 ( 11.10 )	37.1 ( 11.21 )	48.1 ( 14.68 )	50.5 ( 15.27 )	42.1 ( 15.91 )	41.9 ( 12.14 )	43.5 ( 13.57 )	44.5 ( 11.5 )	-
Gender categorical
Part A and B: Safety Set - All participants who received at least one dose in of IMP. 35 participants were randomized to Part C - Cohort 9 but, as per protocol, these participants did not receive treatment.
Units: Subjects
Female	11	12	10	13	14	11	169	161	204	42	43	25	715
Male	10	8	10	7	28	6	180	191	157	30	28	10	665
Race
Part A and B: Safety Set - All participants who received at least one dose in of IMP. 35 participants were randomized to Part C - Cohort 9 but, as per protocol, these participants did not receive treatment.
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	1	2	0	0	0	1	4
Asian	0	1	1	1	4	0	10	6	0	4	4	1	32
Native Hawaiian or Other Pacific Islander	1	1	0	0	0	0	0	0	0	0	0	0	2
Black or African American	0	0	0	0	3	6	50	8	242	4	7	2	322
White	20	18	19	19	35	11	258	330	15	62	59	31	877
Other	0	0	0	0	0	0	0	3	63	0	0	0	66
Multiracial	0	0	0	0	0	0	30	3	41	0	1	0	75
Not reported	0	0	0	0	0	0	0	0	0	1	0	0	1
Unknown	0	0	0	0	0	0	0	0	0	1	0	0	1
Region of Enrollment
Part A and B: Safety Set - All participants who received at least one dose in of IMP. 35 participants were randomized to Part C - Cohort 9 but, as per protocol, these participants did not receive treatment.
Units: Subjects
Turkey	0	0	0	0	0	0	137	0	0	0	0	0	137
United States	21	20	20	20	42	17	134	284	23	62	62	32	737
South Africa	0	0	0	0	0	0	78	4	338	0	0	0	420
Germany	0	0	0	0	0	0	0	64	0	10	9	3	86
Ethnicity
Part A and B: Safety Set - All participants who received at least one dose in of IMP. 35 participants were randomized to Part C - Cohort 9 but, as per protocol, these participants did not receive treatment.
Units: Subjects
Hispanic or Latino	7	3	9	1	5	5	30	55	10	12	5	5	147
Not Hispanic or Latino	14	17	11	19	37	12	317	294	348	59	66	30	1224
Not reported	0	0	0	0	0	0	2	2	0	0	0	0	4
Unknown	0	0	0	0	0	0	0	1	3	1	0	0	5
Body Mass Index (BMI)
Part A and B: Safety Set - All participants who received at least one dose in of IMP. 35 participants were randomized to Part C - Cohort 9 but, as per protocol, these participants did not receive treatment. Measure Analysis Population Description: Height was missing for 1 participant in Part A - Cohort 6 and BMI could therefore not be calculated
Units: kg/m^2
arithmetic mean (standard deviation)	27.54 ( 5.508 )	27.97 ( 6.840 )	30.09 ( 6.509 )	29.72 ( 6.287 )	29.83 ( 6.722 )	30.82 ( 8.394 )	28.29 ( 6.012 )	28.78 ( 6.202 )	26.30 ( 8.413 )	29.25 ( 6.648 )	28.60 ( 6.581 )	30.23 ( 5.133 )	-

End points

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Reporting group title

Part A - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Reporting group description

Participants in Part A - Cohort 1 received 1 dose of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection on Day 1

Reporting group title

Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Reporting group description

Participants in Part A - Cohort 2 received 2 doses of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection one on Day 1 and one on Day 56

Reporting group title

Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)

Reporting group description

Participants in Part A - Cohort 3 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.1.7) on Day 1

Reporting group title

Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)

Reporting group description

Participants in Part A - Cohort 4 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.617.2) on Day 1

Reporting group title

Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)

Reporting group description

Reporting group title

Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Reporting group description

Reporting group title

Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Reporting group description

Participants in Part B - Cohort 1 received 1 dose of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection on Day 1

Reporting group title

Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)

Reporting group description

Participants in Part B - Cohort 4 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.617.2) on Day 1

Reporting group title

Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Reporting group description

Reporting group title

Part C - C7: 1 Dose of 30 μg BNT162b2 (B.1.1.529.1)

Reporting group description

Participants in Part C - Cohort 7 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.1.529.1) on Day 1

Reporting group title

Part C - C8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)

Reporting group description

Participants in Part C - Cohort 8 received 1 dose of 30 μg BNT162b2 original vaccine on Day 1

Reporting group title

Part C - C9: No Vaccination

Reporting group description

Subject analysis set title

BNT162-17 Part B - C1 / C4591001

Subject analysis set type

Sub-group analysis

Subject analysis set description

BNT162-17 Part B - Cohort 1 participants received 1 dose of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection on Day 1 and C4591001 participants received 2 doses of BNT162b2 30 μg. To evaluate the primary immunogenicity endpoints for Part B Cohort 1, 4 and 6, separate control groups, one for each cohort in Part B, were selected from the C4591001 trial who received 2 doses of BNT162b2 and had corresponding immune results at 1 month post 2nd dose

Subject analysis set title

BNT162-17 Part B - C4 / C4591001

Subject analysis set type

Sub-group analysis

Subject analysis set description

BNT162-17 Part B - Cohort 4 participants received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.617.2) as a single injection on Day 1 and selected C4591001 participants received 2 doses of BNT162b2 30 μg. To evaluate the primary immunogenicity endpoints for Part B Cohort 1, 4 and 6, separate control groups, one for each cohort in Part B, were selected from the C4591001 trial who received 2 doses of BNT162b2 and had corresponding immune results at 1 month post 2nd dose.

Subject analysis set title

BNT162-17 Part B - C6 / C4591001

Subject analysis set type

Sub-group analysis

Subject analysis set description

BNT162-17 Part B - Cohort 6 participants received 3 doses of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), as a single injection one on Day 1, one on Day 21 and one approximately 6 months after the second dose. C4591001 participants received 2 doses of BNT162b2 30 μg. Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. This set included 275 participants from the Phase III trial C4591001.

Subject analysis set title

Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 / Cohort 8: 1 Dose

Subject analysis set type

Sub-group analysis

Subject analysis set description

Cohort 7 participants received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.1.529.1) on Day 1 and Cohort 8 participants received 1 dose of 30 μg BNT162b2 original vaccine on Day 1

Subject analysis set title

C4591001 BNT162b2 30 μg

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants had previously received two injections of 30 μg BNT162b2 at least 6 months after the second BNT162b2 dose.

Subject analysis set title

Part B - C6: BNT162b2 With Evidence of Prior Infection

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received 3 doses of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), as a single injection one on Day 1, one on Day 21 and one approximately 6 months after the second dose.

Subject analysis set title

Part B - C6: BNT162b2 Without Evidence of Infection

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received 3 doses of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), as a single injection one on Day 1, one on Day 21 and one approximately 6 months after the second dose.

Subject analysis set title

Part B - C1: BNT162b2 Without Evidence of Infection

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received 1 dose of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection on Day 1

Subject analysis set title

Part B - C6 With Prior Infection / C6 Without Prior Infection

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in Cohort 6 with or without evidence of prior infection received 3 doses of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), as a single injection one on Day 1, one on Day 21 and one approximately 6 months after the second dose.

Subject analysis set title

Part B - C6 With Prior Infection / C1 Without Prior Infection

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants in Cohort 6 with evidence of infection received 3 doses of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2), as a single injection one on Day 1, one on Day 21 and one approximately 6 months after the second dose. Participants in Cohort 1 without prior evidence of infection received 1 dose of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection on Day 1

Primary: All Parts - Percentage of Participants Reporting Local Reactions at the Injection Site (Pain, Tenderness, Erythema/ Redness, Induration/Swelling)

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End point title

All Parts - Percentage of Participants Reporting Local Reactions at the Injection Site (Pain, Tenderness, Erythema/ Redness, Induration/Swelling) ^[1]

End point description

Local reactions of any grade are reported. Local reactions were graded using criteria based on the FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments collected in the electronic diary (e-diary) or mapped from the adverse event case report form from Day 1 to Day 7 after each IMP dose. For Erythema/redness and Induration/swelling, the reported size had to be at least 2.5 cm to be deemed as a local reaction. Local reactions with a size less than 2.5 cm were not included in the analysis. Per protocol, participants in C9 did not receive a vaccination and were not included in this analysis. Reactogenicity set, i.e., all participants included in the Safety Set with any reactogenicity data reported after IMP injection.

End point type

Primary

End point timeframe

from Day 1 to Day 7 after each IMP dose

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

End point values	Part A - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - C7: 1 Dose of 30 μg BNT162b2 (B.1.1.529.1)	Part C - C8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - C9: No Vaccination
Number of subjects analysed	21	20	19	20	40	17	341	348	358	72	70	0 ^[2]
Units: Percentage of participants
number (not applicable)
Any local reaction - Overall	90.5	100	89.5	95.0	92.5	88.2	85.0	89.1	72.9	87.5	87.1
Pain at the injection site - Overall	81.0	95.0	73.7	85.0	67.5	76.5	74.5	75.9	69.0	79.2	74.3
Tenderness - Overall	85.7	100	89.5	90.0	82.5	82.4	64.5	78.4	56.1	76.4	80.0
Erythema/redness - Overall	4.8	15.0	5.3	5.0	20.0	5.9	10.0	8.6	13.1	15.3	10.0
Induration/swelling - Overall	4.8	15.0	5.3	10.0	25.0	23.5	10.6	8.6	16.2	11.1	7.1
Any local reaction - After IMP Dose 1	90.5	100	89.5	95.0	92.5	75.0	85.0	89.1	61.4	87.5	87.1
Pain at the injection site - After IMP Dose 1	81.0	95.0	73.7	85.0	67.5	62.5	74.5	75.9	55.9	79.2	74.3
Tenderness - After IMP Dose 1	85.7	100	89.5	90.0	82.5	75.0	64.5	78.4	38.3	76.4	80.0
Erythema/redness - After IMP Dose 1	4.8	15.0	5.3	5.0	20.0	6.3	10.0	8.6	6.3	15.3	10.0
Induration/swelling - After IMP Dose 1	4.8	15.0	5.3	10.0	25.0	12.5	10.6	8.6	10.4	11.1	7.1
Any local reaction - After IMP Dose 2	0	85.7	0	0	0	71.4	0	0	47.7	0	0
Pain at the injection site - After IMP Dose 2	0	78.6	0	0	0	64.3	0	0	44.2	0	0
Tenderness - After IMP Dose 2	0	64.3	0	0	0	71.4	0	0	24.9	0	0
Erythema/redness - After IMP Dose 2	0	0	0	0	0	0	0	0	5.0	0	0
Induration/swelling - After IMP Dose 2	0	7.1	0	0	0	0	0	0	6.9	0	0
Any local reaction - After IMP Dose 3	0	0	0	0	0	80.0	0	0	57.3	0	0
Pain at the injection site - After IMP Dose 3	0	0	0	0	0	80.0	0	0	51.9	0	0
Tenderness - After IMP Dose 3	0	0	0	0	0	70.0	0	0	41.7	0	0
Erythema/redness - After IMP Dose 3	0	0	0	0	0	0	0	0	6.4	0	0
Induration/swelling - After IMP Dose 3	0	0	0	0	0	30.0	0	0	6.4	0	0

Notes
[2] - As per protocol, these participants did not receive treatment and were therefore excluded

No statistical analyses for this end point

Primary: All Parts - Percentage of Participants Reporting Systemic Events (Fever, Fatigue, Headache, Chills, Vomiting, Nausea, Diarrhea, New or Worsened Muscle Pain, and New or Worsened Joint Pain)

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End point title

All Parts - Percentage of Participants Reporting Systemic Events (Fever, Fatigue, Headache, Chills, Vomiting, Nausea, Diarrhea, New or Worsened Muscle Pain, and New or Worsened Joint Pain) ^[3]

End point description

Systemic reactions of any grade are reported. Systemic reactions were graded using criteria based on the FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials"; the guidance uses the Grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening). The reporting of systemic reactions was based on the participant's assessments collected in the e-diary or mapped from the adverse event case report form from Day 1 to Day 7 after each IMP dose. For Fever, the reported oral temperature had to be ≥38.0°C to be deemed as a systemic event. Oral temperature less than 38.0°C was not included in the analysis. Per protocol, participants in C9 did not receive a vaccination and were not included in this analysis. Reactogenicity set, i.e., all participants included in the Safety Set with any reactogenicity data reported after IMP injection.

End point type

Primary

End point timeframe

from Day 1 to Day 7 after each IMP dose

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

End point values	Part A - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - C7: 1 Dose of 30 μg BNT162b2 (B.1.1.529.1)	Part C - C8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - C9: No Vaccination
Number of subjects analysed	21	20	19	20	40	17	341	347	358	72	70	0 ^[4]
Units: Percentage of participants
number (not applicable)
Any systemic event - Overall	81.0	100	78.9	80.0	82.5	76.5	74.8	76.9	70.7	72.2	78.6
Oral temperature of ≥ 38.0 °C – Overall	19.0	25.0	15.8	10.0	0	5.9	9.4	9.8	9.5	1.4	4.3
Nausea – Overall	9.5	45.0	21.1	35.0	10.0	23.5	17.9	18.4	26.0	12.5	21.4
Vomiting – Overall	0	15.0	0	5.0	0	5.9	2.3	2.0	9.5	1.4	0
Diarrhea – Overall	9.5	25.0	15.8	10.0	15.0	23.5	5.6	11.2	19.0	11.1	14.3
Headache – Overall	71.4	85.0	63.2	40.0	55.0	58.8	46.9	51.3	53.1	44.4	50.0
Fatigue – Overall	71.4	95.0	78.9	75.0	75.0	52.9	64.2	63.4	50.3	55.6	62.9
Chills – Overall	47.6	65.0	15.8	45.0	32.5	41.2	26.7	33.1	21.5	15.3	20.0
New or worsened muscle pain – Overall	47.6	70.0	52.6	40.0	40.0	47.1	36.1	37.8	39.9	27.8	27.1
New or worsened joint pain – Overall	28.6	35.0	21.1	20.0	32.5	29.4	25.5	22.5	28.2	12.5	12.9
Any systemic event – After IMP Dose 1	81.0	90.0	78.9	80.0	82.5	68.8	74.8	76.9	58.5	72.2	78.6
Oral temperature of ≥ 38.0 °C – After IMP Dose 1	19.0	20.0	15.8	10.0	0	0	9.4	9.8	4.0	1.4	4.3
Nausea – After IMP Dose 1	9.5	30.0	21.1	35.0	10.0	18.8	17.9	18.4	16.7	12.5	21.4
Vomiting – After IMP Dose 1	0	5.0	0	5.0	0	6.3	2.3	2.0	6.3	1.4	0
Diarrhea – After IMP Dose 1	9.5	20.0	15.8	10.0	15.0	12.5	5.6	11.2	12.7	11.1	14.3
Headache – After IMP Dose 1	71.4	80.0	63.2	40.0	55.0	50.0	46.9	51.3	36.0	44.4	50.0
Fatigue – After IMP Dose 1	71.4	85.0	78.9	75.0	75.0	50.0	64.2	63.4	34.3	55.6	62.9
Chills – After IMP Dose 1	47.6	45.0	15.8	45.0	32.5	18.8	26.7	33.1	12.4	15.3	20.0
New or worsened muscle pain – After IMP Dose 1	47.6	60.0	52.6	40.0	40.0	37.5	36.1	37.8	26.5	27.8	27.1
New or worsened joint pain – After IMP Dose 1	28.6	30.0	21.1	20.0	32.5	18.8	25.5	22.5	19.6	12.5	12.9
Any systemic event – After IMP Dose 2	0	93.3	0	0	0	60.0	0	0	43.0	0	0
Oral temperature of ≥ 38.0 °C – After IMP Dose 2	0	6.7	0	0	0	6.7	0	0	3.7	0	0
Nausea – After IMP Dose 2	0	33.3	0	0	0	13.3	0	0	8.7	0	0
Vomiting – After IMP Dose 2	0	13.3	0	0	0	6.7	0	0	2.8	0	0
Diarrhea – After IMP Dose 2	0	13.3	0	0	0	13.3	0	0	6.2	0	0
Headache – After IMP Dose 2	0	73.3	0	0	0	40.0	0	0	27.2	0	0
Fatigue – After IMP Dose 2	0	86.7	0	0	0	40.0	0	0	23.8	0	0
Chills – After IMP Dose 2	0	40.0	0	0	0	20.0	0	0	9.0	0	0
New or worsened muscle pain – After IMP Dose 2	0	60.0	0	0	0	26.7	0	0	18.9	0	0
New or worsened joint pain – After IMP Dose 2	0	20.0	0	0	0	26.7	0	0	12.1	0	0
Any systemic event – After IMP Dose 3	0	0	0	0	0	60.0	0	0	48.1	0	0
Oral temperature of ≥ 38.0 °C – After IMP Dose 3	0	0	0	0	0	0	0	0	4.4	0	0
Nausea – After IMP Dose 3	0	0	0	0	0	10.0	0	0	11.2	0	0
Vomiting – After IMP Dose 3	0	0	0	0	0	0	0	0	4.1	0	0
Diarrhea – After IMP Dose 3	0	0	0	0	0	10.0	0	0	7.5	0	0
Headache – After IMP Dose 3	0	0	0	0	0	40.0	0	0	35.3	0	0
Fatigue – After IMP Dose 3	0	0	0	0	0	40.0	0	0	29.5	0	0
Chills – After IMP Dose 3	0	0	0	0	0	20.0	0	0	9.2	0	0
New or worsened muscle pain – After IMP Dose 3	0	0	0	0	0	40.0	0	0	18.3	0	0
New or worsened joint pain – After IMP Dose 3	0	0	0	0	0	20.0	0	0	9.5	0	0

Notes
[4] - As per protocol, these participants did not receive treatment and were therefore excluded

No statistical analyses for this end point

Primary: All Parts - Percentage of Participants Reporting Adverse Events (AEs)

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End point title

All Parts - Percentage of Participants Reporting Adverse Events (AEs) ^[5]

End point description

An AE is defined as TEAE if the event onset date and time is after the first IMP dose (if the event was absent before the first administration of the IMP) or worsened after the first IMP dose (if the event was present before the first administration of the IMP). In the event of an incomplete onset date, the event was considered as treatment-emergent unless the partial onset date information or complete or partial end date confirmed the onset date or the event end prior to the first dose of IMP. Percentages for dose 1, 2, 3 and overall summaries are based upon the number of participants who received the respective IMP dose. Safety set, i.e., all participants who received at least 1 dose of IMP. 21 participants assigned to Part B C4 actually received BNT162b2 (treatment of Part A C5) and therefore were included in the analyses of safety set of Part A C5 and excluded from Part B safety set. 1 participant from Part A C6 also received BNT162b2 and was included in the Part A C5 safety set.

End point type

Primary

End point timeframe

Dose 1 up to 1 month after each dose (all parts)

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

End point values	Part A - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - C7: 1 Dose of 30 μg BNT162b2 (B.1.1.529.1)	Part C - C8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - C9: No Vaccination
Number of subjects analysed	21	20	20	20	42	17	349	352	361	72	71	0 ^[6]
Units: Percentage of participants
number (not applicable)
Any AE after IMP Dose 1	19.0	30.0	30.0	15.0	66.7	29.4	14.6	13.1	20.2	12.5	19.7
Any AE after IMP Dose 2	0	27.8	0	0	0	17.6	0	0	15.7	0	0
Any AE after IMP Dose 3	0	0	0	0	0	20.0	0	0	15.2	0	0

Notes
[6] - As per protocol, these participants did not receive treatment and were therefore excluded

No statistical analyses for this end point

Primary: All Parts - Percentage of Participants Reporting Serious Adverse Events (SAEs)

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End point title

All Parts - Percentage of Participants Reporting Serious Adverse Events (SAEs) ^[7]

End point description

An SAE was any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/ incapacity; was a congenital anomaly/birth defect and/or was another important medical event. SAEs from dose 1 up to 6 months post last IMP dose are presented. MedDRA (version 26.1) coding dictionary applied. An SAE was defined as TESAE if the event onset date and time was after the first IMP dose (if the event was absent before the first administration of the IMP) or worsened after the first IMP dose (if the event was present before the first administration of the IMP). In the event of an incomplete onset date, the event was considered as treatment-emergent unless the partial onset date information or complete or partial end date confirmed the onset date or the event end prior to the first dose of IMP. Safety set.

End point type

Primary

End point timeframe

Dose 1 up to 6 months after the last dose

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

End point values	Part A - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - C7: 1 Dose of 30 μg BNT162b2 (B.1.1.529.1)	Part C - C8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - C9: No Vaccination
Number of subjects analysed	21	20	20	20	42	17	349	352	361	72	71	0 ^[8]
Units: Percentage of participants
number (not applicable)
Percentage of Participants Reporting SAEs	0	0	0	0	0	0	1.1	1.7	3.6	0	7.0

Notes
[8] - As per protocol, these participants did not receive treatment and were therefore excluded

No statistical analyses for this end point

Primary: Part B - GMR of B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (2020-002641-42) Trial

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End point title

Part B - GMR of B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (2020-002641-42) Trial ^[9]

End point description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and vaccine group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.1.7 and reference strain respectively at the given dose/sampling time point within the specified window. Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. GMR = Geometric mean ratio; NT = neutralizing titers

End point type

Primary

End point timeframe

1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (2020-002641-42) trial

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

End point values	BNT162-17 Part B - C1 / C4591001
Number of subjects analysed	631 ^[10]
Units: Titer ratio
geometric mean (confidence interval 95%)	8.81 (7.49 to 10.36)

Notes
[10] - Includes 299 participants from BNT162-17 and 332 participants from C4591001 (2020-002641-42).

No statistical analyses for this end point

Primary: Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

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End point title

Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial ^[11]

End point description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of least square means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. The overall number of participants analyzed represents the number of participants with valid and determinate assay results for B.1.617.2 and reference strain respectively at the given dose/sampling time point within the specified window. Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. GMR = Geometric mean ratio; NT = neutralizing titers

End point type

Primary

End point timeframe

1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (EudraCT number: 2020-002641-42) trial

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

End point values	BNT162-17 Part B - C1 / C4591001
Number of subjects analysed	631 ^[12]
Units: Titer ratio
geometric mean (confidence interval 95%)	4.88 (4.19 to 5.68)

Notes
[12] - Includes 299 participants from BNT162-17 and 332 participants from C4591001 (2020-002641-42).

No statistical analyses for this end point

Primary: Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

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End point title

Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial ^[13]

End point description

End point type

Primary

End point timeframe

1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (2020-002641-42) trial

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

End point values	BNT162-17 Part B - C4 / C4591001
Number of subjects analysed	637 ^[14]
Units: Titer ratio
geometric mean (confidence interval 95%)	6.40 (5.47 to 7.48)

Notes
[14] - Includes 317 participants from BNT162-17 and 320 participants from C4591001 (2020-002641-42).

No statistical analyses for this end point

Primary: Part B - Difference in Seroresponse (SR) to B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001

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End point title

Part B - Difference in Seroresponse (SR) to B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 ^[15]

End point description

Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For subjects with a baseline titer less than the lower limit of quantitation (<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Immunogenicity Analysis Set.

End point type

Primary

End point timeframe

1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (2020-002641-42) trial

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: No statistical analysis was planned for this endpoint.

End point values	BNT162-17 Part B - C1 / C4591001
Number of subjects analysed	630 ^[16]
Units: Percentage difference
number (confidence interval 95%)	0.25 (-4.86 to 5.26)

Notes
[16] - Includes 298 participants from BNT162-17 and 332 participants from C4591001 (2020-002641-42).

No statistical analyses for this end point

Primary: Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2- experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001

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End point title

Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2- experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 ^[17]

End point description

End point type

Primary

End point timeframe

1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (2020-002641-42) trial

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

End point values	BNT162-17 Part B - C1 / C4591001
Number of subjects analysed	630 ^[18]
Units: Percentage difference
number (confidence interval 95%)	-2.39 (-7.74 to 2.84)

Notes
[18] - Includes 298 participants from BNT162-17 and 332 participants from C4591001 (2020-002641-42).

No statistical analyses for this end point

Primary: Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (2020-002641-42)

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End point title

Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (2020-002641-42) ^[19]

End point description

End point type

Primary

End point timeframe

1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 trial

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

End point values	BNT162-17 Part B - C4 / C4591001
Number of subjects analysed	633 ^[20]
Units: Percentage difference
number (confidence interval 95%)	9.70 (5.68 to 13.97)

Notes
[20] - Includes 313 participants from BNT162-17 and 320 participants from C4591001 (2020-002641-42).

No statistical analyses for this end point

Primary: Part B - GMR of B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

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End point title

Part B - GMR of B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial ^[21]

End point description

In COVID-19 vaccine naïve individuals (Cohort B6) the aim was to generate data to support a 2-dose primary regimen of alpha-delta multivalent BNT162b2 vaccine in SARS-CoV-2 naïve, unvaccinated individuals. The population recruited in Cohort B6, while complying with the inclusion criterium of no known history SARS-CoV-2 infection, were retrospectively seropositive for SARS-CoV-2 by planned N-binding antibody assessment at baseline. While the cohort was COVID-19 vaccine-naïve, it was not SARS-CoV-2-naïve as needed to match the control population (C4591001). Procedurally, submission of a protocol amendment was not possible as the end of trial notification had been submitted in one country. However, the Statistical Analysis Plan was amended to describe that data analysis for the original primary immunogenicity endpoints for Cohort B6 could not be performed according to the protocol. Samples taken in Cohort B6 were used to address other primary, secondary and exploratory endpoints.

End point type

Primary

End point timeframe

1 month

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

End point values	BNT162-17 Part B - C6 / C4591001
Number of subjects analysed	0 ^[22]
Units: Titer ratio
geometric mean (confidence interval 95%)	( to )

Notes
[22] - Data could not be collected as participants were not SARS-CoV-2 naïve

No statistical analyses for this end point

Primary: Part B - GMR of B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

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End point title

Part B - GMR of B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial ^[23] ^[24]

End point description

End point type

Primary

End point timeframe

1 month

Notes
[23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint.
[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: This endpoint was meant to report only data relevant to Part B (Cohorts 1, 4, and 6). However, this data is not available for these cohorts.

End point values	Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)
Number of subjects analysed	0 ^[25]	0 ^[26]	0 ^[27]
Units: Titer ratio
geometric mean (confidence interval 95%)	( to )	( to )	( to )

Notes
[25] - Data could not be collected as participants were not SARS-CoV-2 naïve
[26] - Data could not be collected as participants were not SARS-CoV-2 naïve
[27] - Data could not be collected as participants were not SARS-CoV-2 naïve

No statistical analyses for this end point

Primary: Part B - The Difference in SR to B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

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End point title

Part B - The Difference in SR to B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial ^[28] ^[29]

End point description

End point type

Primary

End point timeframe

1 month

Notes
[28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint.
[29] - 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: This endpoint was meant to report only data relevant to Part B (Cohorts 1 and 6). However, this data is not available for these cohorts.

End point values	Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)
Number of subjects analysed	0 ^[30]	0 ^[31]
Units: Percentage difference
number (confidence interval 95%)	( to )	( to )

Notes
[30] - Data could not be collected as participants were not SARS-CoV-2 naïve
[31] - Data could not be collected as participants were not SARS-CoV-2 naïve

No statistical analyses for this end point

Primary: Part B - The Difference in SR to B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

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End point title

Part B - The Difference in SR to B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial ^[32] ^[33]

End point description

End point type

Primary

End point timeframe

1 month

Notes
[32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint.
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was meant to report only data relevant to Part B (Cohorts 1, 4, and 6). However, this data is not available for these cohorts.

End point values	Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)
Number of subjects analysed	0 ^[34]	0 ^[35]	0 ^[36]
Units: Percentage difference
number (confidence interval 95%)	( to )	( to )	( to )

Notes
[34] - Data could not be collected as participants were not SARS-CoV-2 naïve
[35] - Data could not be collected as participants were not SARS-CoV-2 naïve
[36] - Data could not be collected as participants were not SARS-CoV-2 naïve

No statistical analyses for this end point

Primary: Part B - GMR of Reference Strain NT After One Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in Participants With Evidence of Prior Infection to the Reference Strain NT After 2 Doses of BNT162b2 in Participants Without Evidence of Infection

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End point title

Part B - GMR of Reference Strain NT After One Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in Participants With Evidence of Prior Infection to the Reference Strain NT After 2 Doses of BNT162b2 in Participants Without Evidence of Infection ^[37]

End point description

GMR of reference strain NT 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection and to the reference strain NT 1 month after two doses of BNT162b2 in participants without evidence of infection (COVID-19 Vaccine-naïve Participants) from the Phase III trial C4591001. GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of LS means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. Assay results below the LLOQ were set to 0.5 × LLOQ. Immunogenicity Analysis Set.

End point type

Primary

End point timeframe

3 weeks post Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 trial

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: No statistical analysis was planned for this endpoint.

End point values	BNT162-17 Part B - C6 / C4591001
Number of subjects analysed	537 ^[38]
Units: Titer ratio
geometric mean (confidence interval 95%)	13.12 (11.14 to 15.45)

Notes
[38] - Includes 262 participants from BNT162-17 and 275 participants from C4591001 (2020-002641-42).

No statistical analyses for this end point

Primary: Part B - The Difference in SRs to the Reference Strain NT in Participants With Evidence of Prior Infection and to the Reference Strain NT in Participants Without Evidence of Infection (COVID-19 Vaccine-naïve Participants)

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End point title

Part B - The Difference in SRs to the Reference Strain NT in Participants With Evidence of Prior Infection and to the Reference Strain NT in Participants Without Evidence of Infection (COVID-19 Vaccine-naïve Participants) ^[39]

End point description

The difference in SRs to the reference strain NT 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection to the reference strain NT 1 month after two doses of BNT162b2 in participants without evidence of infection (COVID-19 Vaccine-naïve Participants) from the Phase III trial C4591001. Seroresponse was defined as achieving a ≥4-fold rise from baseline. If the baseline measurement was below the LLOQ, a post-vaccination assay result ≥4 × LLOQ was considered a seroresponse. Adjusted difference in proportions was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage 2-Sided CI based on the Newcombe method with minimum risk weights for the difference in proportions. Immunogenicity Analysis Set.

End point type

Primary

End point timeframe

3 weeks post Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 trial

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: No statistical analysis was planned for this endpoint.

End point values	BNT162-17 Part B - C6 / C4591001
Number of subjects analysed	535 ^[40]
Units: Percentage difference
number (confidence interval 95%)	-4.55 (-10.04 to 0.83)

Notes
[40] - Includes 260 participants from BNT162-17 and 275 participants from C4591001 (2020-002641-42).

No statistical analyses for this end point

Primary: Part C - GMR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 and 8

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End point title

Part C - GMR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 and 8 ^[41]

End point description

End point type

Primary

End point timeframe

1 month after 1 dose of BNT162b2 or BNT162b2 (B.1.1.529.1)

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

End point values	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 / Cohort 8: 1 Dose
Number of subjects analysed	121 ^[42]
Units: Titer ratio
geometric mean (confidence interval 95%)	0.94 (0.61 to 1.44)

Notes
[42] - Includes 64 participants from Cohort 7 and 57 participants from Cohort 8.

No statistical analyses for this end point

Primary: Part C - The Difference in SR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 & 8

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End point title

Part C - The Difference in SR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 & 8 ^[43]

End point description

Seroresponse was defined as a ≥4-fold rise in neutralizing titer from baseline. For participants with a baseline titer less than the lower limit of quantitation (<LLOQ), seroresponse was defined as a post-vaccination titer of ≥4× LLOQ. Adjusted difference was estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. Associated 2-sided 95% CI based on the Newcombe method with minimum risk weights for the difference in proportions. Immunogenicity Analysis Set.

End point type

Primary

End point timeframe

1 month after 1 dose of BNT162b2 or BNT162b2 (B.1.1.529.1)

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

End point values	Part C - Cohort 7: 1 Dose of 30 μg BNT162b2 / Cohort 8: 1 Dose
Number of subjects analysed	121 ^[44]
Units: Percentage difference
number (confidence interval 95%)	36.73 (19.21 to 51.17)

Notes
[44] - 64 participants from Cohort 7 and 57 participants from Cohort 8.

No statistical analyses for this end point

Secondary: Part A - Geometric Mean Titer (GMT) at Each Timepoint

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End point title

Part A - Geometric Mean Titer (GMT) at Each Timepoint ^[45]

End point description

GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ and above the ULOQ were set to ULOQ. Immunogenicity Analysis Set, i.e., all eligible randomized/assigned participants who received the trial intervention to which they were randomized or assigned, had a valid and determinate immunogenicity result from the blood sample collected within an appropriate window, and had no other important protocol deviations that could confound immunogenicity data. 999 = not applicable since Cohorts 1, 3, 4 and 5 received only 1 dose of IMP. 9999 = not applicable since Cohort 2 received dose 2 on Day 56 and did not receive dose 3. 99999 = not applicable since Cohort 6 received dose 2 on Day 21 and received dose 3 approximately 6 months after dose 2.

End point type

Secondary

End point timeframe

Day 1 up to Day 421

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: This endpoint only reports data for Part A (Cohorts 1-6).

End point values	Part A - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)
Number of subjects analysed	21	20	20	20	20	17
Units: Titer
geometric mean (confidence interval 95%)
Pre IMP dose 1 - B.1.1.7	18.9 (9.0 to 39.7)	26.9 (14.5 to 49.9)	17.4 (9.0 to 33.8)	48.4 (20.0 to 117.0)	9.6 (5.2 to 17.8)	6.9 (4.6 to 10.5)
1-week post IMP dose 1 - B.1.1.7	1403.9 (817.9 to 2409.8)	1340.5 (731.0 to 2458.2)	1090.8 (701.7 to 1695.5)	557.2 (365.4 to 849.4)	307.9 (209.1 to 453.5)	30.2 (6.8 to 133.1)
3-weeks post IMP dose 1 - B.1.1.7	1035.7 (659.9 to 1625.5)	1168.4 (756.8 to 1803.9)	956.0 (657.3 to 1390.4)	493.5 (365.0 to 667.3)	361.6 (223.9 to 584.2)	99999 (99999 to 99999)
1-month post IMP dose 1 - B.1.1.7	942.8 (552.6 to 1608.3)	1004.3 (705.3 to 1430.0)	1009.8 (697.8 to 1461.3)	468.5 (308.6 to 711.2)	314.5 (182.7 to 541.3)	99999 (99999 to 99999)
6-months post IMP dose 1 - B.1.1.7	156.6 (62.5 to 392.2)	9999 (9999 to 9999)	352.3 (192.4 to 645.3)	151.5 (68.9 to 333.1)	85.7 (36.9 to 199.3)	99999 (99999 to 99999)
12-months post IMP dose 1 - B.1.1.7	658.8 (385.8 to 1124.7)	9999 (9999 to 9999)	463.9 (180.0 to 1195.5)	241.0 (95.1 to 611.0)	463.9 (188.0 to 1144.8)	99999 (99999 to 99999)
Pre IMP dose 2 - B.1.1.7	999 (999 to 999)	151.0 (49.1 to 464.5)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	42.7 (12.5 to 145.9)
1-week post IMP dose 2 - B.1.1.7	999 (999 to 999)	987.0 (495.9 to 1964.4)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	207.5 (104.3 to 413.0)
1-month post IMP dose 2 - B.1.1.7	999 (999 to 999)	958.9 (586.3 to 1568.3)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	216.1 (101.7 to 459.0)
6-months post IMP dose 2 - B.1.1.7	999 (999 to 999)	349.0 (166.5 to 731.6)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	99999 (99999 to 99999)
12-months post IMP dose 2 - B.1.1.7	999 (999 to 999)	940.6 (480.4 to 1841.7)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	99999 (99999 to 99999)
6-months post IMP dose 2+pre IMP dose 3 - B.1.1.7	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	68.3 (21.7 to 215.2)
1-week post IMP dose 3 - B.1.1.7	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	640.0 (379.2 to 1080.2)
1-month post IMP dose 3 - B.1.1.7	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	562.0 (190.2 to 1660.6)
12-months post IMP dose 2 + 6-months post IMP dose	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	351.7 (162.4 to 761.8)
Pre IMP dose 1 - B.1.617.2	9.0 (4.8 to 16.7)	8.7 (5.1 to 15.0)	12.1 (6.4 to 22.8)	8.7 (6.0 to 12.6)	9.0 (5.2 to 15.8)	6.5 (4.7 to 9.0)
1-week post IMP dose 1 - B.1.617.2	526.6 (305.8 to 906.9)	385.0 (255.6 to 579.8)	517.1 (330.1 to 809.9)	359.2 (237.3 to 543.7)	254 (162.5 to 369.9)	27.7 (6.6 to 115.4)
3-weeks post IMP dose 1 - B.1.617.2	425.5 (283.1 to 723.5)	384.0 (251.0 to 587.6)	533.3 (368.0 to 772.7)	380.5 (265.8 to 544.8)	221.7 (123.0 to 399.6)	99999 (99999 to 99999)
1-month post IMP dose 1 - B.1.617.2	369.1 (209.3 to 650.8)	303.8 (199.2 to 463.2)	486.8 (349.2 to 678.6)	288.4 (199.5 to 417.0)	207.5 (126.3 to 340.8)	99999 (99999 to 99999)
6-months post IMP dose 1 - B.1.617.2	137.5 (51.6 to 366.1)	9999 (9999 to 9999)	217.7 (127.9 to 370.5)	123.9 (55.3 to 277.7)	35.6 (17.5 to 72.7)	99999 (99999 to 99999)
12-months post IMP dose 1 - B.1.617.2	640.0 (293.4 to 1396.1)	9999 (9999 to 9999)	199.9 (87.3 to 458.1)	212.5 (78.3 to 576.2)	226.3 (92.5 to 553.7)	99999 (99999 to 99999)
Pre IMP dose 2 - B.1.617.2	999 (999 to 999)	235.2 (144.0 to 384.1)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	60.4 (18.3 to 199.5)
1-week post IMP dose 2 - B.1.617.2	999 (999 to 999)	515.4 (342.7 to 774.9)	999 (999 to 999)	999 (999 to 999)	999 (99 to 999)	216.7 (134.6 to 348.7)
1-month post IMP dose 2 - B.1.617.2	999 (999 to 999)	517.8 (366.6 to 731.5)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	320.0 (139.1 to 736.4)
6-months post IMP dose 2 - B.1.617.2	999 (999 to 999)	226.3 (114.9 to 445.6)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	99999 (99999 to 99999)
12-months post IMP dose 2 - B.1.617.2	999 (999 to 999)	508.0 (288.7 to 893.9)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	99999 (99999 to 99999)
6-months post IMP dose 2+preIMP dose 3 - B.1.617.2	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	87.9 (26.2 to 294.9)
1-week post IMP dose 3 - B.1.617.2	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	819.8 (353.1 to 1903.2)
1-month post IMP dose 3 - B.1.617.2	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	640.0 (207.3 to 1976.3)
12-mths post dose 2+6-mths post dose 3 – B.1.617.2	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	424.9 (213.3 to 846.5)
Pre IMP dose 1 - Ref	14.9 (8.5 to 26.2)	18.7 (10.4 to 33.4)	18.3 (10.1 to 33.3)	27.8 (16.6 to 46.5)	14.1 (7.9 to 25.3)	6.8 (4.6 to 9.9)
1-week post IMP dose 1 - Ref	812.2 (474.1 to 1391.3)	519.8 (321.6 to 840.2)	640.0 (417.4 to 981.4)	702.0 (432.7 to 1138.7)	352.3 (238.3 to 521.0)	25.4 (6.6 to 97.7)
3-weeks post IMP dose 1 - Ref	678.1 (406.0 to 1132.3)	584.2 (357.5 to 954.8)	740.6 (495.0 to 1107.8)	748.0 (500.2 to 1118.6)	408.7 (262.0 to 637.4)	99999 (99999 to 99999)
1-month post IMP dose 1 - Ref	589.9 (376.9 to 923.1)	452.5 (283.5 to 722.4)	688.4 (467.0 to 1014.9)	748.0 (469.3 to 1192.3)	380.5 (232.0 to 624.3)	99999 (99999 to 99999)
6-months post IMP dose 1 - Ref	163.5 (72.7 to 367.7)	9999 (9999 to 9999)	244.4 (143.8 to 415.4)	101.4 (57.8 to 178.0)	78.2 (42.2 to 145.0)	99999 (99999 to 99999)
12-months post IMP dose 1 - Ref	604.1 (311.3 to 1172.0)	9999 (9999 to 9999)	380.5 (164.8 to 878.9)	170.4 (67.6 to 429.5)	565.5 (244.1 to 1310.2)	99999 (99999 to 99999)
Pre IMP dose 2 - Ref	999 (999 to 999)	387.9 (227.7 to 660.9)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	37.5 (11.3 to 124.6)
1-week post IMP dose 2 - Ref	999 (999 to 999)	697.9 (453.5 to 1074.1)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	95.1 (59.8 to 151.4)
1-month post IMP dose 2 - Ref	999 (999 to 999)	665.1 (400.1 to 1105.6)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	136.1 (58.1 to 319.0)
6-months post IMP dose 2 - Ref	999 (999 to 999)	334.2 (171.5 to 651.2)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	99999 (99999 to 99999)
12-months post IMP dose 2 - Ref	999 (999 to 999)	527.9 (263.8 to 1056.2)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	99999 (99999 to 99999)
6-months post IMP dose 2+pre IMP dose 3 - Ref	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	53.1 (16.4 to 172.4)
1-week post IMP dose 3 - Ref	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	551.7 (299.8 to 1015.1)
1-month post IMP dose 3 - Ref	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	493.5 (195.5 to 1245.8)
12-mths post dose 2+6-mths post dose 3 – Ref	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	205.9 (80.1 to 528.8)

No statistical analyses for this end point

Secondary: Part A - Geometric Mean Fold Rises (GMFR) From Before Vaccination to Each Subsequent Time Point After Vaccination

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End point title

Part A - Geometric Mean Fold Rises (GMFR) From Before Vaccination to Each Subsequent Time Point After Vaccination ^[46]

End point description

GMFR is calculated as the mean of the difference of logarithmically transformed neutralization titers or antibody levels (later result minus earlier result) and exponentiating the mean. The associated 2-sided 95% CIs are obtained by constructing CIs using Student’s t-distribution for the mean difference on the natural log scale and exponentiating the confidence limits. Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ. Immunogenicity Analysis Set. 999 = not applicable since Cohorts 1, 3, 4 and 5 received only 1 dose of IMP. 9999 = not applicable since Cohort 2 received dose 2 on Day 56 and did not receive dose 3. 99999 = not applicable since Cohort 6 received dose 2 on Day 21 and received dose 3 approximately 6 months after dose 2.

End point type

Secondary

End point timeframe

Day 1 to Day 421

Notes
[46] - 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: This endpoint only reports data for Part A (Cohorts 1-6).

End point values	Part A - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)
Number of subjects analysed	21	20	20	20	20	17
Units: Fold rise
geometric mean (confidence interval 95%)
1-week post IMP dose 1 - B.1.1.7	68.6 (30.4 to 155.0)	78.8 (38.9 to 159.7)	95.5 (72.0 to 126.5)	13.0 (5.8 to 28.9)	31.4 (19.1 to 51.4)	4.8 (1.2 to 18.9)
3-weeks post IMP dose 1 - B.1.1.7	52.8 (28.4 to 98.2)	39.8 (23.3 to 68.0)	51.4 (30.3 to 87.3)	10.2 (4.8 to 21.9)	35.7 (20.6 to 61.6)	99999 (99999 to 99999)
1-month post IMP dose 1 - B.1.1.7	48.1 (24.8 to 93.2)	37.4 (22.8 to 61.4)	54.3 (31.9 to 92.5)	9.7 (3.8 to 24.8)	27.7 (14.0 to 55.2)	99999 (99999 to 99999)
6-months post IMP dose 1 - B.1.1.7	7.2 (2.9 to 18.0)	9999 (9999 to 9999)	18.7 (8.2 to 42.5)	2.9 (0.9 to 9.6)	9.0 (3.7 to 22.0)	99999 (99999 to 99999)
12-months post IMP dose 1 - B.1.1.7	21.1 (4.6 to 96.4)	9999 (9999 to 9999)	20.5 (6.2 to 68.2)	4.0 (0.5 to 33.3)	36.3 (13.8 to 95.5)	99999 (99999 to 99999)
Pre IMP dose 2 - B.1.1.7	999 (999 to 999)	6.2 (2.4 to 15.9)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	6.2 (2.2 to 17.4)
1-week post IMP dose 2 - B.1.1.7	999 (999 to 999)	64.0 (37.4 to 109.4)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	41.5 (20.9 to 82.6)
1-month post IMP dose 2 - B.1.1.7	999 (999 to 999)	39.5 (22.2 to 70.6)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	33.6 (17.9 to 63.3)
6-months post IMP dose 2 - B.1.1.7	999 (999 to 999)	15.7 (7.4 to 33.2)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	99999 (99999 to 99999)
12-months post IMP dose 2 - B.1.1.7	999 (999 to 999)	22.6 (6.7 to 76.7)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	99999 (99999 to 99999)
6-months post IMP dose 2+pre IMP dose 3 - B.1.1.7	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	12.4 (4.3 to 35.8)
1-week post IMP dose 3 - B.1.1.7	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	105.0 (76.8 to 143.6)
1-month post IMP dose 3 - B.1.1.7	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	82.0 (32.1 to 209.5)
12-mths post dose 2+6-mths post dose 3 – B.1.1.7	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	53.8 (25.6 to 113.0)
1-week post IMP dose 1 - B.1.617.2	52.7 (28.1 to 98.8)	64.0 (43.6 to 93.9)	73.1 (51.1 to 104.6)	35.9 (21.7 to 59.6)	27.2 (16.3 to 45.4)	4.9 (1.2 to 19.5)
3-weeks post IMP dose 1 - B.1.617.2	48.9 (28.4 to 84.2)	42.8 (27.6 to 66.5)	42.1 (26.2 to 67.6)	43.7 (27.1 to 70.6)	22.6 (12.3 to 41.7)	99999 (99999 to 99999)
1-month post IMP dose 1 - B.1.617.2	40.9 (23.4 to 71.5)	34.9 (23.5 to 51.7)	38.4 (22.1 to 66.7)	33.1 (22.4 to 49.1)	20.0 (11.7 to 34.2)	99999 (99999 to 99999)
6-months post IMP dose 1 - B.1.617.2	13.8 (5.3 to 35.6)	9999 (9999 to 9999)	16.3 (8.1 to 32.9)	14.3 (5.8 to 35.4)	4.4 (1.9 to 9.9)	99999 (99999 to 99999)
12-months post IMP dose 1 - B.1.617.2	42.2 (10.5 to 169.8)	9999 (9999 to 9999)	12.8 (4.4 to 37.4)	21.9 (5.2 to 93.3)	19.3 (6.9 to 54.0)	99999 (99999 to 99999)
Pre IMP dose 2 - B.1.617.2	999 (999 to 999)	27.4 (16.8 to 44.7)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	9.3 (3.2 to 27.5)
1-week post IMP dose 2 - B.1.617.2	999 (999 to 999)	86.7 (53.9 to 139.5)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	43.3 (26.9 to 69.7)
1-month post IMP dose 2 - B.1.617.2	999 (999 to 999)	60.4 (32.9 to 110.8)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	55.2 (24.0 to 126.9)
6-months post IMP dose 2 - B.1.617.2	999 (999 to 999)	26.9 (11.7 to 62.0)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	99999 (99999 to 99999)
12-months post IMP dose 2 - B.1.617.2	999 (999 to 999)	34.6 (8.1 to 146.7)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	99999 (99999 to 99999)
6-months post IMP dose 2+preIMP dose 3 - B.1.617.2	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	16.5 (5.0 to 54.5)
1-week post IMP dose 3 - B.1.617.2	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	121.8 (63.4 to 233.9)
1-month post IMP dose 3 - B.1.617.2	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	86.1 (28.2 to 263.2)
12-mths post dose 2+6-mths post dose 3 - B.1.617.2	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	61.8 (30.8 to 124.0)
1-week post IMP dose 1 - Ref	52.7 (33.3 to 83.2)	39.4 (21.6 to 71.9)	50.3 (38.7 to 65.4)	20.6 (11.0 to 38.7)	23.1 (15.8 to 33.8)	4.1 (1.3 to 13.3)
3-weeks post IMP dose 1 - Ref	46.1 (28.1 to 75.8)	29.2 (18.3 to 46.7)	37.7 (22.0 to 64.8)	26.9 (15.6 to 46.3)	26.3 (16.5 to 42.0)	99999 (99999 to 99999)
1-month post IMP dose 1 - Ref	40.9 (26.8 to 62.3)	24.3 (15.0 to 39.1)	36.4 (20.8 to 63.7)	26.9 (15.9 to 45.6)	23.1 (14.7 to 36.3)	99999 (99999 to 99999)
6-months post IMP dose 1 - Ref	10.5 (5.1 to 21.5)	9999 (9999 to 9999)	12.5 (6.1 to 25.4)	3.7 (1.8 to 7.5)	5.2 (2.9 to 9.2)	99999 (99999 to 99999)
12-months post IMP dose 1 - Ref	29.9 (9.2 to 97.1)	9999 (9999 to 9999)	17.7 (6.6 to 47.4)	6.0 (1.4 to 25.1)	26.5 (11.1 to 63.4)	99999 (99999 to 99999)
Pre IMP dose 2 - Ref	999 (999 to 999)	21.8 (12.8 to 37.2)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	5.5 (2.0 to 15.1)
1-week post IMP dose 2 - Ref	999 (999 to 999)	66.8 (27.7 to 161.5)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	19.0 (12.0 to 30.3)
1-month post IMP dose 2 - Ref	999 (999 to 999)	37.3 (21.6 to 64.6)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	21.5 (10.5 to 44.2)
6-months post IMP dose 2 - Ref	999 (999 to 999)	18.6 (9.1 to 38.0)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	99999 (99999 to 99999)
12-months post IMP dose 2 - Ref	999 (999 to 999)	21.0 (5.3 to 83.5)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	99999 (99999 to 99999)
6-months post IMP dose 2+preIMP dose 3 - Ref	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	10.0 (3.3 to 30.2)
1-week post IMP dose 3 - Ref	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	82.0 (52.7 to 127.6)
1-month post IMP dose 3 - Ref	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	74.2 (34.7 to 158.7)
12-mths post dose 2+6-mths post dose 3 - Ref	999 (999 to 999)	9999 (9999 to 9999)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)	32.0 (10.8 to 95.2)

No statistical analyses for this end point

Secondary: Part A - Percentage of participants achieving SR in Terms of NT at Each Post Vaccination Time Point

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End point title

Part A - Percentage of participants achieving SR in Terms of NT at Each Post Vaccination Time Point ^[47]

End point description

For BNT162b2-experienced participants (defined as participants who have previously received two injections of 30 μg BNT162b2). Reference and VOC specific NT. SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For participants with a baseline titer less than the LLOQ, SR is defined as a post-vaccination titer of ≥4 × LLOQ. Pre IMP dose 2 is also 2 months post dose 1 for Cohort 2 and 3 weeks post dose 1 for Cohort 6. Immunogenicity Analysis Set. 999 = not applicable since Cohorts 1, 3, 4 and 5 received only 1 dose of IMP. 9999 = not applicable since Cohort 2 received dose 2 on Day 56 and did not receive dose 3. 99999 = not applicable since Cohort 6 received dose 2 on Day 21 and received dose 3 approximately 6 months after dose 2.

End point type

Secondary

End point timeframe

Day 1 to Day 421

Notes
[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: This endpoint only reports data for Part A (Cohorts 1-6).

End point values	Part A - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)
Number of subjects analysed	21	20	20	20	20	17
Units: Percentage of participants
number (not applicable)
1-week post IMP dose 1 - B.1.1.7	93.3	100	100	66.7	94.1	33.3
3-weeks post IMP dose 1 - B.1.1.7	94.4	94.7	94.7	65.0	100	99999
1-month post IMP dose 1 - B.1.1.7	94.1	95.0	100	65.0	88.2	99999
6-months post IMP dose 1 - B.1.1.7	64.3	9999	83.3	47.4	75.0	99999
12-months post IMP dose 1 - B.1.1.7	80.0	9999	64.3	54.5	90.9	99999
Pre IMP dose 2 - B.1.1.7	999	61.1	999	999	999	43.8
1-week post IMP dose 2 - B.1.1.7	999	100	999	999	999	100
1-month post IMP dose 2 - B.1.1.7	999	94.4	999	999	999	92.9
6-months post IMP dose 2+pre IMP dose 3 - B.1.1.7	999	9999	999	999	999	63.6
1-week post IMP dose 3 - B.1.1.7	999	9999	999	999	999	100
1-month post IMP dose 3 - B.1.1.7	999	9999	999	999	999	100
6-months post IMP dose 2 - B.1.1.7	999	87.5	999	999	999	99999
12-mths post dose 2+6-mths post dose 3 – B.1.1.7	999	9999	999	999	999	100
12-months post IMP dose 2 - B.1.1.7	999	88.9	999	999	999	99999
1-week post IMP dose 1 - B.1.617.2	93.8	100	100	100	88.2	33.3
3-weeks post IMP dose 1 - B.1.617.2	94.4	94.7	100	100	93.8	99999
1-month post IMP dose 1 - B.1.617.2	100	95.0	94.7	100	88.2	99999
6-months post IMP dose 1 - B.1.617.2	78.6	9999	88.9	73.7	58.3	99999
12-months post IMP dose 1 - B.1.617.2	90.0	9999	57.1	81.1	81.8	99999
Pre IMP dose 2 - B.1.617.2	999	94.4	999	999	999	29.9
1-week post IMP dose 2 - B.1.617.2	999	100	999	999	999	100
1-month post IMP dose 2 - B.1.617.2	999	94.4	999	999	999	92.9
6-months post IMP dose 2+preIMP dose 3 - B.1.617.2	999	9999	999	999	999	72.7
1-week post IMP dose 3 - B.1.617.2	999	9999	999	999	999	100
1-month post IMP dose 3 - B.1.617.2	999	9999	999	999	999	100
6-months post IMP dose 2 - B.1.617.2	999	81.3	999	999	999	99999
12-mths post dose 2+6-mths post dose 3 – B.1.617.2	999	9999	999	999	999	100
12-months post IMP dose 2 - B.1.617.2	999	88.9	999	999	999	99999
1-week post IMP dose 1 - Ref	100	100	100	86.7	94.1	33.3
3-weeks post IMP dose 1 - Ref	100	100	94.7	95.0	100	99999
1-month post IMP dose 1 - Ref	100	95	94.7	95.0	100	99999
6-months post IMP dose 1 - Ref	64.3	9999	83.3	36.8	58.3	99999
12-months post IMP dose 1 - Ref	90.0	9999	85.7	54.5	90.9	99999
Pre IMP dose 2 - Ref	999	94.4	999	999	999	43.8
1-week post IMP dose 2 - Ref	999	100	999	999	999	100
1-month post IMP dose 2 - Ref	999	100	999	999	999	85.7
6-months post IMP dose 2+pre IMP dose 3 - Ref	999	9999	999	999	999	54.5
1-week post IMP dose 3 - Ref	999	9999	999	999	999	100
1-month post IMP dose 3 - Ref	999	9999	999	999	999	100
6-months post IMP dose 2 - Ref	999	93.8	999	999	999	99999
12-mths post dose 2+6-mths post dose 3 – Ref	999	9999	999	999	999	100
12-months post IMP dose 2 - Ref	999	88.9	999	999	999	99999

No statistical analyses for this end point

Secondary: Part B - GMT of VOCs and reference strains in Part B C1 and Control

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End point title

Part B - GMT of VOCs and reference strains in Part B C1 and Control ^[48]

End point description

GMTs of VOCs (B.1.1.7 and B.1.617.2) and reference strain 1 month after 1 dose of BNT162 (B.1.1.7+B.1.167.2) in participants from Part B Cohort 1 of the BNT162-17 trial (BNT162b2-experienced participants), and reference strain 1 month after 2 doses of BNT162b2 in selected participants from the Phase III C4591001 trial. GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ. Immunogenicity Analysis Set.

End point type

Secondary

End point timeframe

1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 trial

Notes
[48] - 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: This endpoint only reports data for Part B - Cohort 1 and C4591001 BNT162b2 30 μg (control group).

End point values	Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	C4591001 BNT162b2 30 μg
Number of subjects analysed	299	332
Units: Titer
geometric mean (confidence interval 95%)
B.1.1.7	996.5 (880.3 to 1128.0)	74.7 (66.1 to 84.3)
B.1.617.2	552.4 (495.2 to 616.2)	65.2 (57.5 to 74.0)
Reference strain	947.0 (846.4 to 1059.5)	113.3 (101.4 to 126.5)

No statistical analyses for this end point

Secondary: Part B - GMT of VOCs and reference strains in Part B C4 and Control

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End point title

Part B - GMT of VOCs and reference strains in Part B C4 and Control ^[49]

End point description

GMTs of VOCs (B.1.617.2) and reference strain 1 month after 1 dose of BNT162 (B.1.167.2) in participants from Part B Cohort 4 of the BNT162-17 trial (BNT162b2-experienced participants), and 1 month after 2 doses of BNT162b2 in selected participants from the Phase III C4591001 trial. GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ. Immunogenicity Analysis Set.

End point type

Secondary

End point timeframe

1 month after booster dose in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 trial

Notes
[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: This endpoint only reports data for Part B - Cohort 4 and C4591001 BNT162b2 30 μg (control group).

End point values	Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	C4591001 BNT162b2 30 μg
Number of subjects analysed	317	320
Units: Titer
geometric mean (confidence interval 95%)
B.1.1.7	972.8 (875.3 to 1081.3)	78.6 (69.6 to 88.8)
B.1.617.2	730.5 (654.5 to 815.3)	71.2 (62.7 to 80.8)
Reference strain	1005.3 (900.3 to 1122.5)	113.0 (100.5 to 127.1)

No statistical analyses for this end point

Secondary: Part B - GMT of VOCs and Reference Strain in Part B C6 1 Month After Dose 2 and 1 Month After Dose 3

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End point title

Part B - GMT of VOCs and Reference Strain in Part B C6 1 Month After Dose 2 and 1 Month After Dose 3 ^[50]

End point description

GMTs of VOCs and reference strain NT 1 month after dose 2 and dose 3 of BNT162b2 (B.1.1.7 + B.1.617.2) (Part B - Cohort 6). GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ. Immunogenicity Analysis Set.

End point type

Secondary

End point timeframe

1 month after Dose 2 and 1 month after Dose 3

Notes
[50] - 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: This endpoint only reports data for Part B - Cohort 6.

End point values	Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)
Number of subjects analysed	359
Units: Titer
geometric mean (confidence interval 95%)
1 month post IMP dose 2 - B.1.1.7	832.5 (718.2 to 965.0)
1 month post IMP dose 3 - B.1.1.7	942.6 (836.4 to 1062.4)
1 month post IMP dose 2 - B.1.617.2	1184.6 (1015.5 to 1381.9)
1 month post IMP dose 3 - B.1.617.2	1270.9 (1130.2 to 1429.0)
1 month post IMP dose 2 - Reference strain	697.5 (594.0 to 819.1)
1 month post IMP dose 3 - Reference strain	830.5 (736.3 to 936.8)

No statistical analyses for this end point

Secondary: Part B - GMTs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection in Part B C6 (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection in Part B C1 (1 Booster Dose)

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End point title

Part B - GMTs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection in Part B C6 (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection in Part B C1 (1 Booster Dose)

End point description

GMTs of VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 [Omicron BA.5]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6), 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants without evidence of infection (Cohort 6), and 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ; assay results above the ULOQ were set to ULOQ. Immunogenicity Analysis Set.

End point type

Secondary

End point timeframe

Day 1 up to 1 month after 1 booster dose in Part B Cohort 1 without evidence of infection, up to 1 month after 2 doses in Part B Cohort 6 without evidence of infection and up to 3 weeks after 1 dose in Part B Cohort 6 with evidence of prior infection

End point values	Part B - C6: BNT162b2 With Evidence of Prior Infection	Part B - C6: BNT162b2 Without Evidence of Infection	Part B - C1: BNT162b2 Without Evidence of Infection
Number of subjects analysed	142	17	136
Units: Titer
geometric mean (confidence interval 95%)
SARS-CoV-2 neutralization assay – B.1.1.7	1045.3 (853.1 to 1280.8)	180.8 (91.8 to 356.3)	749.5 (621.1 to 904.6)
SARS-CoV-2 neutralization assay – B.1.617.2	859.9 (693.4 to 1066.4)	62.6 (30.9 to 127.0)	466.6 (401.8 to 541.9)
SARS-CoV-2 neutralization assay – B.1.1.529.5	229.3 (191.7 to 274.4)	10.2 (5.7 to 18.3)	80.8 (66.9 to 97.6)

No statistical analyses for this end point

Secondary: Part B - GMRs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

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End point title

Part B - GMRs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

End point description

GMR of VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 [Omicron BA.5]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6) to the VOCs NTs 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in participants without evidence of infection (Cohort 6), and to the VOCs NTs 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). GMRs and 2-sided 95% CIs were calculated by exponentiating the difference of the LS means and corresponding CIs based on the analysis of logarithmically transformed neutralizing titers using a linear regression model with terms of age, sex, and group. A separate model was fit for each comparison. Assay results below the LLOQ were set to 0.5 × LLOQ; assay results above the ULOQ were set to ULOQ. Immunogenicity Analysis Set.

End point type

Secondary

End point timeframe

Day 1 to Day 29

End point values	Part B - C6 With Prior Infection / C6 Without Prior Infection	Part B - C6 With Prior Infection / C1 Without Prior Infection
Number of subjects analysed	159	278
Units: Titer ratio
geometric mean (confidence interval 95%)
SARS-CoV-2 neutralization assay – B.1.1.7	7.66 (4.09 to 14.33)	1.46 (1.10 to 1.93)
SARS-CoV-2 neutralization assay – B.1.617.2	15.43 (7.87 to 30.28)	1.88 (1.44 to 2.45)
SARS-CoV-2 neutralization assay – B.1.1.529.5	29.86 (17.31 to 51.49)	2.94 (2.26 to 3.82)

No statistical analyses for this end point

Secondary: Part B - Difference in SRs to VOCs in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

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End point title

Part B - Difference in SRs to VOCs in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

End point description

The difference in SRs to VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 [Omicron BA.5]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6) to those 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in participants without evidence of infection (Cohort 6), and to those 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). Adjusted difference in proportions estimated using minimum risk weights and stratified by sex and age group (18 to 55 years, 56 to 85 years), expressed as a percentage. 2-Sided CI based on the Newcombe method stratified by sex and age group (18 to 55 years, 56 to 85 years) with minimum risk weights for the difference in proportions. Immunogenicity Analysis Set.

End point type

Secondary

End point timeframe

Day 1 to Day 29

End point values	Part B - C6 With Prior Infection / C6 Without Prior Infection	Part B - C6 With Prior Infection / C1 Without Prior Infection
Number of subjects analysed	159	278
Units: Percentage difference
number (confidence interval 95%)
SARS-CoV-2 neutralization assay – B.1.1.7	6.95 (-9.69 to 32.17)	-9.75 (-16.43 to -3.24)
SARS-CoV-2 neutralization assay – B.1.617.2	20.90 (-0.62 to 46.52)	-6.56 (-13.03 to -0.37)
SARS-CoV-2 neutralization assay – B.1.1.529.5	81.47 (54.28 to 90.07)	6.67 (-2.06 to 15.42)

No statistical analyses for this end point

Secondary: Part B - SR of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

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End point title

Part B - SR of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

End point description

SRs of VOC specific NTs (B.1.1.7, B.1.617.2, B.1.1.529.5 [Omicron BA.5]) 3 weeks after one dose of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 vaccine-naïve participants with evidence of prior infection (Cohort 6) 1 month after two doses of BNT162b2 (B.1.1.7 + B.1.617.2) in participants without evidence of infection (Cohort 6), and 1 month after one booster dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants without evidence of infection (Cohort 1). Seroresponse was defined as achieving a ≥4-fold rise from baseline. If the baseline measurement was below the LLOQ, a postvaccination assay result ≥4 × LLOQ was considered a seroresponse. Immunogenicity Analysis Set.

End point type

Secondary

End point timeframe

3 weeks after one dose in participants with evidence of prior infection (Cohort 6), 1 month after two doses in participants without evidence of infection (Cohort 6), and 1 month after one booster dose (Cohort 1)

End point values	Part B - C6: BNT162b2 With Evidence of Prior Infection	Part B - C6: BNT162b2 Without Evidence of Infection	Part B - C1: BNT162b2 Without Evidence of Infection
Number of subjects analysed	142	17	136
Units: Percentage of participants
number (confidence interval 95%)
SARS-CoV-2 neutralization assay – B.1.1.7	87.3 (80.7 to 92.3)	76.5 (50.1 to 93.2)	97.1 (92.6 to 99.2)
SARS-CoV-2 neutralization assay – B.1.617.2	89.4 (83.2 to 94.0)	58.8 (32.9 to 81.6)	96.3 (91.6 to 98.8)
SARS-CoV-2 neutralization assay – B.1.1.529.5	87.3 (80.7 to 92.3)	11.8 (1.5 to 36.4)	80.1 (72.4 to 86.5)

No statistical analyses for this end point

Secondary: Part C - GMT - B.1.1.529.1 in RNA Based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection

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End point title

Part C - GMT - B.1.1.529.1 in RNA Based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection ^[51]

End point description

VOC NT in RNA-based COVID-19 vaccine-experienced participants with history of SARS-CoV-2 infection at baseline and 7 days, 1 month, and 3 months after the trial start for Cohorts 7, 8, and 9, and 6 and 12 months after the trial start for Cohorts 7 and 8. GMTs and 2-sided 95% CIs are calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ are set to 0.5 × LLOQ and above the ULOQ are set to ULOQ. Number of subjects with valid and determinate assay results for the specified variant at the given dose/sampling time point. No vaccination was given to Cohort 9 participants within 3 months after Visit 1. The term "post IMP" does not apply for Cohort 9 since no IMP was given, but blood was collected at the same timepoints post randomization. Immunogenicity Analysis Set.

End point type

Secondary

End point timeframe

Day 1 to Day 360

Notes
[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: This endpoint only reports data for Part C (Cohorts 7, 8 and 9).

End point values	Part C - C7: 1 Dose of 30 μg BNT162b2 (B.1.1.529.1)	Part C - C8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part C - C9: No Vaccination
Number of subjects analysed	68	59	28
Units: Titer
geometric mean (confidence interval 95%)
Baseline	169.2 (124.4 to 230.2)	388.5 (262.0 to 575.9)	164.0 (96.1 to 280.0)
1-week post IMP Dose 1	751.7 (571.5 to 988.9)	768.9 (550.0 to 1074.9)	211.7 (122.5 to 365.9)
1-month post IMP Dose 1	748.8 (572.0 to 980.3)	801.5 (569.8 to 1127.4)	180.4 (106.7 to 305.0)
3-months post IMP Dose 1	590.3 (433.6 to 803.6)	571.5 (411.5 to 793.8)	143.3 (86.7 to 236.9)
6-months post IMP Dose 1	289.6 (210.7 to 397.9)	356.8 (266.9 to 476.8)	999 (999 to 999)
12-months post IMP Dose 1	197.0 (142.5 to 272.3)	180.5 (135.9 to 239.8)	999 (999 to 999)

No statistical analyses for this end point

Secondary: Part B - SR of of VOCs and Reference Strains in Part B C1 and Control

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End point title

Part B - SR of of VOCs and Reference Strains in Part B C1 and Control ^[52]

End point description

Percentage of participants achieving SR at 1 month after 1 dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced participants (Cohort 1) and 1 month after 2 doses of BNT162b2 primary series (participants from C4591001). SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For participants with a baseline titer less than the LLOQ, SR is defined as a post-vaccination titer of ≥4 × LLOQ. Immunogenicity Analysis Set.

End point type

Secondary

End point timeframe

1 month after Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (2020-002641-42) trial

Notes
[52] - 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: This endpoint only reports data for Part B - Cohort 1 and C4591001 BNT162b2 30 μg (control group).

End point values	Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	C4591001 BNT162b2 30 μg
Number of subjects analysed	298	332
Units: Percentage of participants
number (confidence interval 95%)
B.1.1.7	88.6 (84.4 to 92.0)	76.2 (71.3 to 80.7)
B.1.617.2	85.9 (81.4 to 89.6)	74.4 (69.3 to 79.0)
Reference strain	89.6 (85.6 to 92.8)	88.3 (84.3 to 91.5)

No statistical analyses for this end point

Secondary: Part B - SR of of VOCs and Reference Strains in Part B C4 and Control

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End point title

Part B - SR of of VOCs and Reference Strains in Part B C4 and Control ^[53]

End point description

Percentage of participants achieving SR at 1 month after 1 dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced subjects (Part B - Cohort 4) and 1 month after 2 doses of BNT162b2 primary series (participants from C4591001). SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For participants with a baseline titer less than the LLOQ, SR is defined as a post-vaccination titer of ≥4 × LLOQ. Immunogenicity Analysis Set.

End point type

Secondary

End point timeframe

1 month after Dose 1 in BNT162-17 participants and 1 month post Dose 2 in participants from the C4591001 (2020-002641-42) trial

Notes
[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: This endpoint only reports data for Part B - Cohort 4 and C4591001 BNT162b2 30 μg (control group).

End point values	Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	C4591001 BNT162b2 30 μg
Number of subjects analysed	313	320
Units: Percentage of participants
number (confidence interval 95%)
B.1.1.7	96.5 (93.8 to 98.2)	78.4 (73.5 to 82.8)
B.1.617.2	97.4 (95.0 to 98.9)	77.5 (72.5 to 82.0)
Reference strain	98.1 (95.9 to 99.3)	87.5 (83.4 to 90.9)

No statistical analyses for this end point

Secondary: Part B - C6 - Percentages with SRs to VOCs (B.1.1.7, B.1.617.2) and reference strain

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End point title

Part B - C6 - Percentages with SRs to VOCs (B.1.1.7, B.1.617.2) and reference strain ^[54]

End point description

Percentage of participants achieving SR to VOCs (B.1.1.7, B.1.617.2) and reference strain at 1 month after dose 2 and dose 3 of BNT162b2 (B.1.1.7 + B.1.617.2) (Part B - Cohort 6). SR is defined as a ≥4-fold rise in neutralizing titer from baseline (pre IMP dose 1). For participants with a baseline titer less than the LLOQ, SR is defined as a post vaccination titer of ≥4 × LLOQ. Pre IMP dose 2 is also 3 weeks post dose 1 for Cohort 6. Immunogenicity Analysis Set.

End point type

Secondary

End point timeframe

1 month after Dose 2 and 1 month after Dose 3

Notes
[54] - 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: This endpoint only reports data for Part B - Cohort 6.

End point values	Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)
Number of subjects analysed	359
Units: Percentage of participants
number (confidence interval 95%)
1 month post IMP dose 2 - B.1.1.7	86.8 (82.2 to 90.5)
1 month post IMP dose 3 - B.1.1.7	83.6 (78.8 to 87.7)
1 month post IMP dose 2 - B.1.617.2	88.9 (84.7 to 92.4)
1 month post IMP dose 3 - B.1.617.2	87.1 (82.7 to 90.8)
1 month post IMP dose 2 - Reference strain	87.5 (83.0 to 91.1)
1 month post IMP dose 3 - Reference strain	89.5 (85.4 to 92.8)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AEs: From Dose 1 to 1 Month after each dose; SAEs: From Dose 1 up to end of study, i.e., up to 18 months.

Adverse event reporting additional description

35 participants were randomized to Part C - Cohort 9 but, as per protocol, these participants did not receive treatment and therefore adverse event data were not collected for these participants.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.1

Reporting group title

Part A - C1: 1 Dose of 30 μg BNT162b2 (B.1.1.7 + B.1.617)

Reporting group description

Participants in Part A - Cohort 1 received 1 dose of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection on Day 1

Reporting group title

Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Reporting group description

Participants in Part A - Cohort 2 received 2 doses of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection one on Day 1 and one on Day 56

Reporting group title

Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)

Reporting group description

Participants in Part A - Cohort 3 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.1.7) on Day 1

Reporting group title

Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)

Reporting group description

Participants in Part A - Cohort 4 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.617.2) on Day 1

Reporting group title

Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)

Reporting group description

Participants in Part A - Cohort 5 received 1 dose of 30 μg BNT162b2 original vaccine on Day 1. 21 subjects assigned to Part B Cohort 4 actually received BNT162b2 (treatment of Part A Cohort 5) and therefore were included in the analyses of safety set of Part A Cohort 5 and excluded from Part B safety set

Reporting group title

Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Reporting group description

Reporting group title

Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Reporting group description

Participants in Part B - Cohort 1 received 1 dose of 30 μg multivalent vaccine BNT162b2 (B.1.1.7 + B.1.617.2) as a single injection on Day 1

Reporting group title

Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)

Reporting group description

Participants in Part B - Cohort 4 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.617.2) on Day 1

Reporting group title

Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)

Reporting group description

Reporting group title

Part C - C7: 1 Dose of 30 μg BNT162b2 (B.1.1.529.1)

Reporting group description

Participants in Part C - Cohort 7 received 1 dose of 30 μg monovalent vaccine BNT162b2 (B.1.1.529.1) on Day 1

Reporting group title

Part C - C8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)

Reporting group description

Participants in Part C - Cohort 8 received 1 dose of 30 μg BNT162b2 original vaccine on Day 1

Serious adverse events	Part A - C1: 1 Dose of 30 μg BNT162b2 (B.1.1.7 + B.1.617)	Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - C7: 1 Dose of 30 μg BNT162b2 (B.1.1.529.1)	Part C - C8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 21 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	6 / 349 (1.72%)	9 / 352 (2.56%)	13 / 361 (3.60%)	0 / 72 (0.00%)	5 / 71 (7.04%)
number of deaths (all causes)	0	0	0	0	0	0	1	0	2	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	1	0	2	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lipoma
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	1 / 352 (0.28%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Papillary thyroid cancer
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal cancer
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	1 / 352 (0.28%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	1 / 361 (0.28%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	1 / 349 (0.29%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	1 / 352 (0.28%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Social circumstances
Physical assault
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	1 / 349 (0.29%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	2 / 352 (0.57%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	1 / 352 (0.28%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	1 / 361 (0.28%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	1 / 349 (0.29%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fibula fracture
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower limb fracture
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Stab wound
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	1 / 361 (0.28%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	1 / 352 (0.28%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Arrhythmia
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	1 / 349 (0.29%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cor pulmonale
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	1 / 361 (0.28%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	1 / 349 (0.29%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myocarditis
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	1 / 352 (0.28%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	1 / 361 (0.28%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Inguinal hernia
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	1 / 352 (0.28%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obstructive pancreatitis
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	1 / 361 (0.28%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatitis acute
subjects affected / exposed	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	1 / 349 (0.29%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	1 / 361 (0.28%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Mobility decreased
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	1 / 352 (0.28%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rhabdomyolysis
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	1 / 349 (0.29%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	1 / 352 (0.28%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	1 / 361 (0.28%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	1 / 349 (0.29%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epiglottitis
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	1 / 361 (0.28%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Localized infection
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	1 / 361 (0.28%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	1 / 349 (0.29%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	1 / 361 (0.28%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	1 / 361 (0.28%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	1 / 349 (0.29%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	1 / 349 (0.29%)	0 / 352 (0.00%)	1 / 361 (0.28%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	1 / 361 (0.28%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part A - C1: 1 Dose of 30 μg BNT162b2 (B.1.1.7 + B.1.617)	Part A - C2: 2 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part A - C3: 1 Dose of 30 μg BNT162b2 (B.1.1.7)	Part A - C4: 1 Dose of 30 μg BNT162b2 (B.1.617.2)	Part A - C5: 1 Dose of 30 μg BNT162b2 (Original Vaccine)	Part A - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C1: 1 Dose 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part B - C4: 1 Dose 30 μg BNT162b2 (B.1.617.2)	Part B - C6: 3 Doses of 30 μg BNT162b2 (B.1.1.7 + B.1.617.2)	Part C - C7: 1 Dose of 30 μg BNT162b2 (B.1.1.529.1)	Part C - C8: 1 Dose of 30 μg BNT162b2 (Original Vaccine)
Total subjects affected by non serious adverse events
subjects affected / exposed	2 / 21 (9.52%)	7 / 20 (35.00%)	4 / 20 (20.00%)	0 / 20 (0.00%)	27 / 42 (64.29%)	6 / 17 (35.29%)	26 / 349 (7.45%)	0 / 352 (0.00%)	39 / 361 (10.80%)	4 / 72 (5.56%)	5 / 71 (7.04%)
Injury, poisoning and procedural complications
Product administration error
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	22 / 42 (52.38%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences all number	0	0	0	0	22	0	0	0	0	0	0
Nervous system disorders
Ageusia
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 17 (5.88%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Anosmia
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 17 (5.88%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Headache
subjects affected / exposed	1 / 21 (4.76%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	3 / 17 (17.65%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	4 / 71 (5.63%)
occurrences all number	1	1	1	1	1	4	0	0	0	0	4
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	1 / 21 (4.76%)	1 / 20 (5.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	0 / 17 (0.00%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	4 / 72 (5.56%)	1 / 71 (1.41%)
occurrences all number	1	1	2	0	1	0	0	0	0	4	1
General disorders and administration site conditions
Fatigue
subjects affected / exposed	1 / 21 (4.76%)	4 / 20 (20.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	2 / 42 (4.76%)	2 / 17 (11.76%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences all number	1	7	2	0	2	2	0	0	0	0	0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 21 (0.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 42 (2.38%)	1 / 17 (5.88%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences all number	0	3	0	0	1	1	0	0	0	0	0
Nausea
subjects affected / exposed	0 / 21 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 17 (5.88%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences all number	0	1	1	0	0	1	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	2 / 17 (11.76%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0
Nasal congestion
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	2 / 17 (11.76%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 17 (5.88%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 17 (5.88%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 17 (5.88%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Infections and infestations
COVID-19
subjects affected / exposed	0 / 21 (0.00%)	2 / 20 (10.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 17 (5.88%)	26 / 349 (7.45%)	0 / 352 (0.00%)	39 / 361 (10.80%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences all number	0	2	1	0	0	1	26	0	42	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 42 (0.00%)	1 / 17 (5.88%)	0 / 349 (0.00%)	0 / 352 (0.00%)	0 / 361 (0.00%)	0 / 72 (0.00%)	0 / 71 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

27 Aug 2021

The amendment implemented updates in response to Center for Biologics Evaluation and Research (CBER) comments (dated 07 AUG 2021) on protocol version 1.0.

05 Nov 2021

The amendment implemented updates for clarification, updates reflecting the decision to perform SAR-CoV-2 viral genome sequencing for all participants (and not just if triggered), and adaptions to the statistical analysis reflecting discussion of booster data analysis with the FDA which requires the exclusion of certain protocol deviations from the primary analysis and thereby makes the Per Protocol Set redundant.

24 Feb 2022

This amendment implemented three additional cohorts (Cohorts 7, 8, and 9) within Part C, comprising an additional ~410 participants who: • have received two or three doses of any authorized COVID-19 RNA-based vaccine, e.g., 30 μg BNT162b2 (Comirnaty) or the Moderna vaccine (Spikevax), and • had a breakthrough SARS-CoV-2 infection from January 2022 on (limited to a period when there was a high prevalence of SARS-CoV-2 Omicron infections). Participants in Part C will receive either 30 μg of the monovalent BNT162b2 (B.1.1.529) as a third or fourth dose, 30 μg BNT162b2 as a third or fourth dose, or no vaccination within 3 months of Visit 1. In addition, a third dose of the multivariant vaccine has been added for Cohort 6, Parts A and B comprising BNT162b2-naïve participants, with planned visits at pre-Dose 3, 1-week post-Dose 3, and 1-month post-Dose 3. For participants who receive non-trial SARS-CoV-2 vaccinations, blood samples for humoral immunogenicity and T-cell and B-cell response assessments will not be collected, and they will be discontinued from the BNT162-17 trial. The amendment also includes updates for clarification and an updated Table 8, which following the request of the IEC in Germany now includes information on the SARS-CoV-2 Omicron variant.

01 Aug 2022

This update implemented a change in eligibility criteria for Part C. Eligibility criteria were updated to correspond to the existing regulatory guidance, clarifying the required time frame between the last dose of the COVID-19 RNA-based vaccine and first IMP dose. The two-month window between the documented SARS-CoV-2 infection and trial IMP administration was implemented to reduce heterogeneity in baseline VNT levels which may affect immune responses after trial vaccine administration. The mandatory NAAT test as a confirmation of prior SARS-CoV-2 infection was adjusted according to suggested updated algorithms for SARS-CoV-2 infection diagnostics. In addition, based on the recent immunogenicity data from the BNT162b2 Omicron variant vaccine in the BNT162-16 trial, the sample size and expected GMR were adjusted accordingly.

04 Aug 2022

This update implemented a correction, specifically the insertion of Table 5.

28 Jun 2023

This amendment implemented updates in response to FDA comments (dated 08 JUN 2023) and the decision to include additional immunogenicity analyses in the primary objectives and secondary objectives for COVID-19 vaccine-naïve participants (Cohort 6) in Part B. * Several sections were Updated to reflect the additional immunogenicity analyses * Updates to clarify that the original Omicron strain B.1.1.529 has since been renamed B.1.1.529.1 (known as Omicron BA.1), with the Omicron lineage having expanded into multiple sublineages. * The sponsors medical representative was updated. The document history was updated to reflect this update. * Trial rationale was updated to reflect the current BNt162b2 authorization status. Updates to clarify that the original Omicron strain B.1.1.529 has since been renamed B.1.1.529.1 (known as Omicron BA.1), with the Omicron lineage having expanded into multiple sublineages. Updates to explain how the data from Part B of the trial will be used. * Objectives and endpoints were updated to add clarification, to reflect the additional immunogenicity analyses, and corrections. This included the addition of two Primary objectives (Immunogenicity) and two secondary objectives for Part B. * Sections "Trial design" and "Overall design": Updated to reflect addition of new analyses. * Schedule of activities section updated to reflect change from “BNT162-naïve participants” to “COVID-19 vaccine-naïve participants” * Updates to reflect the current disease status. * Risk assessment was updated to add data cutoff dates. * Section "Measures to minimize bias randomization and blinding": Text updated for clarification. * Section "Regulatory reporting requirements for SAEs": Text updated for clarify where to find reference safety information in the current BNT162 IB. * Section "Reporting of SAEs and AESIs": Updates for clarifications on the new e-mail addresses and fax number for safety reporting.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase II trial to evaluate the safety and immunogenicity of SARS-CoV-2 monovalent and multivalent RNA-based vaccines in healthy subjects

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: All Parts - Percentage of Participants Reporting Local Reactions at the Injection Site (Pain, Tenderness, Erythema/ Redness, Induration/Swelling)

Primary: All Parts - Percentage of Participants Reporting Local Reactions at the Injection Site (Pain, Tenderness, Erythema/ Redness, Induration/Swelling)

Primary: All Parts - Percentage of Participants Reporting Systemic Events (Fever, Fatigue, Headache, Chills, Vomiting, Nausea, Diarrhea, New or Worsened Muscle Pain, and New or Worsened Joint Pain)

Primary: All Parts - Percentage of Participants Reporting Systemic Events (Fever, Fatigue, Headache, Chills, Vomiting, Nausea, Diarrhea, New or Worsened Muscle Pain, and New or Worsened Joint Pain)

Primary: All Parts - Percentage of Participants Reporting Adverse Events (AEs)

Primary: All Parts - Percentage of Participants Reporting Adverse Events (AEs)

Primary: All Parts - Percentage of Participants Reporting Serious Adverse Events (SAEs)

Primary: All Parts - Percentage of Participants Reporting Serious Adverse Events (SAEs)

Primary: Part B - GMR of B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (2020-002641-42) Trial

Primary: Part B - GMR of B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 (2020-002641-42) Trial

Primary: Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

Primary: Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

Primary: Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

Primary: Part B - GMR of B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

Primary: Part B - Difference in Seroresponse (SR) to B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001

Primary: Part B - Difference in Seroresponse (SR) to B.1.1.7 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001

Primary: Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2- experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001

Primary: Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in BNT162b2- experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001

Primary: Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (2020-002641-42)

Primary: Part B - Difference in SR to B.1.617.2 NT 1 Month After 1 Dose of BNT162b2 (B.1.617.2) in BNT162b2-experienced Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From C4591001 (2020-002641-42)

Primary: Part B - GMR of B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

Primary: Part B - GMR of B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

Primary: Part B - GMR of B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

Primary: Part B - GMR of B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

Primary: Part B - The Difference in SR to B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

Primary: Part B - The Difference in SR to B.1.1.7 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

Primary: Part B - The Difference in SR to B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

Primary: Part B - The Difference in SR to B.1.617.2 NT 1 Month After 2 Doses of BNT162b2 (B.1.1.7 + B.1.617.2) in COVID-19 Vaccine-naïve Participants to the Reference Strain NT 1 Month After 2 Doses of BNT162b2 in Participants From the Phase III C4591001 Trial

Primary: Part B - GMR of Reference Strain NT After One Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in Participants With Evidence of Prior Infection to the Reference Strain NT After 2 Doses of BNT162b2 in Participants Without Evidence of Infection

Primary: Part B - GMR of Reference Strain NT After One Dose of BNT162b2 (B.1.1.7 + B.1.617.2) in Participants With Evidence of Prior Infection to the Reference Strain NT After 2 Doses of BNT162b2 in Participants Without Evidence of Infection

Primary: Part B - The Difference in SRs to the Reference Strain NT in Participants With Evidence of Prior Infection and to the Reference Strain NT in Participants Without Evidence of Infection (COVID-19 Vaccine-naïve Participants)

Primary: Part B - The Difference in SRs to the Reference Strain NT in Participants With Evidence of Prior Infection and to the Reference Strain NT in Participants Without Evidence of Infection (COVID-19 Vaccine-naïve Participants)

Primary: Part C - GMR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 and 8

Primary: Part C - GMR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 and 8

Primary: Part C - The Difference in SR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 & 8

Primary: Part C - The Difference in SR of B.1.1.529.1 NT 1 Month After One Dose of BNT162b2 (B.1.1.529.1) in RNA-based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection to Those at 1 Month After One Dose of BNT162b2 for Cohorts 7 & 8

Secondary: Part A - Geometric Mean Titer (GMT) at Each Timepoint

Secondary: Part A - Geometric Mean Titer (GMT) at Each Timepoint

Secondary: Part A - Geometric Mean Fold Rises (GMFR) From Before Vaccination to Each Subsequent Time Point After Vaccination

Secondary: Part A - Geometric Mean Fold Rises (GMFR) From Before Vaccination to Each Subsequent Time Point After Vaccination

Secondary: Part A - Percentage of participants achieving SR in Terms of NT at Each Post Vaccination Time Point

Secondary: Part A - Percentage of participants achieving SR in Terms of NT at Each Post Vaccination Time Point

Secondary: Part B - GMT of VOCs and reference strains in Part B C1 and Control

Secondary: Part B - GMT of VOCs and reference strains in Part B C1 and Control

Secondary: Part B - GMT of VOCs and reference strains in Part B C4 and Control

Secondary: Part B - GMT of VOCs and reference strains in Part B C4 and Control

Secondary: Part B - GMT of VOCs and Reference Strain in Part B C6 1 Month After Dose 2 and 1 Month After Dose 3

Secondary: Part B - GMT of VOCs and Reference Strain in Part B C6 1 Month After Dose 2 and 1 Month After Dose 3

Secondary: Part B - GMTs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection in Part B C6 (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection in Part B C1 (1 Booster Dose)

Secondary: Part B - GMTs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection in Part B C6 (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection in Part B C1 (1 Booster Dose)

Secondary: Part B - GMRs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

Secondary: Part B - GMRs of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

Secondary: Part B - Difference in SRs to VOCs in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

Secondary: Part B - Difference in SRs to VOCs in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

Secondary: Part B - SR of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

Secondary: Part B - SR of VOC in COVID-19 Vaccine-naïve Participants With and Without Evidence of Prior Infection (1 and 2 primary doses respectively) and in BNT162b2-Experienced Participants Without Evidence of Infection (1 Booster Dose)

Secondary: Part C - GMT - B.1.1.529.1 in RNA Based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection

Secondary: Part C - GMT - B.1.1.529.1 in RNA Based COVID-19 Vaccine-experienced Participants With History of SARS-CoV-2 Infection

Secondary: Part B - SR of of VOCs and Reference Strains in Part B C1 and Control

Secondary: Part B - SR of of VOCs and Reference Strains in Part B C1 and Control

Secondary: Part B - SR of of VOCs and Reference Strains in Part B C4 and Control

Secondary: Part B - SR of of VOCs and Reference Strains in Part B C4 and Control

Secondary: Part B - C6 - Percentages with SRs to VOCs (B.1.1.7, B.1.617.2) and reference strain

Secondary: Part B - C6 - Percentages with SRs to VOCs (B.1.1.7, B.1.617.2) and reference strain

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Clinical Trial Results:
A Phase II trial to evaluate the safety and immunogenicity of SARS-CoV-2 monovalent and multivalent RNA-based vaccines in healthy subjects