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Clinical Trial Results:
A Phase 3 Master Protocol to Evaluate Additional Dose(s) Of BNT162b2 In Healthy Individuals Previously Vaccinated With BNT162b2

Summary
EudraCT number	2021-005197-25
Trial protocol	DE
Global end of trial date	25 May 2023

Results information
Results version number	v2
This version publication date	12 Nov 2023
First version publication date	18 May 2023
Other versions	v1 , v3 , v4
Version creation reason

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

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Trial information

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Sponsor protocol code

C4591031

ISRCTN number

US NCT number

NCT04955626

WHO universal trial number (UTN)

Sponsor organisation name

BioNTech SE

Sponsor organisation address

An der Goldgrube 12, Mainz, Germany, 55131

Public contact

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

Scientific contact

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

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

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

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

Yes

Analysis stage

Interim

Date of interim/final analysis

01 Sep 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

25 May 2023

Was the trial ended prematurely?

Main objective of the trial

SSA: To describe efficacy of booster dose (BD) of BNT162b2 (BNT) against confirmed COVID-19 occurring from 7 days after BD through blinded follow-up period in subjects without evidence of past SARS-CoV-2 infection, with and without evidence of past SARS-CoV-2 infection. To define safety profile of BD of BNT. SSB: To describe frequency of elevated troponin I levels before and after BD of BNT or placebo. To define safety profile of a BD of BNT. SSF: To describe safety and tolerability profile of BNT (30 mcg/60 mcg), BNT OMI (30 mcg/60 mcg), combination of BNT and BNT OMI (30 mcg/60 mcg); to describe immune response to BNT (30 mcg/60 mcg), BNT OMI (30 mcg/60 mcg), combination of BNT and BNT OMI (30 mcg/60 mcg), given as fourth dose in BNT-experienced subjects.

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 trials subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

01 Jul 2021

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy

Long term follow-up duration

23 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Brazil: 1164

Country: Number of subjects enrolled

South Africa: 509

Country: Number of subjects enrolled

United States: 9882

Country: Number of subjects enrolled

Germany: 51

Country: Number of subjects enrolled

Israel: 122

Worldwide total number of subjects

11728

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)

551

Adults (18-64 years)

8739

From 65 to 84 years

2417

85 years and over

Subject disposition

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Recruitment details

Screening details

SSA: 10137 subjects enrolled, 10125 subjects vaccinated, 4 subjects were multiple enrolled. 10121 subjects evaluated. SSB: 1487 subjects randomised to receive study drug, 1485 subjects vaccinated and 1419 completed study. SSF: 123 subjects randomised to receive study drug. 122 subjects vaccinated and completed study.

Period 1 title

Overall Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer

Are arms mutually exclusive

Yes

SSA: BNT162b2 30 mcg: Blinded and Open Label Period

Arm description

Subjects received one dose (30 microgram) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Arm type

Experimental

Investigational medicinal product name

BNT162b2

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

30 microgram administered intramuscularly

SSA: Placebo: Blinded Period

Arm description

Subjects received placebo (normal saline solution of 0.9 percent [%] sodium chloride) intramuscularly.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Normal saline solution of 0.9 percent [%] sodium chloride

SSB: BNT162b2 30 mcg then Placebo

Arm description

Subjects received one dose (30 mcg) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm on Day 1 and received placebo (normal saline solution of 0.9 % sodium chloride) intramuscularly on Day 28.

Arm type

Experimental

Investigational medicinal product name

BNT162b2

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

30 microgram administered intramuscularly

SSB: Placebo then BNT162b2 30 mcg

Arm description

Subjects received placebo (normal saline solution of 0.9 % sodium chloride) intramuscularly on Day 1 and one dose (30 mcg) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm on Day 28.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Normal saline solution of 0.9 percent [%] sodium chloride

SSF: BNT162b2 30 mcg

Arm description

Subjects received one dose (30 mcg) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Arm type

Experimental

Investigational medicinal product name

BNT162b2

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

30 microgram administered intramuscularly

SSF: BNT162b2 60 mcg

Arm description

Subjects received one dose (60 mcg) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Arm type

Experimental

Investigational medicinal product name

BNT162b2

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

60 microgram administered intramuscularly

SSF: BNT162b2 OMI 30 mcg

Arm description

Subjects received one dose (30 mcg) of BNT162b2 Omicron (OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Arm type

Experimental

Investigational medicinal product name

BNT162b2

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

30 microgram administered intramuscularly

SSF: BNT162b2 OMI 60 mcg

Arm description

Subjects received one dose (60 mcg) of BNT162b2 Omicron (OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Arm type

Experimental

Investigational medicinal product name

BNT162b2

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

60 microgram administered intramuscularly

SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Arm description

Subjects received a total of 30 mcg BNT162b2 (15 mcg BNT162b2 and 15 mcg BNT162b2 OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Arm type

Experimental

Investigational medicinal product name

BNT162b2

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

30 microgram administered intramuscularly

SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Arm description

Subjects received a total of 60 mcg BNT162b2 (30 mcg BNT162b2 and 30 mcg BNT162b2 OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Arm type

Experimental

Investigational medicinal product name

BNT162b2

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

60 microgram administered intramuscularly

Number of subjects in period 1	SSA: BNT162b2 30 mcg: Blinded and Open Label Period	SSA: Placebo: Blinded Period	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Started	5080	5041	753	732	21	19	21	20	20	21
Completed	421	22	726	693	21	19	21	20	20	21
Not completed	4659	5019	27	39	0	0	0	0	0	0
Adverse event, serious fatal	-	2	-	-	-	-	-	-	-	-
Physician decision	1	1	-	3	-	-	-	-	-	-
Consent withdrawn by subject	26	62	14	16	-	-	-	-	-	-
No longer meets eligibility criteria	1	2	-	1	-	-	-	-	-	-
Adverse event, non-fatal	-	1	1	1	-	-	-	-	-	-
Subjects entered open label period	4544	4906	-	-	-	-	-	-	-	-
Unspecified	54	3	4	2	-	-	-	-	-	-
Lost to follow-up	28	28	7	14	-	-	-	-	-	-
Withdrawal by parent/guardian	-	-	1	1	-	-	-	-	-	-
Protocol deviation	5	14	-	1	-	-	-	-	-	-

Period 2 title

SSA: Blinded Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

SSA: BNT162b2 30 microgram: Blinded and Open Label Period

Arm description

Subjects received one dose (30 microgram) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Arm type

Experimental

Investigational medicinal product name

BNT162b2

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

30 microgram administered intramuscularly

SSA: Placebo: Blinded Period

Arm description

Subjects received placebo (normal saline solution of 0.9 percent [%] sodium chloride) intramuscularly.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Normal saline solution of 0.9 percent [%] sodium chloride

Number of subjects in period 2	SSA: BNT162b2 30 microgram: Blinded and Open Label Period	SSA: Placebo: Blinded Period
Started	4544	4906
Completed	3272	73
Not completed	1272	4833
Adverse event, serious fatal	5	-
Withdrawn by parent/guardian	1	-
Physician decision	2	3
Consent withdrawn by subject	135	109
Adverse event, non-fatal	1	-
No longer meets eligibility criteria	20	11
Refused further study procedures	1	1
Pregnancy	-	1
Subjects received BNT162b2 30 microgram	-	4430
Unspecified	621	13
Lost to follow-up	109	34
Protocol deviation	377	231

Period 3 title

SSA: OL: Placebo then BNT162b2 30 mcg

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

SSA: Placebo then BNT162b2 (30 microgram): Open-Label Period

Arm description

Subjects received placebo (normal saline solution of 0.9 percent [%] sodium chloride) intramuscularly and then one dose (30 microgram) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Normal saline solution of 0.9 percent [%] sodium chloride

Investigational medicinal product name

BNT162b2

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

30 microgram administered intramuscularly

Number of subjects in period 3	SSA: Placebo then BNT162b2 (30 microgram): Open-Label Period
Started	4430
Completed	3878
Not completed	552
Adverse event, serious fatal	5
Consent withdrawn by subject	25
No longer meets eligibility criteria	4
Unspecified	429
Lost to follow-up	41
Protocol deviation	48

Baseline characteristics

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Reporting group title

SSA: BNT162b2 30 mcg: Blinded and Open Label Period

Reporting group description

Subjects received one dose (30 microgram) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSA: Placebo: Blinded Period

Reporting group description

Subjects received placebo (normal saline solution of 0.9 percent [%] sodium chloride) intramuscularly.

Reporting group title

SSB: BNT162b2 30 mcg then Placebo

Reporting group description

Reporting group title

SSB: Placebo then BNT162b2 30 mcg

Reporting group description

Reporting group title

SSF: BNT162b2 30 mcg

Reporting group description

Subjects received one dose (30 mcg) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 60 mcg

Reporting group description

Subjects received one dose (60 mcg) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 OMI 30 mcg

Reporting group description

Subjects received one dose (30 mcg) of BNT162b2 Omicron (OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 OMI 60 mcg

Reporting group description

Subjects received one dose (60 mcg) of BNT162b2 Omicron (OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Reporting group description

Subjects received a total of 30 mcg BNT162b2 (15 mcg BNT162b2 and 15 mcg BNT162b2 OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Reporting group description

Subjects received a total of 60 mcg BNT162b2 (30 mcg BNT162b2 and 30 mcg BNT162b2 OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group values	SSA: BNT162b2 30 mcg: Blinded and Open Label Period	SSA: Placebo: Blinded Period	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg	Total
Number of subjects	5080	5041	753	732	21	19	21	20	20	21	11728
Age Categorical
Units: Subjects
In utero	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
Newborns (0-27 days)	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
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	46	44	233	228	0	0	0	0	0	0	551
Adults (18-64 years)	3859	3811	520	504	6	7	6	8	9	9	8739
From 65-84 years	1166	1174	0	0	15	12	15	12	11	12	2417
85 years and over	9	12	0	0	0	0	0	0	0	0	21
Age Continuous
Units: years
arithmetic mean (standard deviation)	51.8 ( 15.24 )	51.7 ( 15.33 )	21.4 ( 5.29 )	21.4 ( 5.38 )	68.4 ( 6.09 )	66.9 ( 4.75 )	68.1 ( 4.86 )	67.2 ( 5.70 )	66.7 ( 4.88 )	66.0 ( 3.65 )	-
Gender Categorical
Units: Subjects
Female	2624	2526	434	447	9	9	13	10	8	12	6092
Male	2456	2515	319	285	12	10	8	10	12	9	5636
Race
Units: Subjects
White	3998	4002	491	493	21	19	21	20	20	21	9106
Black or African American	470	457	159	155	0	0	0	0	0	0	1241
American Indian or Alaska Native	86	92	4	6	0	0	0	0	0	0	188
Asian	288	269	61	58	0	0	0	0	0	0	676
Native Hawaiian or other Pacific Islander	7	11	1	1	0	0	0	0	0	0	20
Multiracial	209	197	24	12	0	0	0	0	0	0	442
Not reported	22	13	13	7	0	0	0	0	0	0	55
Ethnicity
Units: Subjects
Hispanic/Latino	759	750	152	150	0	0	0	0	0	0	1811
Non-Hispanic/non-Latino	4309	4283	595	577	21	19	21	20	19	21	9885
Not reported	12	8	6	5	0	0	0	0	1	0	32

End points

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Reporting group title

SSA: BNT162b2 30 mcg: Blinded and Open Label Period

Reporting group description

Subjects received one dose (30 microgram) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSA: Placebo: Blinded Period

Reporting group description

Subjects received placebo (normal saline solution of 0.9 percent [%] sodium chloride) intramuscularly.

Reporting group title

SSB: BNT162b2 30 mcg then Placebo

Reporting group description

Reporting group title

SSB: Placebo then BNT162b2 30 mcg

Reporting group description

Reporting group title

SSF: BNT162b2 30 mcg

Reporting group description

Subjects received one dose (30 mcg) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 60 mcg

Reporting group description

Subjects received one dose (60 mcg) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 OMI 30 mcg

Reporting group description

Subjects received one dose (30 mcg) of BNT162b2 Omicron (OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 OMI 60 mcg

Reporting group description

Subjects received one dose (60 mcg) of BNT162b2 Omicron (OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Reporting group description

Subjects received a total of 30 mcg BNT162b2 (15 mcg BNT162b2 and 15 mcg BNT162b2 OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Reporting group description

Subjects received a total of 60 mcg BNT162b2 (30 mcg BNT162b2 and 30 mcg BNT162b2 OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSA: BNT162b2 30 microgram: Blinded and Open Label Period

Reporting group description

Subjects received one dose (30 microgram) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSA: Placebo: Blinded Period

Reporting group description

Subjects received placebo (normal saline solution of 0.9 percent [%] sodium chloride) intramuscularly.

Reporting group title

SSA: Placebo then BNT162b2 (30 microgram): Open-Label Period

Reporting group description

Subject analysis set title

SSA: Original Placebo/BNT162b2 30 mcg: Open Label Period

Subject analysis set type

Safety analysis

Subject analysis set description

Primary: SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population

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End point title

SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population ^[1]

End point description

Occurrences of first COVID-19 infection in subjects after booster dose without past SARS-CoV-2 infection at interim analysis were reported in this end point. Evaluable efficacy population included all eligible randomised subjects who received the booster vaccination as randomised and had no other important protocol deviations as determined by the clinician. Human Immunodeficiency Virus (HIV) positive subjects were excluded from this analysis. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From 7 Days after booster vaccination (Surveillance time [1000 person-year]: BNT162b2- 0.823, Placebo- 0.792)

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

End point values	SSA: BNT162b2 30 mcg: Blinded and Open Label Period	SSA: Placebo: Blinded Period
Number of subjects analysed	4659	4614
Units: Number of cases
number (not applicable)	6	123

BNT162b2 30 mcg versus Placebo

Statistical analysis description

2-Sided CI for Relative vaccine efficacy (RVE) is derived based on the Clopper and Pearson method adjusted for surveillance time.

Comparison groups

SSA: BNT162b2 30 mcg: Blinded and Open Label Period v SSA: Placebo: Blinded Period

Number of subjects included in analysis

9273

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Surveillance Time

Point estimate

95.3

Confidence interval

level

95%

sides

2-sided

lower limit

89.5

upper limit

98.3

Primary: SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population

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End point title

SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population ^[2]

End point description

Occurrences of first COVID-19 infection in subjects after booster dose with and without past SARS-CoV-2 infection at interim analysis were reported in this end point. Evaluable efficacy population included all eligible randomised subjects who received the booster vaccination as randomised and had no other important protocol deviations as determined by the clinician. HIV positive subjects were excluded from this analysis. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From 7 Days after booster vaccination (Surveillance time [1000 person-year]: BNT162b2- 0.871, Placebo- 0.835)

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSA: BNT162b2 30 mcg: Blinded and Open Label Period	SSA: Placebo: Blinded Period
Number of subjects analysed	4934	4863
Units: Number of cases
number (not applicable)	7	124

BNT162b2 30 mcg versus Placebo

Statistical analysis description

2-Sided CI for RVE is derived based on the Clopper and Pearson method adjusted for surveillance time.

Comparison groups

SSA: BNT162b2 30 mcg: Blinded and Open Label Period v SSA: Placebo: Blinded Period

Number of subjects included in analysis

9797

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Surveillance Time

Point estimate

94.6

Confidence interval

level

95%

sides

2-sided

lower limit

88.5

upper limit

97.9

Primary: SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population

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End point title

SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population ^[3]

End point description

Occurrences of first COVID-19 infection in subjects after booster dose without past SARS-CoV-2 infection at final analysis were reported in this end point. Evaluable efficacy population included all eligible randomised subjects who received the booster vaccination as randomised and had no other important protocol deviations as determined by the clinician. HIV positive subjects were excluded from this analysis. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From 7 Days after booster vaccination (Surveillance time [1000 person-year]: BNT162b2- 1.098, Placebo- 0.932)

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

End point values	SSA: BNT162b2 30 mcg: Blinded and Open Label Period	SSA: Placebo: Blinded Period
Number of subjects analysed	4639	4601
Units: Number of cases
number (not applicable)	63	148

BNT162b2 30 mcg versus Placebo

Statistical analysis description

2-Sided CI for Relative Vaccine Efficacy (RVE) is derived based on the Clopper and Pearson method adjusted for surveillance time.

Comparison groups

SSA: BNT162b2 30 mcg: Blinded and Open Label Period v SSA: Placebo: Blinded Period

Number of subjects included in analysis

9240

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Surveillance Time

Point estimate

63.9

Confidence interval

level

95%

sides

2-sided

lower limit

51.1

upper limit

73.5

Primary: SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population

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End point title

SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population ^[4]

End point description

Occurrences of first COVID-19 infection in subjects after booster dose with and without past SARS-CoV-2 infection at final analysis were reported in this end point. Evaluable efficacy population included all eligible randomised subjects who received the booster vaccination as randomised and had no other important protocol deviations as determined by the clinician. HIV positive subjects were excluded from this analysis. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From 7 Days after booster vaccination (Surveillance time [1000 person-year]: BNT162b2- 1.173, Placebo- 0.989)

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSA: BNT162b2 30 mcg: Blinded and Open Label Period	SSA: Placebo: Blinded Period
Number of subjects analysed	4903	4846
Units: Number of cases
number (not applicable)	67	150

BNT162b2 30 mcg versus Placebo

Statistical analysis description

2-Sided CI for RVE is derived based on the Clopper and Pearson method adjusted for surveillance time.

Comparison groups

SSA: BNT162b2 30 mcg: Blinded and Open Label Period v SSA: Placebo: Blinded Period

Number of subjects included in analysis

9749

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Surveillance Time

Point estimate

62.4

Confidence interval

level

95%

sides

2-sided

lower limit

49.5

upper limit

72.2

Primary: SSA: Percentage of Subjects Reporting Adverse Events

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End point title

SSA: Percentage of Subjects Reporting Adverse Events ^[5] ^[6]

End point description

An AE was any untoward medical occurrence in a subject temporally associated with the use of study intervention, whether or not considered related to the study intervention. Safety population included all randomised subjects who received at least 1 dose of the study intervention. HIV positive subjects were excluded from this analysis. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From booster dose to 1 month after booster dose (Day 1)

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
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSA: BNT162b2 30 mcg: Blinded and Open Label Period	SSA: Placebo: Blinded Period
Number of subjects analysed	5054	5016
Units: Percentage of subjects
number (confidence interval 95%)	26.3 (25.0 to 27.5)	7.1 (6.4 to 7.8)

No statistical analyses for this end point

Primary: SSA: Percentage of Subjects Reporting Serious Adverse Events

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End point title

SSA: Percentage of Subjects Reporting Serious Adverse Events ^[7] ^[8]

End point description

An SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening (immediate risk of death); required inpatient hospitalisation or prolongation of existing hospitalisation; persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect; or that was considered as an important medical event. Safety population included all randomised subjects who received at least 1 dose of the study intervention. HIV positive subjects were excluded from this analysis. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From BNT162b2 dose to 6 months after BNT162b2 dose for original BNT162b2 and original placebo/BNT162b2 groups, from placebo dose to unblinding for original placebo group. Median blinded follow-up period for original placebo subjects was 2.8 months

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
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSA: BNT162b2 30 mcg: Blinded and Open Label Period	SSA: Placebo: Blinded Period	SSA: Original Placebo/BNT162b2 30 mcg: Open Label Period
Number of subjects analysed	5054	5016	4405
Units: Percentage of subjects
number (confidence interval 95%)	1.4 (1.1 to 1.8)	0.8 (0.6 to 1.1)	1.0 (0.7 to 1.3)

No statistical analyses for this end point

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level pre-Dose; Vaccination 1

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End point title

SSB: Percentage of Subjects With Elevated Troponin I Level pre-Dose; Vaccination 1 ^[9] ^[10]

End point description

Percentage of subjects with elevated troponin I levels before administration of Vaccination 1 were reported in this endpoint. Safety population included all subjects who received at least 1 dose of the study intervention. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Pre-dose on Day 1 (Vaccination 1)

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
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg
Number of subjects analysed	751	730
Units: Percentage of subjects
number (confidence interval 95%)	0.7 (0.2 to 1.5)	0.5 (0.1 to 1.4)

No statistical analyses for this end point

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level Within 5 Days After Vaccination 1

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End point title

SSB: Percentage of Subjects With Elevated Troponin I Level Within 5 Days After Vaccination 1 ^[11] ^[12]

End point description

Percentage of subjects with elevated troponin I levels within 5 days after administration of Vaccination 1 were reported in this endpoint. Safety population included all subjects who received at least 1 dose of the study intervention. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Within 5 days after Vaccination 1

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
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg
Number of subjects analysed	719	693
Units: Percentage of subjects
number (confidence interval 95%)	1.0 (0.4 to 2.0)	0.6 (0.2 to 1.5)

No statistical analyses for this end point

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level pre-Vaccination 2 (1 Month After Vaccination 1)

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End point title

SSB: Percentage of Subjects With Elevated Troponin I Level pre-Vaccination 2 (1 Month After Vaccination 1) ^[13] ^[14]

End point description

Percentage of subjects with elevated troponin I levels pre vaccination 2 were reported in this endpoint. Safety population included all subjects who received at least 1 dose of the study intervention. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Pre-Vaccination 2 (1 month after Vaccination 1)

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
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg
Number of subjects analysed	628	600
Units: Percentage of Subjects
number (confidence interval 95%)	1.1 (0.4 to 2.3)	0.3 (0.0 to 1.2)

No statistical analyses for this end point

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level 1 Month After Vaccination 2

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End point title

SSB: Percentage of Subjects With Elevated Troponin I Level 1 Month After Vaccination 2 ^[15] ^[16]

End point description

Percentage of subjects with elevated troponin I levels within 1 month after administration of Vaccination 2 were reported in this endpoint. Safety population included all subjects who received at least 1 dose of the study intervention. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

1 month after Vaccination 2

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
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg
Number of subjects analysed	676	645
Units: Percentage of subjects
number (confidence interval 95%)	0.7 (0.2 to 1.7)	0.3 (0.0 to 1.1)

No statistical analyses for this end point

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level Within 5 Days After Vaccination 2

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End point title

SSB: Percentage of Subjects With Elevated Troponin I Level Within 5 Days After Vaccination 2 ^[17] ^[18]

End point description

Percentage of subjects with elevated troponin I levels within 5 days after administration of Vaccination 2 were reported in this endpoint. Safety population included all subjects who received at least 1 dose of the study intervention. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Within 5 days after vaccination 2

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
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg
Number of subjects analysed	667	634
Units: Percentage of subjets
number (confidence interval 95%)	1.5 (0.7 to 2.7)	0.3 (0.0 to 1.1)

No statistical analyses for this end point

Primary: SSB: Percentage of Subjects With Local Reactions Within 7 Days After Vaccination 1

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End point title

SSB: Percentage of Subjects With Local Reactions Within 7 Days After Vaccination 1 ^[19] ^[20]

End point description

Local reactions recorded by subjects in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (cm) and were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit or hospitalisation for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of subjects reporting local reactions after Vaccination 1 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented. Safety population = all subjects receiving at least 1 dose of study intervention. Here, 'Number of Subjects Analysed' (N) = subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after Vaccination 1

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
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg
Number of subjects analysed	747	728
Units: Percentage of subjects
number (confidence interval 95%)
Redness: Any	5.8 (4.2 to 7.7)	0.5 (0.1 to 1.4)
Redness: Mild	4.4 (3.1 to 6.1)	0.4 (0.1 to 1.2)
Redness: Moderate	1.1 (0.5 to 2.1)	0.1 (0.0 to 0.8)
Redness: Severe	0.3 (0.0 to 1.0)	0 (0.0 to 0.5)
Redness: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Swelling: Any	6.6 (4.9 to 8.6)	0.5 (0.1 to 1.4)
Swelling: Mild	5.0 (3.5 to 6.8)	0.4 (0.1 to 1.2)
Swelling: Moderate	1.5 (0.7 to 2.6)	0 (0.0 to 0.5)
Swelling: Severe	0.1 (0.0 to 0.7)	0.1 (0.0 to 0.8)
Swelling: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Pain at injection site: Any	74.4 (71.1 to 77.5)	13.9 (11.4 to 16.6)
Pain at injection site: Mild	48.7 (45.1 to 52.4)	12.2 (9.9 to 14.8)
Pain at injection site: Moderate	25.4 (22.3 to 28.7)	1.6 (0.9 to 2.9)
Pain at injection site: Severe	0.3 (0.0 to 1.0)	0 (0.0 to 0.5)
Pain at injection site: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)

No statistical analyses for this end point

Primary: SSB: Percentage of Subjects With Local Reactions Within 7 Days After Vaccination 2

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End point title

SSB: Percentage of Subjects With Local Reactions Within 7 Days After Vaccination 2 ^[21] ^[22]

End point description

Local reactions recorded by subjects in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (cm) and were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (necrosis [swelling] or necrosis or exfoliative dermatitis [redness]). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (emergency room [ER] visit or hospitalisation for severe pain at injection site). Grade 4 were classified by investigator or medically qualified person. Percentage of subjects reporting local reactions after Vaccination 2 and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented. Safety population = all subjects receiving at least 1 dose of study intervention. Here, 'Number of Subjects Analysed' (N) = subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after Vaccination 2

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
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg
Number of subjects analysed	706	672
Units: Percentage of subjects
number (confidence interval 95%)
Redness: Any	0.7 (0.2 to 1.6)	4.6 (3.2 to 6.5)
Redness: Mild	0.3 (0.0 to 1.0)	2.8 (1.7 to 4.4)
Redness: Moderate	0.4 (0.1 to 1.2)	1.5 (0.7 to 2.7)
Redness: Severe	0 (0.0 to 0.5)	0.3 (0.0 to 1.1)
Redness: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Swelling: Any	0.4 (0.1 to 1.2)	5.5 (3.9 to 7.5)
Swelling: Mild	0.4 (0.1 to 1.2)	3.4 (2.2 to 5.1)
Swelling: Moderate	0 (0.0 to 0.5)	1.9 (1.0 to 3.3)
Swelling: Severe	0 (0.0 to 0.5)	0.1 (0.0 to 0.8)
Swelling: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Pain at injection site: Any	8.8 (6.8 to 11.1)	71.7 (68.2 to 75.1)
Pain at injection site: Mild	6.7 (4.9 to 8.8)	40.3 (36.6 to 44.1)
Pain at injection site: Moderate	2.1 (1.2 to 3.5)	30.5 (27.0 to 34.1)
Pain at injection site: Severe	0 (0.0 to 0.5)	0.9 (0.3 to 1.9)
Pain at injection site: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)

No statistical analyses for this end point

Primary: SSB: Percentage of Subjects With Systemic Events Within 7 Days After Vaccination 1

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End point title

SSB: Percentage of Subjects With Systemic Events Within 7 Days After Vaccination 1 ^[23] ^[24]

End point description

Systemic events recorded in e-diary. Fever: oral temperature greater than or equal to (>=) 38.0 degree Celsius (deg C) and categorised as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C and >40.0 deg C. Fatigue, headache, chills, nausea, new or worsened muscle pain and new or worsened joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit/hospitalisation). Vomiting: mild: 1-2 times in 24 hours (h), moderate: >2 times in 24h, severe: required intravenous hydration and Grade 4: ER visit/hospitalisation for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit/hospitalisation for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method. Safety population, ‘N’=subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after Vaccination 1

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: No statistical analysis was planned for this endpoint

End point values	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg
Number of subjects analysed	747	728
Units: Percentage of subjects
number (confidence interval 95%)
Fever: >=38 deg C	6.0 (4.4 to 8.0)	1.9 (1.1 to 3.2)
Fever: 38.0 to 38.4 deg C	4.1 (2.8 to 5.8)	1.4 (0.7 to 2.5)
Fever: >38.4 to 38.9 deg C	1.7 (0.9 to 3.0)	0.3 (0.0 to 1.0)
Fever: >38.9 to 40.0 deg C	0.1 (0.0 to 0.7)	0.3 (0.0 to 1.0)
Fever: >40.0 deg C	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Fatigue: Any	54.2 (50.6 to 57.8)	31.9 (28.5 to 35.4)
Fatigue: Mild	27.4 (24.3 to 30.8)	19.5 (16.7 to 22.6)
Fatigue: Moderate	25.3 (22.2 to 28.6)	12.2 (9.9 to 14.8)
Fatigue: Severe	1.5 (0.7 to 2.6)	0.1 (0.0 to 0.8)
Fatigue: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Headache: Any	42.6 (39.0 to 46.2)	28.3 (25.0 to 31.7)
Headache: Mild	24.2 (21.2 to 27.5)	18.0 (15.3 to 21.0)
Headache: Moderate	17.3 (14.6 to 20.2)	10.0 (7.9 to 12.4)
Headache: Severe	1.1 (0.5 to 2.1)	0.3 (0.0 to 1.0)
Headache: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Chills: Any	17.1 (14.5 to 20.0)	5.9 (4.3 to 7.9)
Chills: Mild	10.6 (8.5 to 13.0)	4.4 (3.0 to 6.1)
Chills: Moderate	6.3 (4.7 to 8.3)	1.5 (0.8 to 2.7)
Chills: Severe	0.3 (0.0 to 1.0)	0 (0.0 to 0.5)
Chills: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Vomiting: Any	3.2 (2.1 to 4.7)	0.8 (0.3 to 1.8)
Vomiting: Mild	2.8 (1.7 to 4.3)	0.7 (0.2 to 1.6)
Vomiting: Moderate	0.4 (0.1 to 1.2)	0.1 (0.0 to 0.8)
Vomiting: Severe	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Vomiting: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Diarrhea: Any	7.4 (5.6 to 9.5)	7.4 (5.6 to 9.6)
Diarrhea: Mild	6.4 (4.8 to 8.4)	6.0 (4.4 to 8.0)
Diarrhea: Moderate	0.9 (0.4 to 1.9)	1.4 (0.7 to 2.5)
Diarrhea: Severe	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Diarrhea: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
New or worsened muscle pain: Any	27.6 (24.4 to 30.9)	7.7 (5.9 to 9.9)
New or worsened muscle pain: Mild	14.1 (11.6 to 16.8)	5.1 (3.6 to 6.9)
New or worsened muscle pain: Moderate	13.3 (10.9 to 15.9)	2.5 (1.5 to 3.9)
New or worsened muscle pain: Severe	0.3 (0.0 to 1.0)	0.1 (0.0 to 0.8)
New or worsened muscle pain: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
New or worsened joint pain: Any	12.9 (10.5 to 15.5)	4.5 (3.1 to 6.3)
New or worsened joint pain: Mild	8.3 (6.4 to 10.5)	3.0 (1.9 to 4.5)
New or worsened joint pain: Moderate	4.3 (2.9 to 6.0)	1.5 (0.8 to 2.7)
New or worsened joint pain: Severe	0.3 (0.0 to 1.0)	0 (0.0 to 0.5)
New or worsened joint pain: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)

No statistical analyses for this end point

Primary: SSB: Percentage of Subjects With Systemic Events Within 7 Days After Vaccination 2

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End point title

SSB: Percentage of Subjects With Systemic Events Within 7 Days After Vaccination 2 ^[25] ^[26]

End point description

End point type

Primary

End point timeframe

Day 1 up to Day 7 after Vaccination 2

Notes
[25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg
Number of subjects analysed	706	672
Units: Percentage of subjects
number (confidence interval 95%)
Fever: >=38 deg C	0.4 (0.1 to 1.2)	4.3 (2.9 to 6.1)
Fever: 38.0 to 38.4 deg C	0.3 (0.0 to 1.0)	2.5 (1.5 to 4.0)
Fever: >38.4 to 38.9 deg C	0.1 (0.0 to 0.8)	1.3 (0.6 to 2.5)
Fever: >38.9 to 40.0 deg C	0 (0.0 to 0.5)	0.4 (0.1 to 1.3)
Fever: >40.0 deg C	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Fatigue: Any	17.6 (14.8 to 20.6)	47.3 (43.5 to 51.2)
Fatigue: Mild	8.6 (6.7 to 11.0)	18.8 (15.9 to 21.9)
Fatigue: Moderate	8.5 (6.5 to 10.8)	27.1 (23.8 to 30.6)
Fatigue: Severe	0.4 (0.1 to 1.2)	1.5 (0.7 to 2.7)
Fatigue: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Headache: Any	17.8 (15.1 to 20.9)	39.7 (36.0 to 43.5)
Headache: Mild	10.3 (8.2 to 12.8)	19.8 (16.8 to 23.0)
Headache: Moderate	7.2 (5.4 to 9.4)	19.0 (16.1 to 22.2)
Headache: Severe	0.3 (0.0 to 1.0)	0.9 (0.3 to 1.9)
Headache: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Chills: Any	3.7 (2.4 to 5.3)	22.3 (19.2 to 25.7)
Chills: Mild	2.3 (1.3 to 3.7)	13.2 (10.8 to 16.0)
Chills: Moderate	1.1 (0.5 to 2.2)	8.8 (6.8 to 11.2)
Chills: Severe	0.3 (0.0 to 1.0)	0.3 (0.0 to 1.1)
Chills: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Vomiting: Any	1.0 (0.4 to 2.0)	1.9 (1.0 to 3.3)
Vomiting: Mild	0.7 (0.2 to 1.6)	1.8 (0.9 to 3.1)
Vomiting: Moderate	0.3 (0.0 to 1.0)	0.1 (0.0 to 0.8)
Vomiting: Severe	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Vomiting: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Diarrhea: Any	3.3 (2.1 to 4.8)	8.0 (6.1 to 10.4)
Diarrhea: Mild	2.1 (1.2 to 3.5)	6.5 (4.8 to 8.7)
Diarrhea: Moderate	1.1 (0.5 to 2.2)	1.5 (0.7 to 2.7)
Diarrhea: Severe	0 (0.0 to 0.5)	0 (0.0 to 0.5)
Diarrhea: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
New or worsened muscle pain: Any	4.5 (3.1 to 6.3)	29.2 (25.8 to 32.8)
New or worsened muscle pain: Mild	2.3 (1.3 to 3.7)	15.9 (13.2 to 18.9)
New or worsened muscle pain: Moderate	2.1 (1.2 to 3.5)	12.9 (10.5 to 15.7)
New or worsened muscle pain: Severe	0.1 (0.0 to 0.8)	0.3 (0.0 to 1.1)
New or worsened muscle pain: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)
New or worsened joint pain: Any	3.1 (2.0 to 4.7)	12.2 (9.8 to 14.9)
New or worsened joint pain: Mild	1.6 (0.8 to 2.8)	7.4 (5.6 to 9.7)
New or worsened joint pain: Moderate	1.6 (0.8 to 2.8)	4.8 (3.3 to 6.7)
New or worsened joint pain: Severe	0 (0.0 to 0.5)	0 (0.0 to 0.5)
New or worsened joint pain: Grade 4	0 (0.0 to 0.5)	0 (0.0 to 0.5)

No statistical analyses for this end point

Primary: SSB: Percentage of Subjects Reporting Adverse Events (AEs) 1 Month After Vaccination 1

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End point title

SSB: Percentage of Subjects Reporting Adverse Events (AEs) 1 Month After Vaccination 1 ^[27] ^[28]

End point description

An AE was defined as any untoward medical occurrence in a clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of subjects reporting AEs within 1 month after Vaccination 1 were reported in this endpoint. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this endpoint. Safety population included all subjects who received at least 1 dose of the study intervention.

End point type

Primary

End point timeframe

Vaccination 1 up to 1 Month After Vaccination 1

Notes
[27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg
Number of subjects analysed	753	732
Units: Percentage of subjects
number (confidence interval 95%)	9.4 (7.4 to 11.7)	10.4 (8.3 to 12.8)

No statistical analyses for this end point

Primary: SSB: Percentage of Subjects Reporting Adverse Events (AEs) 1 Month After Vaccination 2

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End point title

SSB: Percentage of Subjects Reporting Adverse Events (AEs) 1 Month After Vaccination 2 ^[29] ^[30]

End point description

An AE was defined as any untoward medical occurrence in a clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of subjects reporting AEs within 1 month after Vaccination 2 were reported in this endpoint. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this endpoint. Safety population included all subjects who received at least 1 dose of the study intervention. Subjects who did not receive Vaccination 2 or who received an incorrect vaccine at Vaccination 2 were excluded from this analysis. Here, ‘Number of Subjects Analysed’ signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Vaccination 2 up to 1 month after Vaccination 2

Notes
[29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg
Number of subjects analysed	731	700
Units: Percentage of subjects
number (confidence interval 95%)	5.6 (4.1 to 7.5)	7.4 (5.6 to 9.6)

No statistical analyses for this end point

Primary: SSB: Percentage of Subjects Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 1

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End point title

SSB: Percentage of Subjects Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 1 ^[31] ^[32]

End point description

An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening; resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalisation or prolongation of existing hospitalisation. Exact 2-sided 95% CI was based on the Clopper and Pearson method. Safety population included all subjects who received at least 1 dose of the study intervention.

End point type

Primary

End point timeframe

Vaccination 1 up to 1 month after Vaccination 1

Notes
[31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg
Number of subjects analysed	753	732
Units: Percentage of subjects
number (confidence interval 95%)	0.1 (0.0 to 0.7)	0.3 (0.0 to 1.0)

No statistical analyses for this end point

Primary: SSB: Percentage of Subjects Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 2

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End point title

SSB: Percentage of Subjects Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 2 ^[33] ^[34]

End point description

End point type

Primary

End point timeframe

Vaccination 2 up to 1 month after Vaccination 2

Notes
[33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSB: BNT162b2 30 mcg then Placebo	SSB: Placebo then BNT162b2 30 mcg
Number of subjects analysed	731	700
Units: Percentage of subjects
number (confidence interval 95%)	0 (0.0 to 0.5)	0.1 (0.0 to 0.8)

No statistical analyses for this end point

Primary: SSF: Percentage of Subjects With Local Reactions Within 7 Days After Study Vaccination

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End point title

SSF: Percentage of Subjects With Local Reactions Within 7 Days After Study Vaccination ^[35] ^[36]

End point description

Local reactions were recorded by subjects in e-diary. Redness and swelling were measured and recorded in measuring device units (mdu) where, 1 mdu =0.5 centimeter (cm) and were graded as mild (greater than [>] 2.0 to 5.0 cm), moderate (>5.0 to 10.0 cm), severe (>10.0 cm) and Grade 4 (emergency room [ER] visit or hospitalisation for severe pain). Pain at injection site was graded as mild (did not interfere with activity), moderate (interfered with activity), severe (prevented daily activity) and Grade 4 (necrosis [swelling] or necrosis/exfoliative dermatitis [redness]). Grade 4 were classified by investigator or medically qualified person. Percentage of subjects reporting local reactions after study vaccination and associated 2-sided 95% confidence interval (CI) based on Clopper and Pearson method was presented. Safety population included all subjects receiving at least 1 dose of study intervention. Here, 'Number of Subjects Analysed (N)' = subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after the study vaccination

Notes
[35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	19	21	20	20	21
Units: Percentage of subjects
number (confidence interval 95%)
Redness: Any	19.0 (5.4 to 41.9)	21.1 (6.1 to 45.6)	23.8 (8.2 to 47.2)	20.0 (5.7 to 43.7)	10.0 (1.2 to 31.7)	28.6 (11.3 to 52.2)
Redness: Mild	4.8 (0.1 to 23.8)	10.5 (1.3 to 33.1)	14.3 (3.0 to 36.3)	5.0 (0.1 to 24.9)	5.0 (0.1 to 24.9)	23.8 (8.2 to 47.2)
Redness: Moderate	14.3 (3.0 to 36.3)	10.5 (1.3 to 33.1)	9.5 (1.2 to 30.4)	10.0 (1.2 to 31.7)	5.0 (0.1 to 24.9)	4.8 (0.1 to 23.8)
Redness: Severe	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	5.0 (0.1 to 24.9)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Redness: Grade 4	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Swelling: Any	14.3 (3.0 to 36.3)	15.8 (3.4 to 39.6)	14.3 (3.0 to 36.3)	15.0 (3.2 to 37.9)	15.0 (3.2 to 37.9)	28.6 (11.3 to 52.2)
Swelling: Mild	4.8 (0.1 to 23.8)	5.3 (0.1 to 26.0)	4.8 (0.1 to 23.8)	5.0 (0.1 to 24.9)	5.0 (0.1 to 24.9)	23.8 (8.2 to 47.2)
Swelling: Moderate	9.5 (1.2 to 30.4)	10.5 (1.3 to 33.1)	9.5 (1.2 to 30.4)	10.0 (1.2 to 31.7)	10.0 (1.2 to 31.7)	4.8 (0.1 to 23.8)
Swelling: Severe	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Swelling: Grade 4	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Pain at the injection site: Any	71.4 (47.8 to 88.7)	94.7 (74.0 to 99.9)	90.5 (69.6 to 98.8)	80.0 (56.3 to 94.3)	75.0 (50.9 to 91.3)	90.5 (69.6 to 98.8)
Pain at the injection site: Mild	52.4 (29.8 to 74.3)	52.6 (28.9 to 75.6)	66.7 (43.0 to 85.4)	45.0 (23.1 to 68.5)	55.0 (31.5 to 76.9)	57.1 (34.0 to 78.2)
Pain at the injection site: Moderate	19.0 (5.4 to 41.9)	36.8 (16.3 to 61.6)	19.0 (5.4 to 41.9)	35.0 (15.4 to 59.2)	20.0 (5.7 to 43.7)	33.3 (14.6 to 57.0)
Pain at the injection site: Severe	0 (0.0 to 16.1)	5.3 (0.1 to 26.0)	4.8 (0.1 to 23.8)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Pain at the injection site: Grade 4	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)

No statistical analyses for this end point

Primary: SSF: Percentage of Subjects With Systemic Events Within 7 Days After Study Vaccination

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End point title

SSF: Percentage of Subjects With Systemic Events Within 7 Days After Study Vaccination ^[37] ^[38]

End point description

Systemic events recorded in e-diary. Fever:oral temperature greater than or equal to 38.0 deg C and categorised as >=38.0-38.4 deg C, >38.4-38.9 deg C, >38.9-40.0 deg C & >40.0 deg C. Fatigue, headache, chills, nausea, muscle pain and joint pain: mild (did not interfere with activity), moderate (some interference with activity), severe (prevented daily routine activity) and Grade 4 (ER visit or hospitalisation). Vomiting: mild: 1-2 times in 24 h, moderate: > 2 times in 24h, severe: required intravenous hydration and Grade 4: ER or hospitalisation for hypotensive shock. Diarrhea: mild: 2-3 loose stools in 24h, moderate: 4-5 loose stools in 24h, severe: 6 or more loose stools in 24h and Grade 4: ER visit or hospitalisation for severe diarrhea. Grade 4 were classified by investigator or medically qualified person. Exact 95% CI was based on Clopper and Pearson method. Safety population= all subjects receiving at least 1 dose of study intervention. N=subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 1 up to Day 7 after the study vaccination

Notes
[37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	19	21	20	20	21
Units: Percentage of Subjects
number (confidence interval 95%)
Fever: >= 38.0 deg C	9.5 (1.2 to 30.4)	10.5 (1.3 to 33.1)	9.5 (1.2 to 30.4)	10.0 (1.2 to 31.7)	5.0 (0.1 to 24.9)	4.8 (0.1 to 23.8)
Fever: >= 38.0 deg C to 38.4 deg C	9.5 (1.2 to 30.4)	5.3 (0.1 to 26.0)	4.8 (0.1 to 23.8)	5.0 (0.1 to 24.9)	0 (0.0 to 16.8)	4.8 (0.1 to 23.8)
Fever: >38.4 deg C to 38.9 deg C	0 (0.0 to 16.1)	5.3 (0.1 to 26.0)	0 (0.0 to 16.1)	5.0 (0.1 to 24.9)	5.0 (0.1 to 24.9)	0 (0.0 to 16.1)
Fever: >38.9 deg C to 40.0 deg C	0 (0.0 to 16.1)	0 (0.0 to 17.6)	4.8 (0.1 to 23.8)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Fever: >40.0 deg C	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Fatigue: Any	47.6 (25.7 to 70.2)	36.8 (16.3 to 61.6)	42.9 (21.8 to 66.0)	55.0 (31.5 to 76.9)	50.0 (27.2 to 72.8)	57.1 (34.0 to 78.2)
Fatigue: Mild	9.5 (1.2 to 30.4)	10.5 (1.3 to 33.1)	9.5 (1.2 to 30.4)	10.0 (1.2 to 31.7)	5.0 (0.1 to 24.9)	23.8 (8.5 to 47.2)
Fatigue: Moderate	23.8 (8.2 to 47.2)	21.1 (6.1 to 45.6)	28.6 (11.3 to 52.2)	35.0 (15.4 to 59.2)	40.0 (19.1 to 63.9)	33.3 (14.6 to 57.0)
Fatigue: Severe	14.3 (3.0 to 36.3)	5.3 (0.1 to 26.0)	4.8 (0.1 to 23.8)	10.0 (1.2 to 31.7)	5.0 (0.1 to 24.9)	0 (0.0 to 16.1)
Fatigue: Grade 4	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Headache: Any	28.6 (11.3 to 52.2)	26.3 (9.1 to 51.2)	23.8 (8.2 to 47.2)	55.0 (31.5 to 76.9)	35.0 (15.4 to 59.2)	38.1 (18.1 to 61.6)
Headache: Mild	19.0 (5.4 to 41.9)	15.8 (3.4 to 39.6)	4.8 (0.1 to 23.8)	15.0 (3.2 to 37.9)	20.0 (5.7 to 43.7)	19.0 (5.4 to 41.9)
Headache: Moderate	9.5 (1.2 to 30.4)	10.5 (1.3 to 33.1)	14.3 (3.0 to 36.3)	40.0 (19.1 to 63.9)	15.0 (3.2 to 37.9)	19.0 (5.4 to 41.9)
Headache: Severe	0 (0.0 to 16.1)	0 (0.0 to 17.6)	4.8 (0.1 to 23.8)	0 (0.0 to 16.8)	0 (0.0 to 16.7)	0 (0.0 to 16.1)
Headache: Grade 4	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Chills: Any	14.3 (3.0 to 36.3)	15.8 (3.4 to 39.6)	23.8 (8.2 to 47.2)	25.0 (8.7 to 49.1)	5.0 (0.1 to 24.9)	14.3 (3.0 to 36.3)
Chills: Mild	4.8 (0.1 to 23.8)	10.5 (1.3 to 33.1)	14.3 (3.0 to 36.3)	10.0 (1.2 to 31.7)	0 (0.0 to 16.8)	9.5 (1.2 to 30.4)
Chills: Moderate	9.5 (1.2 to 30.4)	5.3 (0.1 to 26.0)	4.8 (0.1 to 23.8)	5.0 (0.1 to 24.9)	5.0 (0.1 to 24.9)	4.8 (0.1 to 23.8)
Chills: Severe	0 (0.0 to 16.1)	0 (0.0 to 17.6)	4.8 (0.1 to 23.8)	10.0 (1.2 to 31.7)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Chills: Grade 4	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Vomiting: Any	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Vomiting: Mild	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Vomiting: Moderate	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Vomiting: Severe	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Vomiting: Grade 4	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Diarrhea: Any	14.3 (3.0 to 36.3)	5.3 (0.1 to 26.0)	9.5 (1.2 to 30.4)	5.0 (0.1 to 24.9)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Diarrhea: Mild	9.5 (1.2 to 30.4)	5.3 (0.1 to 26.0)	4.8 (0.1 to 23.8)	5.0 (0.1 to 24.9)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Diarrhea: Moderate	0 (0.0 to 16.1)	0 (0.0 to 17.6)	4.8 (0.1 to 23.8)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Diarrhea: Severe	4.8 (0.1 to 23.8)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
Diarrhea: Grade 4	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
New or worsened muscle pain: Any	19.0 (5.4 to 41.9)	42.1 (20.3 to 66.5)	23.8 (8.2 to 47.2)	30.0 (11.9 to 54.3)	25.0 (8.7 to 49.1)	28.6 (11.3 to 52.2)
New or worsened muscle pain: Mild	4.8 (0.1 to 23.8)	10.5 (1.3 to 33.1)	14.3 (3.0 to 36.3)	10.0 (1.2 to 31.9)	15.0 (3.2 to 37.9)	23.8 (8.2 to 47.2)
New or worsened muscle pain: Moderate	14.3 (3.0 to 36.3)	31.6 (12.6 to 56.6)	4.8 (0.1 to 23.8)	20.0 (5.7 to 43.7)	10.0 (1.2 to 31.7)	4.8 (0.1 to 23.8)
New or worsened muscle pain: Severe	0 (0.0 to 16.1)	0 (0.0 to 17.6)	4.8 (0.1 to 23.8)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
New or worsened muscle pain: Grade 4	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
New or worsened joint pain: Any	14.3 (3.0 to 36.3)	15.8 (3.4 to 39.6)	14.3 (3.0 to 36.3)	20.0 (5.7 to 43.7)	10.0 (1.2 to 31.7)	9.5 (1.2 to 30.4)
New or worsened joint pain: Mild	4.8 (0.1 to 23.8)	10.5 (1.3 to 33.1)	9.5 (1.2 to 30.4)	10.0 (1.2 to 31.7)	10.0 (1.2 to 31.7)	4.8 (0.1 to 23.8)
New or worsened joint pain: Moderate	9.5 (1.2 to 30.4)	5.3 (0.1 to 26.0)	4.8 (0.1 to 23.8)	10.0 (1.2 to 31.7)	0 (0.0 to 16.8)	4.8 (0.1 to 23.8)
New or worsened joint pain: Severe	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)
New or worsened joint pain: Grade 4	0 (0.0 to 16.1)	0 (0.0 to 17.6)	0 (0.0 to 16.1)	0 (0.0 to 16.8)	0 (0.0 to 16.8)	0 (0.0 to 16.1)

No statistical analyses for this end point

Primary: SSF: Percentage of Subjects Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination

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End point title

SSF: Percentage of Subjects Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination ^[39] ^[40]

End point description

An AE was defined as any untoward medical occurrence in a clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Percentage of subjects reporting AEs within 1 month after study vaccination were reported in this endpoint. Exact 2-sided CI was calculated using the Clopper and Pearson method. Only AEs collected by non-systematic assessment (i.e., excluding local reactions and systemic events) were reported in this endpoint. Safety population included all subjects who received at least 1 dose of the study intervention.

End point type

Primary

End point timeframe

From study vaccination up to 1 Month after study vaccination

Notes
[39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint
[40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	19	21	20	20	21
Units: Percentage of subjects
number (confidence interval 95%)	0 (0.0 to 16.1)	10.5 (1.3 to 33.1)	9.5 (1.2 to 30.4)	5.0 (0.1 to 24.9)	10.0 (1.2 to 31.7)	0 (0.0 to 16.1)

No statistical analyses for this end point

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

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End point title

SSF: Percentage of Subjects Reporting Serious Adverse Events (SAEs) Within 6 Months After Study Vaccination ^[41] ^[42]

End point description

End point type

Primary

End point timeframe

From study vaccination up to 6 Months after study vaccination

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
[42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	19	21	20	20	21
Units: Percentage of subjects
number (confidence interval 95%)	0 (0.0 to 16.1)	5.3 (0.1 to 26.0)	4.8 (0.1 to 23.8)	0 (0.0 to 16.8)	5.0 (0.1 to 24.9)	0 (0.0 to 16.1)

No statistical analyses for this end point

Primary: SSF: Geometric Mean Titer (GMTs) of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers Before Vaccination

Top of page

End point title

SSF: Geometric Mean Titer (GMTs) of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers Before Vaccination ^[43] ^[44]

End point description

GMT of SARS-CoV-2 Omicron BA.1 strain neutralizing titers before vaccination was reported in this endpoint. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination.

End point type

Primary

End point timeframe

Before vaccination (pre-vaccination)

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
[44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	19	21	20	20	21
Units: Titer
geometric mean (confidence interval 95%)	41.7 (22.4 to 77.4)	33.2 (17.6 to 62.6)	32.0 (17.0 to 60.1)	36.8 (17.5 to 77.1)	78.8 (29.3 to 211.6)	21.5 (14.2 to 32.7)

No statistical analyses for this end point

Primary: SSF: GMTs of SARS-CoV-2 Reference-Strain–Neutralizing Titers Before Vaccination

Top of page

End point title

SSF: GMTs of SARS-CoV-2 Reference-Strain–Neutralizing Titers Before Vaccination ^[45] ^[46]

End point description

GMT of SARS-CoV-2 reference-strain-neutralizing titers before vaccination was reported in this endpoint. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination.

End point type

Primary

End point timeframe

Before vaccination (pre-vaccination)

Notes
[45] - 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
[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: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	19	21	20	20	21
Units: Titer
geometric mean (confidence interval 95%)	541.1 (345.1 to 848.3)	382.4 (176.3 to 829.3)	437.5 (244.0 to 784.2)	315.2 (188.0 to 528.4)	803.4 (347.8 to 1855.8)	256.0 (135.1 to 485.0)

No statistical analyses for this end point

Primary: SSF: GMTs of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers Before Vaccination

Top of page

End point title

SSF: GMTs of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers Before Vaccination ^[47] ^[48]

End point description

GMT of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers before vaccination was reported in this endpoint. GMTs and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Before vaccination (pre-vaccination)

Notes
[47] - 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
[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: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	21	20	20	21
Units: Titer
geometric mean (confidence interval 95%)	27.1 (16.8 to 43.7)	18.0 (12.1 to 26.7)	20.2 (12.6 to 32.3)	23.4 (13.9 to 39.4)	42.2 (19.6 to 91.1)	15.0 (11.8 to 19.1)

No statistical analyses for this end point

Primary: SSF: GMT and Geometric Mean Ratios (GMR) of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers at Day 7

Top of page

End point title

SSF: GMT and Geometric Mean Ratios (GMR) of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers at Day 7 ^[49]

End point description

GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at Day 7 were reported in this endpoint in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. GMR was reported in the statistical analysis section. All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 7

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: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	21	20	20	20
Units: Titer
geometric mean (confidence interval 95%)	146.1 (102.5 to 208.2)	101.6 (48.6 to 212.6)	217.1 (97.8 to 481.9)	315.2 (164.6 to 603.5)	337.8 (133.8 to 852.7)	222.9 (125.7 to 395.1)

BNT162b2 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 [60 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 60 mcg v SSF: BNT162b2 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.79

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.56

BNT162b2 30 + BNT162b2 OMI 30 vs BNT162b2 30

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 [30 mcg] + BNT162b2 OMI [30 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

2.33

Confidence interval

level

95%

sides

2-sided

lower limit

1.2

upper limit

4.53

BNT162b2 15 + BNT162b2 OMI 15 vs BNT162b2 30

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 [15 mcg] + BNT162b2 OMI [15 mcg]- BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.49

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

2.89

BNT162b2 OMI 30 mcg vs BNT162b2 30 mcg

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 OMI [30 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 OMI 30 mcg v SSF: BNT162b2 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.93

upper limit

3.43

BNT162b2 OMI 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 OMI [60 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

2.35

Confidence interval

level

95%

sides

2-sided

lower limit

1.22

upper limit

4.55

Primary: SSF: GMT and GMR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Day 7

Top of page

End point title

SSF: GMT and GMR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Day 7 ^[50]

End point description

GMTs of SARS-CoV-2 reference strain neutralizing titers at Day 7 were reported in this endpoint in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. GMR was reported in the statistical analysis section. All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 7

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: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	21	20	20	20
Units: Titer
geometric mean (confidence interval 95%)	1917.2 (1153.8 to 3185.7)	1241.4 (624.3 to 2468.6)	1472.3 (855.4 to 2534.0)	1499.2 (838.6 to 2680.4)	2702.4 (1419.7 to 5143.8)	1845.8 (1087.4 to 3133.1)

BNT162b2 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.76

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.42

BNT162b2 OMI 30 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

1.58

BNT162b2 30 + BNT162b2 OMI 30 vs BNT162b2 30

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.35

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

2.5

BNT162b2 15 + BNT162b2 OMI 15 vs BNT162b2 30

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means BNT162b2 [15 mcg] + BNT162b2 OMI [15 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

2.09

BNT162b2 OMI 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.57

upper limit

1.95

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers at Day 7

Top of page

End point title

SSF: GMT and GMR of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers at Day 7 ^[51]

End point description

GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at Day 7 were reported in this endpoint in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. GMR was reported in the statistical analysis section. All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 7

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: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	17	21	20	20	21
Units: Titer
geometric mean (confidence interval 95%)	75.5 (52.7 to 108.0)	56.6 (32.1 to 99.8)	73.0 (38.7 to 137.9)	76.1 (46.0 to 125.9)	123.6 (63.8 to 239.5)	70.7 (48.5 to 103.0)

BNT162b2 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.58

upper limit

1.56

BNT162b2 30 + BNT162b2 OMI 30 vs BNT162b2 30

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.49

Confidence interval

level

95%

sides

2-sided

lower limit

0.94

upper limit

2.37

BNT162b2 15 + BNT162b2 OMI 15 vs BNT162b2 30

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 [15 mcg] + BNT162b2 OMI [15 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.84

BNT162b2 OMI 30 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.22

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

1.93

BNT162b2 OMI 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.8

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers at Month 1

Top of page

End point title

SSF: GMT and GMR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers at Month 1 ^[52]

End point description

GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at 1 month were reported in this endpoint in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. GMR was reported in the statistical analysis section. All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 1

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: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	20	20	20	20
Units: Titer
geometric mean (confidence interval 95%)	420.0 (252.2 to 699.5)	188.1 (88.9 to 398.2)	699.4 (398.9 to 1226.4)	675.6 (343.2 to 1329.8)	1024.0 (509.4 to 2058.3)	477.7 (236.0 to 967.1)

BNT162b2 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.49

Confidence interval

level

95%

sides

2-sided

lower limit

0.24

upper limit

1.03

BNT162b2 OMI 30 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

3.76

BNT162b2 30 + BNT162b2 OMI 30 vs BNT162b2 30

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.56

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

3.2

BNT162b2 15 + BNT162b2 OMI 15 vs BNT162b2 30

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 [15 mcg] + BNT162b2 OMI [15 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.85

upper limit

3.59

BNT162b2 OMI 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

3.5

Primary: SSF: GMT and GMR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Month 1

Top of page

End point title

SSF: GMT and GMR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Month 1 ^[53]

End point description

GMTs of SARS-CoV-2 reference strain neutralizing titers at 1 month were reported in this endpoint in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. GMR was reported in the statistical analysis section. All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 1

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: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	20	20	20	20
Units: Titer
geometric mean (confidence interval 95%)	4674.1 (3112.1 to 7020.2)	2048.4 (1007.8 to 4163.7)	3327.0 (1867.6 to 5926.9)	3565.8 (1992.1 to 6382.7)	5404.7 (3359.8 to 8694.1)	2521.4 (1388.9 to 4577.4)

BNT162b2 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.26

upper limit

0.95

BNT162b2 OMI 30 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.76

Confidence interval

level

95%

sides

2-sided

lower limit

0.41

upper limit

1.43

BNT162b2 30 + BNT162b2 OMI 30 vs BNT162b2 30

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.71

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

1.34

BNT162b2 15 + BNT162b2 OMI 15 vs BNT162b2 30

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 [15 mcg] + BNT162b2 OMI [15 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.96

Confidence interval

level

95%

sides

2-sided

lower limit

0.51

upper limit

1.8

BNT162b2 OMI 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.98

Confidence interval

level

95%

sides

2-sided

lower limit

0.52

upper limit

1.84

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers at Month 1

Top of page

End point title

SSF: GMT and GMR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers at Month 1 ^[54]

End point description

GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at 1 month were reported in this endpoint in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. GMR was reported in the statistical analysis section. All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 1

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: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	20	19	21	20	20	20
Units: Titer
geometric mean (confidence interval 95%)	157.6 (94.0 to 264.2)	85.7 (52.5 to 139.8)	151.0 (72.6 to 314.1)	230.7 (140.0 to 379.2)	284.0 (134.7 to 599.1)	147.0 (86.3 to 250.4)

BNT162b2 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.72

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

1.37

BNT162b2 30 + BNT162b2 OMI 30 vs BNT162b2 30

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.42

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

2.67

BNT162b2 15 + BNT162b2 OMI 15 vs BNT162b2 30

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 [15 mcg] + BNT162b2 OMI [15 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.28

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

2.39

BNT162b2 OMI 30 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.19

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

2.21

BNT162b2 OMI 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.63

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

3.02

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers at Month 3

Top of page

End point title

SSF: GMT and GMR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers at Month 3 ^[55]

End point description

GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at 3 months were reported in this endpoint in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. GMR was reported in the statistical analysis section. All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 3

Notes
[55] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	20	18	20	19	20	19
Units: Titer
geometric mean (confidence interval 95%)	247.3 (119.7 to 510.7)	118.5 (54.6 to 257.1)	461.4 (203.8 to 1044.7)	711.0 (388.8 to 1300.1)	512.0 (246.9 to 1061.6)	285.6 (132.8 to 614.1)

BNT162b2 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.52

Confidence interval

level

95%

sides

2-sided

lower limit

0.21

upper limit

1.25

BNT162b2 30 + BNT162b2 OMI 30 vs BNT162b2 30

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio

Point estimate

1.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

3.67

BNT162b2 15 + BNT162b2 OMI 15 vs BNT162b2 30

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 [15 mcg] + BNT162b2 OMI [15 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.52

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

3.62

BNT162b2 OMI 30 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

2.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.88

upper limit

4.88

BNT162b2 OMI 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

2.96

Confidence interval

level

95%

sides

2-sided

lower limit

1.24

upper limit

7.06

Primary: SSF: GMT and GMR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Month 3

Top of page

End point title

SSF: GMT and GMR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Month 3 ^[56]

End point description

GMTs of SARS-CoV-2 reference strain neutralizing titers at 3 months were reported in this endpoint in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. GMR was reported in the statistical analysis section. All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 3

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

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	20	18	20	19	20	19
Units: Titer
geometric mean (confidence interval 95%)	2896.3 (1738.8 to 4824.3)	1290.2 (675.2 to 2465.3)	2610.3 (1265.9 to 5382.4)	2949.6 (1550.2 to 5612.3)	2610.3 (1506.5 to 4522.8)	1474.8 (815.0 to 2668.9)

BNT162b2 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.52

Confidence interval

level

95%

sides

2-sided

lower limit

0.25

upper limit

1.09

BNT162b2 OMI 30 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

2.04

BNT162b2 30 + BNT162b2 OMI 30 vs BNT162b2 30

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.66

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

1.36

BNT162b2 15 + BNT162b2 OMI 15 vs BNT162b2 30

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 [15 mcg] + BNT162b2 OMI [15 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

1.59

BNT162b2 OMI 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

2.68

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers at Month 3

Top of page

End point title

SSF: GMT and GMR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers at Month 3 ^[57]

End point description

GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at 3 months were reported in this endpoint in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. GMR was reported in the statistical analysis section. All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 3

Notes
[57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	20	19	21	19	19	21
Units: Titer
geometric mean (confidence interval 95%)	222.9 (123.3 to 402.7)	132.8 (63.7 to 276.7)	322.5 (147.6 to 704.6)	458.9 (206.8 to 1018.6)	296.2 (143.2 to 612.6)	141.3 (86.4 to 231.1)

BNT162b2 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

1.76

BNT162b2 30 + BNT162b2 OMI 30 vs BNT162b2 30

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

2.04

BNT162b2 15 + BNT162b2 OMI 15 vs BNT162b2 30

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 [15 mcg] + BNT162b2 OMI [15 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

2.33

BNT162b2 OMI 30 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

3.85

BNT162b2 OMI 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

2.12

Confidence interval

level

95%

sides

2-sided

lower limit

0.92

upper limit

4.91

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers at Month 6

Top of page

End point title

SSF: GMT and GMR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers at Month 6 ^[58]

End point description

GMTs of SARS-CoV-2 Omicron BA.1 strain neutralizing titers at 6 months were reported in this endpoint in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. GMR was reported in the statistical analysis section. All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 6

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

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	19	21	20	20	20
Units: Titer
geometric mean (confidence interval 95%)	239.6 (98.8 to 581.4)	229.5 (68.7 to 766.4)	1058.4 (490.3 to 2284.6)	1722.2 (844.3 to 3512.9)	588.1 (280.3 to 1234.2)	284.0 (131.8 to 612.4)

BNT162b2 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.31

upper limit

3.12

BNT162b2 30 + BNT162b2 OMI 30 vs BNT162b2 30

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.28

Confidence interval

level

95%

sides

2-sided

lower limit

0.41

upper limit

4.03

BNT162b2 15 + BNT162b2 OMI 15 vs BNT162b2 30

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 [15 mcg] + BNT162b2 OMI [15 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

2.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

7.1

BNT162b2 OMI 30 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

4.57

Confidence interval

level

95%

sides

2-sided

lower limit

1.49

upper limit

14.07

BNT162b2 OMI 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

7.3

Confidence interval

level

95%

sides

2-sided

lower limit

2.34

upper limit

22.76

Primary: SSF: GMT and GMR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Month 6

Top of page

End point title

SSF: GMT and GMR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Month 6 ^[59]

End point description

GMTs of SARS-CoV-2 reference strain neutralizing titers at 6 months were reported in this endpoint in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. GMR was reported in the statistical analysis section. All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 6

Notes
[59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	19	21	20	20	20
Units: Titer
geometric mean (confidence interval 95%)	1424.5 (667.9 to 3037.9)	1371.0 (508.5 to 3696.4)	2756.4 (1328.0 to 5721.4)	3956.5 (2256.3 to 6937.8)	2702.4 (1457.6 to 5010.0)	1097.5 (555.3 to 2169.1)

BNT162b2 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

2.7

BNT162b2 OMI 30 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

5.2

BNT162b2 30 + BNT162b2 OMI 30 vs BNT162b2 30

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

2.24

BNT162b2 15 + BNT162b2 OMI 15 vs BNT162b2 30

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 [15 mcg] + BNT162b2 OMI [15 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

4.75

BNT162b2 OMI 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

2.99

Confidence interval

level

95%

sides

2-sided

lower limit

1.13

upper limit

7.94

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers at Month 6

Top of page

End point title

SSF: GMT and GMR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers at Month 6 ^[60]

End point description

GMTs of SARS-CoV-2 Omicron BA.4/BA.5 strain neutralizing titers at 6 months were reported in this endpoint in descriptive data section. GMTs and the 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on Student's t distribution). Assay results below the LLOQ were set to 0.5*LLOQ. GMR was reported in the statistical analysis section. All-available immunogenicity population included all randomised subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 6

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

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	19	21	20	20	20
Units: Titer
geometric mean (confidence interval 95%)	203.2 (85.5 to 483.1)	265.5 (75.9 to 928.9)	645.1 (281.1 to 1480.5)	1305.2 (601.1 to 2834.1)	430.5 (204.7 to 905.4)	187.4 (80.5 to 436.3)

BNT162b2 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.44

upper limit

5.12

BNT162b2 OMI 30 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

3.22

Confidence interval

level

95%

sides

2-sided

lower limit

0.99

upper limit

10.46

BNT162b2 30 + BNT162b2 OMI 30 vs BNT162b2 30

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.28

upper limit

3.17

BNT162b2 15 + BNT162b2 OMI 15 vs BNT162b2 30

Statistical analysis description

GMRs and 2-sided 95% CIs were calculated by exponentiating the difference in LS means (BNT162b2 [15 mcg] + BNT162b2 OMI [15 mcg] - BNT162b2 [30 mcg]) and the corresponding CIs based on analysis of logarithmically transformed assay results using a linear regression model with terms of baseline assay results (log scale) and vaccine group.

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

2.08

Confidence interval

level

95%

sides

2-sided

lower limit

0.63

upper limit

6.89

BNT162b2 OMI 60 mcg vs BNT162b2 30 mcg

Statistical analysis description

Comparison groups

SSF: BNT162b2 30 mcg v SSF: BNT162b2 OMI 60 mcg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other

Method

Parameter type

Geometric mean ratio (GMR)

Point estimate

6.46

Confidence interval

level

95%

sides

2-sided

lower limit

1.96

upper limit

21.27

Primary: SSF: Geometric Mean Fold-Rise (GMFR) of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers From Before the Study Vaccination to Day 7 After Vaccination

Top of page

End point title

SSF: Geometric Mean Fold-Rise (GMFR) of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers From Before the Study Vaccination to Day 7 After Vaccination ^[61] ^[62]

End point description

GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to Day 7 was reported in this endpoint. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution). All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From before the study vaccination to Day 7 after vaccination

Notes
[61] - 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
[62] - 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: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	21	20	20	20
Units: Fold rise
geometric mean (confidence interval 95%)	3.5 (2.1 to 5.8)	2.9 (1.6 to 5.4)	6.8 (4.3 to 10.7)	8.6 (5.1 to 14.3)	4.3 (2.0 to 9.1)	9.8 (6.9 to 14.0)

No statistical analyses for this end point

Primary: SSF: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Before the Study Vaccination to Day 7 After Vaccination

Top of page

End point title

SSF: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Before the Study Vaccination to Day 7 After Vaccination ^[63] ^[64]

End point description

GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to Day 7 was reported in this endpoint. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution). All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From before the study vaccination to Day 7 after vaccination

Notes
[63] - 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
[64] - 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: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	21	20	20	20
Units: Fold rise
geometric mean (confidence interval 95%)	3.5 (2.5 to 5.0)	3.1 (1.8 to 5.2)	3.4 (2.2 to 5.1)	4.8 (3.0 to 7.5)	3.4 (1.4 to 8.1)	6.3 (3.9 to 10.2)

No statistical analyses for this end point

Primary: SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers From Before the Study Vaccination to Day 7 After Vaccination

Top of page

End point title

SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers From Before the Study Vaccination to Day 7 After Vaccination ^[65] ^[66]

End point description

GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to Day 7 was reported in this endpoint. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution). All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From before the study vaccination to Day 7 after vaccination

Notes
[65] - 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
[66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	16	21	20	20	21
Units: Fold rise
geometric mean (confidence interval 95%)	2.8 (2.1 to 3.7)	2.8 (1.8 to 4.4)	3.6 (2.5 to 5.2)	3.2 (2.2 to 4.8)	2.9 (1.9 to 4.4)	4.7 (3.4 to 6.5)

No statistical analyses for this end point

Primary: SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination

Top of page

End point title

SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination ^[67] ^[68]

End point description

GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to 1 month was reported in this endpoint. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution). All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From before the study vaccination to 1 month after vaccination

Notes
[67] - 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
[68] - 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: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	20	20	20	20
Units: Fold rise
geometric mean (confidence interval 95%)	10.1 (5.5 to 18.4)	5.4 (2.6 to 11.4)	20.4 (11.8 to 35.3)	18.4 (9.5 to 35.6)	13.0 (6.7 to 25.1)	21.1 (11.5 to 38.8)

No statistical analyses for this end point

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

Top of page

End point title

SSF: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination ^[69] ^[70]

End point description

GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 1 month was reported in this endpoint. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution). All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From before the study vaccination to 1 month after vaccination

Notes
[69] - 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
[70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	20	20	20	20
Units: Fold rise
geometric mean (confidence interval 95%)	8.6 (5.5 to 13.6)	5.0 (2.5 to 10.0)	7.2 (4.7 to 10.9)	11.3 (6.2 to 20.8)	6.7 (3.7 to 12.1)	8.6 (4.1 to 17.8)

No statistical analyses for this end point

Primary: SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination

Top of page

End point title

SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers From Before the Study Vaccination to 1 Month After Vaccination ^[71] ^[72]

End point description

GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to 1 month was reported in this endpoint. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution). All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From before the study vaccination to 1 month after vaccination

Notes
[71] - 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
[72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	20	18	21	20	20	20
Units: Fold rise
geometric mean (confidence interval 95%)	5.9 (3.8 to 9.1)	4.7 (3.1 to 7.1)	7.5 (4.6 to 12.3)	9.8 (7.3 to 13.3)	6.7 (3.5 to 13.0)	9.5 (6.0 to 15.2)

No statistical analyses for this end point

Primary: SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination

Top of page

End point title

SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination ^[73] ^[74]

End point description

GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to 3 months was reported in this endpoint. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution). All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From before the study vaccination to 3 months after vaccination

Notes
[73] - 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
[74] - 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: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	20	18	20	19	20	19
Units: Fold rise
geometric mean (confidence interval 95%)	5.9 (2.7 to 12.8)	3.3 (1.4 to 7.5)	13.5 (6.0 to 30.0)	17.9 (8.7 to 36.5)	6.5 (3.2 to 13.1)	12.0 (6.4 to 22.3)

No statistical analyses for this end point

Primary: SSF: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination

Top of page

End point title

SSF: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination ^[75] ^[76]

End point description

GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 3 months was reported in this endpoint. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution). All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From before the study vaccination to 3 months after vaccination

Notes
[75] - 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
[76] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	20	18	20	19	20	19
Units: Fold rise
geometric mean (confidence interval 95%)	5.0 (2.9 to 8.5)	3.2 (1.6 to 6.3)	5.6 (2.6 to 11.9)	8.6 (4.3 to 17.2)	3.2 (1.8 to 5.8)	4.5 (2.4 to 8.2)

No statistical analyses for this end point

Primary: SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination

Top of page

End point title

SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers From Before the Study Vaccination to 3 Months After Vaccination ^[77] ^[78]

End point description

GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to 3 months was reported in this endpoint. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution). All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From before the study vaccination to 3 months after vaccination

Notes
[77] - 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
[78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	20	18	21	19	19	21
Units: Fold rise
geometric mean (confidence interval 95%)	8.6 (4.3 to 16.9)	7.4 (3.7 to 14.9)	16.0 (7.5 to 34.0)	18.5 (9.2 to 37.3)	7.2 (4.1 to 12.7)	9.4 (5.9 to 15.2)

No statistical analyses for this end point

Primary: SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination

Top of page

End point title

SSF: GMFR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination ^[79] ^[80]

End point description

GMFR of SARS-CoV-2 Omicron BA.1 strain-neutralizing titers before vaccination to 6 months was reported in this endpoint. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution). All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From before the study vaccination to 6 months after vaccination

Notes
[79] - 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
[80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	19	21	20	20	20
Units: Fold rise
geometric mean (confidence interval 95%)	5.8 (2.2 to 15.0)	6.9 (1.6 to 30.4)	33.1 (13.7 to 79.6)	46.9 (17.6 to 124.7)	7.5 (2.4 to 22.8)	12.6 (5.8 to 27.3)

No statistical analyses for this end point

Primary: SSF: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination

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End point title

SSF: GMFR of SARS-CoV-2 Reference-Strain–Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination ^[81] ^[82]

End point description

GMFR of SARS-CoV-2 reference-strain-neutralizing titers before vaccination to 6 months was reported in this endpoint. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution). All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From before the study vaccination to 6 months after vaccination

Notes
[81] - 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
[82] - 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: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	19	21	20	20	20
Units: Fold rise
geometric mean (confidence interval 95%)	2.6 (1.1 to 6.1)	3.6 (1.0 to 12.7)	6.3 (2.6 to 15.2)	12.6 (6.0 to 26.1)	3.4 (1.3 to 8.9)	3.9 (1.8 to 8.2)

No statistical analyses for this end point

Primary: SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination

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End point title

SSF: GMFR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers From Before the Study Vaccination to 6 Months After Vaccination ^[83] ^[84]

End point description

GMFR of SARS-CoV-2 Omicron BA.4/BA.5 strain-neutralizing titers before vaccination to 6 months was reported in this endpoint. GMFR and the corresponding 2-sided CIs were calculated by exponentiating the mean logarithm of the fold rises from before vaccination and the corresponding CIs (based on the student's t distribution). All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

From before the study vaccination to 6 months after vaccination

Notes
[83] - 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
[84] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	21	20	20	20
Units: Fold rise
geometric mean (confidence interval 95%)	7.5 (2.8 to 20.2)	16.6 (4.1 to 66.8)	32.0 (12.7 to 80.7)	55.7 (22.2 to 140.0)	10.2 (3.7 to 28.0)	13.0 (5.4 to 31.4)

No statistical analyses for this end point

Primary: SSF: Percentages of Subjects With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Day 7

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End point title

SSF: Percentages of Subjects With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Day 7 ^[85] ^[86]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of subjects achieving seroresponse on Day 7 was reported in this endpoint. All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Day 7

Notes
[85] - 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
[86] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	21	20	20	20
Units: Percentage of subjects
number (confidence interval 95%)	52.4 (29.8 to 74.3)	44.4 (21.5 to 69.2)	71.4 (47.8 to 88.7)	85.0 (62.1 to 96.8)	55.0 (31.5 to 76.9)	90.0 (68.3 to 98.8)

No statistical analyses for this end point

Primary: SSF: Percentages of Subjects With Seroresponse to the Reference-Strain-Neutralizing Titers at Day 7

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End point title

SSF: Percentages of Subjects With Seroresponse to the Reference-Strain-Neutralizing Titers at Day 7 ^[87] ^[88]

End point description

End point type

Primary

End point timeframe

Day 7

Notes
[87] - 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
[88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	21	20	20	20
Units: Percentage of subjects
number (confidence interval 95%)	52.4 (29.8 to 74.3)	55.6 (30.8 to 78.5)	61.9 (38.4 to 81.9)	80.0 (56.3 to 94.3)	55.0 (31.5 to 76.9)	80.0 (56.3 to 94.3)

No statistical analyses for this end point

Primary: SSF: Percentages of Subjects With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Day 7

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End point title

SSF: Percentages of Subjects With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Day 7 ^[89] ^[90]

End point description

End point type

Primary

End point timeframe

Day 7

Notes
[89] - 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
[90] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	16	21	20	20	21
Units: Percentage of subjects
number (confidence interval 95%)	33.3 (14.6 to 57.0)	43.8 (19.8 to 70.1)	42.9 (21.8 to 66.0)	40.0 (19.1 to 63.9)	40.0 (19.1 to 63.9)	61.9 (38.4 to 81.9)

No statistical analyses for this end point

Primary: SSF: Percentages of Subjects With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 1

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End point title

SSF: Percentages of Subjects With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 1 ^[91] ^[92]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of subjects achieving seroresponse at 1 month was reported in this endpoint. All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 1

Notes
[91] - 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
[92] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	20	20	20	20
Units: Percentage of subjects
number (confidence interval 95%)	85.7 (63.7 to 97.0)	61.1 (35.7 to 82.7)	90.0 (68.3 to 98.8)	85.0 (62.1 to 96.8)	90.0 (68.3 to 98.8)	85.0 (62.1 to 96.8)

No statistical analyses for this end point

Primary: SSF: Percentages of Subjects With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 1

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End point title

SSF: Percentages of Subjects With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 1 ^[93] ^[94]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of subjects achieving seroresponse at 1 month was reported in this endpoint. All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 1

Notes
[93] - 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
[94] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	20	20	20	20
Units: Percentage of subjects
number (confidence interval 95%)	81.0 (58.1 to 94.6)	61.1 (35.7 to 82.7)	85.0 (62.1 to 96.8)	85.0 (62.1 to 96.8)	70.0 (45.7 to 88.1)	75.0 (50.9 to 91.3)

No statistical analyses for this end point

Primary: SSF: Percentages of Subjects With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 1

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End point title

SSF: Percentages of Subjects With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 1 ^[95] ^[96]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of subjects achieving seroresponse at 1 month was reported in this endpoint. All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 1

Notes
[95] - 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
[96] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	20	18	21	20	20	20
Units: Percentage of subjects
number (confidence interval 95%)	75.0 (50.9 to 91.3)	61.1 (35.7 to 82.7)	66.7 (43.0 to 85.4)	95.0 (75.1 to 99.9)	80.0 (56.3 to 94.3)	85.0 (62.1 to 96.8)

No statistical analyses for this end point

Primary: SSF: Percentages of Subjects With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 3

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End point title

SSF: Percentages of Subjects With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 3 ^[97] ^[98]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of subjects achieving seroresponse at 3 months was reported in this endpoint. All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 3

Notes
[97] - 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
[98] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	20	18	20	19	20	19
Units: Percentage of subjects
number (confidence interval 95%)	65.0 (40.8 to 84.6)	50.0 (26.0 to 74.0)	75.0 (50.9 to 91.3)	84.2 (60.4 to 96.6)	70.0 (45.7 to 88.1)	89.5 (66.9 to 98.7)

No statistical analyses for this end point

Primary: SSF: Percentages of Subjects With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 3

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End point title

SSF: Percentages of Subjects With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 3 ^[99] ^[100]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of subjects achieving seroresponse at 3 months was reported in this endpoint. All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 3

Notes
[99] - 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
[100] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	20	18	20	19	20	19
Units: Percentage of subjects
number (confidence interval 95%)	65.0 (40.8 to 84.6)	55.6 (30.8 to 78.5)	65.0 (40.8 to 84.6)	78.9 (54.4 to 93.9)	55.0 (31.5 to 76.9)	63.2 (38.4 to 83.7)

No statistical analyses for this end point

Primary: SSF: Percentages of Subjects With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 3

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End point title

SSF: Percentages of Subjects With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 3 ^[101] ^[102]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of subjects achieving seroresponse at 3 months was reported in this endpoint. All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 3

Notes
[101] - 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
[102] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	20	18	21	19	19	21
Units: Percentage of subjects
number (confidence interval 95%)	75.0 (50.9 to 91.3)	61.1 (35.7 to 82.7)	85.7 (63.7 to 97.0)	84.2 (60.4 to 96.6)	63.2 (38.4 to 83.7)	85.7 (63.7 to 97.0)

No statistical analyses for this end point

Primary: SSF: Percentages of Subjects With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 6

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End point title

SSF: Percentages of Subjects With Seroresponse to Omicron BA.1 Strain-Neutralizing Titers at Month 6 ^[103] ^[104]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of subjects achieving seroresponse at 6 months was reported in this endpoint. All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 6

Notes
[103] - 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
[104] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	19	21	20	20	20
Units: Percentage of subjects
number (confidence interval 95%)	42.9 (21.8 to 66.0)	47.4 (24.4 to 71.1)	85.7 (63.7 to 97.0)	90.0 (68.3 to 98.8)	65.0 (40.8 to 84.6)	85.0 (62.1 to 96.8)

No statistical analyses for this end point

Primary: SSF: Percentages of Subjects With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 6

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End point title

SSF: Percentages of Subjects With Seroresponse to the Reference-Strain-Neutralizing Titers at Month 6 ^[105] ^[106]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of subjects achieving seroresponse at 6 months was reported in this endpoint. All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 6

Notes
[105] - 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
[106] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	19	21	20	20	20
Units: Percentage of subjects
number (confidence interval 95%)	42.9 (21.8 to 66.0)	42.1 (20.3 to 66.5)	61.9 (38.4 to 81.9)	85.0 (62.1 to 96.8)	55.0 (31.5 to 76.9)	50.0 (27.2 to 72.8)

No statistical analyses for this end point

Primary: SSF: Percentages of Subjects With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 6

Top of page

End point title

SSF: Percentages of Subjects With Seroresponse to Omicron BA.4/BA.5 Strain-Neutralizing Titers at Month 6 ^[107] ^[108]

End point description

Seroresponse was defined as achieving >= 4-fold rise from baseline (before the study vaccination). If the baseline measurement is below the lower limit of quantification (LLOQ), the postvaccination measure of >= 4 × LLOQ is considered a seroresponse. Exact 2-sided CI, based on the Clopper and Pearson method was used. Percentage of subjects achieving seroresponse at 6 months was reported in this endpoint. All-available immunogenicity population included all randomised or assigned subjects who received the study intervention with a valid and determinate immunogenicity result after vaccination. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

Month 6

Notes
[107] - 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
[108] - 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: No statistical analysis was planned for this endpoint

End point values	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Number of subjects analysed	21	18	21	20	20	20
Units: Percentage of subjects
number (confidence interval 95%)	52.4 (29.8 to 74.3)	50.0 (26.0 to 74.0)	85.7 (63.7 to 97.0)	90.0 (68.3 to 98.8)	70.0 (45.7 to 88.1)	75.0 (50.9 to 91.3)

No statistical analyses for this end point

Secondary: SSA: Occurrence of First Severe COVID-19 Infection (FDA Definition) per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection: Evaluable Efficacy Population

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End point title

SSA: Occurrence of First Severe COVID-19 Infection (FDA Definition) per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection: Evaluable Efficacy Population ^[109]

End point description

Occurrence of first severe COVID-19 infection based on FDA definition after booster dose without past SARS-CoV-2 infection is reported. FDA definition: confirmed COVID-19 and presence of at least 1 of the following: 1) clinical signs at rest indicative of severe systemic illness (respiratory rate greater than or equal to [≥]30 breaths per minute, heart rate ≥125 beats per minute, oxygen saturation less than or equal to [≤]93% on room air at sea level, or Horovitz quotient <300 mmHg); 2) respiratory failure (needing high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation); 3) evidence of shock (systolic blood pressure [BP] <90 mmHg, diastolic BP <60 mmHg, or requiring vasopressors); 4) significant acute renal, hepatic, or neurologic dysfunction; 5) admission to an intensive care unit; 6) death. Evaluable efficacy population assessed. HIV positive subjects were excluded from this analysis. Here, 'N'=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

From 7 Days after booster vaccination (Surveillance time [1000 person-year]: BNT162b2- 1.105, Placebo- 0.951)

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

End point values	SSA: BNT162b2 30 mcg: Blinded and Open Label Period	SSA: Placebo: Blinded Period
Number of subjects analysed	4639	4601
Units: Number of cases
number (not applicable)	0	2

BNT162b2 30 mcg versus Placebo

Comparison groups

SSA: BNT162b2 30 mcg: Blinded and Open Label Period v SSA: Placebo: Blinded Period

Number of subjects included in analysis

9240

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Surveillance Time

Point estimate

100

Confidence interval

level

95%

sides

2-sided

lower limit

-358.6

upper limit

100

Secondary: SSA: Occurrence of First Severe COVID-19 Infection (FDA Definition) per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection: Evaluable Efficacy Population

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End point title

SSA: Occurrence of First Severe COVID-19 Infection (FDA Definition) per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection: Evaluable Efficacy Population ^[110]

End point description

Occurrence of first severe COVID-19 infection based on FDA definition after booster dose with and without past SARS-CoV-2 infection is reported. FDA definition: confirmed COVID-19 and presence of at least 1 of the following: 1) clinical signs at rest indicative of severe systemic illness (respiratory rate ≥30 breaths per minute, heart rate ≥125 beats per minute, oxygen saturation ≤93% on room air at sea level, or Horovitz quotient <300 mm Hg); 2) respiratory failure (defined as needing high-flow oxygen, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation); 3) evidence of shock (systolic BP <90 mm Hg, diastolic BP <60 mm Hg, or requiring vasopressors); 4) significant acute renal, hepatic, or neurologic dysfunction; 5) admission to an intensive care unit; 6) death. Evaluable efficacy population assessed. HIV positive subjects were excluded from this analysis. Here, 'N'=subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

From 7 Days after booster vaccination (Surveillance time [1000 person-year]: BNT162b2- 1.182, Placebo- 1.011)

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

End point values	SSA: BNT162b2 30 mcg: Blinded and Open Label Period	SSA: Placebo: Blinded Period
Number of subjects analysed	4911	4861
Units: Number of cases
number (not applicable)	0	2

BNT162b2 30 mcg versus Placebo

Statistical analysis description

2-Sided CI for RVE is derived based on the Clopper and Pearson method adjusted for surveillance time.

Comparison groups

SSA: BNT162b2 30 mcg: Blinded and Open Label Period v SSA: Placebo: Blinded Period

Number of subjects included in analysis

9772

Analysis specification

Pre-specified

Analysis type

superiority

Method

Parameter type

Adjusted Surveillance Time

Point estimate

100

Confidence interval

level

95%

sides

2-sided

lower limit

-355.5

upper limit

100

Secondary: SSA: Occurrence of First Severe COVID-19 Infection (CDC Definition) per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection

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End point title

SSA: Occurrence of First Severe COVID-19 Infection (CDC Definition) per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection ^[111]

End point description

Occurrence of first severe COVID-19 infection based on CDC definition after booster dose with and without past SARS-CoV-2 infection is reported. CDC definition: confirmed COVID-19 AND presence of at least 1 of the following: 1) hospitalization; 2) admission to an intensive care unit; 3) intubation or mechanical ventilation; 4) death. Evaluable efficacy population included eligible randomized subjects who received the booster vaccination as randomised and had no other important protocol deviations as determined by the clinician. HIV positive subjects were excluded from this analysis. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

From 7 Days after booster vaccination

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

End point values	SSA: BNT162b2 30 mcg: Blinded and Open Label Period	SSA: Placebo: Blinded Period
Number of subjects analysed	4977	4942
Units: Number of cases
number (not applicable)	0	0

No statistical analyses for this end point

Secondary: SSA: Occurrence of First Severe COVID-19 Infection (CDC Definition) per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection

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End point title

SSA: Occurrence of First Severe COVID-19 Infection (CDC Definition) per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection ^[112]

End point description

Occurrence of first severe COVID-19 infection based on CDC definition after booster dose without past SARS-CoV-2 infection is reported. CDC definition: confirmed COVID-19 and presence of at least 1 of the following: 1) hospitalization; 2) admission to an intensive care unit; 3) intubation or mechanical ventilation; 4) death. Evaluable efficacy population included eligible randomized subjects who received the booster vaccination as randomised and had no other important protocol deviations as determined by the clinician. HIV positive subjects were excluded from this analysis. Here, 'Number of Subjects Analysed' signifies subjects evaluable for this endpoint.

End point type

Secondary

End point timeframe

From 7 Days after booster vaccination

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

End point values	SSA: BNT162b2 30 mcg: Blinded and Open Label Period	SSA: Placebo: Blinded Period
Number of subjects analysed	4689	4664
Units: Number of cases
number (not applicable)	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Death/SAEs: 6 months after last dose (or 1 month after each dose for SSB, or 6 months after BNT162b2 for SSA original placebo). Non-SAEs: 1 month after each booster dose (or after BNT162b2 for SSA original placebo)

Adverse event reporting additional description

Same event may appear as both AE and SAE but are distinct events. An event may be categorised as serious in 1 subject and non-serious in another, or a subject may have experienced both AE and non-SAE. For SSB and SSF, MedDRA version used is v25.1.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

v25.0

Reporting group title

SSA: BNT162b2 30 mcg- Blinded and Open Label Period

Reporting group description

Subjects received one dose (30 microgram) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSA: Placebo: Blinded Period

Reporting group description

Subjects received placebo (normal saline solution of 0.9 percent [%] sodium chloride) intramuscularly.

Reporting group title

SSA: Original Placebo/BNT162b2 (30 mcg)- Open Label Period

Reporting group description

Reporting group title

SSB: BNT162b2

Reporting group description

Subjects received one dose (30 microgram) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSB: Placebo

Reporting group description

Subjects received placebo (normal saline solution of 0.9 percent [%] sodium chloride) intramuscularly.

Reporting group title

SSF: BNT162b2 30 mcg

Reporting group description

Subjects received one dose (30 mcg) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 60 mcg

Reporting group description

Subjects received one dose (60 mcg) of BNT162b2 intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 OMI 30 mcg

Reporting group description

Subjects received one dose (30 mcg) of BNT162b2 Omicron (OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 OMI 60 mcg

Reporting group description

Subjects received one dose (60 mcg) of BNT162b2 Omicron (OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg

Reporting group description

Subjects received a total of 30 mcg BNT162b2 (15 mcg BNT162b2 and 15 mcg BNT162b2 OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Reporting group title

SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg

Reporting group description

Subjects received a total of 60 mcg BNT162b2 (30 mcg BNT162b2 and 30 mcg BNT162b2 OMI) intramuscularly in the deltoid muscle of the non-dominant arm.

Serious adverse events	SSA: BNT162b2 30 mcg- Blinded and Open Label Period	SSA: Placebo: Blinded Period	SSA: Original Placebo/BNT162b2 (30 mcg)- Open Label Period	SSB: BNT162b2	SSB: Placebo	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Total subjects affected by serious adverse events
subjects affected / exposed	73 / 5080 (1.44%)	42 / 5041 (0.83%)	45 / 4429 (1.02%)	2 / 1453 (0.14%)	2 / 1463 (0.14%)	0 / 21 (0.00%)	1 / 19 (5.26%)	1 / 21 (4.76%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)
number of deaths (all causes)	5	2	5	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Brain neoplasm
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Biliary neoplasm
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Adrenocortical carcinoma
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Adenocarcinoma of colon
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Hepatic adenoma
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Follicular lymphoma
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Breast cancer
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Hepatic cancer metastatic
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Breast cancer stage II
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Malignant melanoma in situ
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Nervous system neoplasm
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Lung carcinoma cell type unspecified stage II
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Invasive ductal breast carcinoma
subjects affected / exposed	2 / 5080 (0.04%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	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
Pancreatic carcinoma metastatic
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Pancreatic carcinoma
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Ovarian cancer
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Pituitary tumour benign
subjects affected / exposed	1 / 5080 (0.02%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Breast cancer stage I
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Renal cell carcinoma
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Squamous cell carcinoma of the vagina
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Uterine cancer
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Prostate cancer
subjects affected / exposed	3 / 5080 (0.06%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 3	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
Colorectal adenoma
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Rhabdomyosarcomas
alternative dictionary used: MedDRA v25.1
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	1 / 1463 (0.07%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	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
Vascular disorders
Hypertension
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Shock haemorrhagic
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Deep vein thrombosis
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Penetrating aortic ulcer
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Pregnancy, puerperium and perinatal conditions
Abortion incomplete
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Abortion spontaneous
subjects affected / exposed	2 / 5080 (0.04%)	1 / 5041 (0.02%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	1 / 1463 (0.07%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1	0 / 0	0 / 1	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
Abortion complete
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
General disorders and administration site conditions
Chest pain
subjects affected / exposed	1 / 5080 (0.02%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	1 / 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
Death
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	1 / 5080 (0.02%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Sudden cardiac death
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Food allergy
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Reproductive system and breast disorders
Adenomyosis
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	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 failure
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Pulmonary embolism
subjects affected / exposed	0 / 5080 (0.00%)	3 / 5041 (0.06%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	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 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Dyspnoea
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Psychiatric disorders
Suicidal ideation
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Completed suicide
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Hepatic enzyme increased
subjects affected / exposed	2 / 5080 (0.04%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	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
Injury, poisoning and procedural complications
Acetabulum fracture
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Clavicle fracture
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Arterial injury
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Craniocerebral injury
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Femur fracture
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Hip fracture
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Humerus fracture
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Joint dislocation
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	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
Ligament rupture
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Pelvic fracture
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Road traffic accident
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Stoma complication
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Subdural haematoma
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Thoracic vertebral fracture
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Ankle fracture
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Multiple injuries
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Concussion
alternative dictionary used: MedDRA v25.1
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	1 / 1453 (0.07%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	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
Congenital, familial and genetic disorders
Hypertrophic cardiomyopathy
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	3 / 5080 (0.06%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 3	1 / 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
Atrial fibrillation
subjects affected / exposed	3 / 5080 (0.06%)	0 / 5041 (0.00%)	2 / 4429 (0.05%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 2	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
Coronary artery disease
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Cardiac failure
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Myocardial infarction
subjects affected / exposed	2 / 5080 (0.04%)	1 / 5041 (0.02%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myopericarditis
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Coronary artery insufficiency
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Pericarditis
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Tachycardia
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	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
Ventricular extrasystoles
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Nervous system disorders
Cerebral venous thrombosis
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Cerebrovascular accident
subjects affected / exposed	2 / 5080 (0.04%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 2	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
Cerebral haemorrhage
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Toxic encephalopathy
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Syncope
subjects affected / exposed	3 / 5080 (0.06%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	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
Seizure
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Intracranial aneurysm
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Toxic leukoencephalopathy
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Headache
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Migraine
alternative dictionary used: MedDRA v25.1
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	1 / 1453 (0.07%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	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
Blood and lymphatic system disorders
Sickle cell anaemia with crisis
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Ear and labyrinth disorders
Vertigo
alternative dictionary used: MedDRA v25.1
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Gastrointestinal disorders
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Gastric fistula
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Colitis
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Pancreatitis acute
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Lower gastrointestinal haemorrhage
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Intestinal perforation
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Hiatus hernia
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Small intestinal obstruction
subjects affected / exposed	1 / 5080 (0.02%)	1 / 5041 (0.02%)	2 / 4429 (0.05%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 2	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
Pancreatic pseudocyst
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Hepatobiliary disorders
Bile duct stone
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Skin and subcutaneous tissue disorders
Vitiligo
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Renal and urinary disorders
Nephrolithiasis
subjects affected / exposed	3 / 5080 (0.06%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	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
End stage renal disease
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Acute kidney injury
subjects affected / exposed	0 / 5080 (0.00%)	2 / 5041 (0.04%)	2 / 4429 (0.05%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2	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 infarct
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Renal cyst
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Endocrine disorders
Goitre
subjects affected / exposed	1 / 5080 (0.02%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 5080 (0.02%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Arthralgia
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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 / 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
Intervertebral disc protrusion
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Intervertebral disc space narrowing
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Osteoarthritis
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	4 / 4429 (0.09%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 4	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
Osteonecrosis
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Neck pain
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Spondylolisthesis
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Spinal osteoarthritis
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Spinal stenosis
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Infections and infestations
Abdominal abscess
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Appendicitis
subjects affected / exposed	3 / 5080 (0.06%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 3	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
Abdominal sepsis
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Acquired immunodeficiency syndrome
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Appendicitis perforated
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Arthritis bacterial
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Cellulitis
alternative dictionary used: MedDRA v25.1
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	1 / 1453 (0.07%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1	0 / 1	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
COVID-19 pneumonia
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
COVID-19
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Cholangitis infective
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Complicated appendicitis
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Device related infection
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Diverticulitis
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	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
Gastroenteritis
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	2 / 4429 (0.05%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	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
Infected skin ulcer
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Infection
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Liver abscess
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Lyme disease
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Osteomyelitis
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Peritonitis
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Pelvic abscess
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Pneumocystis jirovecii pneumonia
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Salmonellosis
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Sepsis
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Septic shock
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Staphylococcal skin infection
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Urinary tract infection
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	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
Empyema
subjects affected / exposed	0 / 5080 (0.00%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Bronchitis
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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
Metabolism and nutrition disorders
Hypervolaemia
subjects affected / exposed	1 / 5080 (0.02%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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
Obesity
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	1 / 4429 (0.02%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (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

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

Non-serious adverse events	SSA: BNT162b2 30 mcg- Blinded and Open Label Period	SSA: Placebo: Blinded Period	SSA: Original Placebo/BNT162b2 (30 mcg)- Open Label Period	SSB: BNT162b2	SSB: Placebo	SSF: BNT162b2 30 mcg	SSF: BNT162b2 60 mcg	SSF: BNT162b2 OMI 30 mcg	SSF: BNT162b2 OMI 60 mcg	SSF: BNT162b2 15 mcg + BNT162b2 OMI 15 mcg	SSF: BNT162b2 30 mcg + BNT162b2 OMI 30 mcg
Total subjects affected by non serious adverse events
subjects affected / exposed	1201 / 5080 (23.64%)	202 / 5041 (4.01%)	771 / 4429 (17.41%)	1180 / 1453 (81.21%)	615 / 1463 (42.04%)	17 / 21 (80.95%)	19 / 19 (100.00%)	20 / 21 (95.24%)	18 / 20 (90.00%)	18 / 20 (90.00%)	20 / 21 (95.24%)
Investigations
SARS-CoV-2 test positive
alternative dictionary used: MedDRA v25.1
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	18 / 1453 (1.24%)	26 / 1463 (1.78%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	18	26	0	0	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	267 / 5080 (5.26%)	54 / 5041 (1.07%)	144 / 4429 (3.25%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	269	54	144	0	0	0	0	1	0	0	0
Syncope
alternative dictionary used: MedDRA v25.1
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	1 / 19 (5.26%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Headache (HEADACHE)
alternative dictionary used: MedDRA v25.1
alternative assessment type: Systematic
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	585 / 1453 (40.26%)	332 / 1463 (22.69%)	6 / 21 (28.57%)	5 / 19 (26.32%)	5 / 21 (23.81%)	11 / 20 (55.00%)	7 / 20 (35.00%)	8 / 21 (38.10%)
occurrences all number	0	0	0	585	332	6	5	5	11	7	8
General disorders and administration site conditions
Injection site pain
subjects affected / exposed	673 / 5080 (13.25%)	83 / 5041 (1.65%)	412 / 4429 (9.30%)	17 / 1453 (1.17%)	3 / 1463 (0.21%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	675	83	412	17	3	0	0	0	0	0	0
Pain
subjects affected / exposed	139 / 5080 (2.74%)	16 / 5041 (0.32%)	122 / 4429 (2.75%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	140	16	122	0	0	0	0	0	0	0	0
Chills
subjects affected / exposed	243 / 5080 (4.78%)	11 / 5041 (0.22%)	107 / 4429 (2.42%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	243	11	107	0	0	0	0	0	0	0	0
Fatigue
subjects affected / exposed	383 / 5080 (7.54%)	66 / 5041 (1.31%)	228 / 4429 (5.15%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	383	66	228	0	0	0	0	0	0	0	0
Pyrexia
subjects affected / exposed	258 / 5080 (5.08%)	8 / 5041 (0.16%)	142 / 4429 (3.21%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	258	8	143	0	0	0	0	0	0	0	0
Injection site erythema (REDNESS)
alternative dictionary used: MedDRA v25.1
alternative assessment type: Systematic
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	74 / 1453 (5.09%)	9 / 1463 (0.62%)	4 / 21 (19.05%)	4 / 19 (21.05%)	5 / 21 (23.81%)	4 / 20 (20.00%)	2 / 20 (10.00%)	6 / 21 (28.57%)
occurrences all number	0	0	0	74	9	4	4	5	4	2	6
Fatigue (FATIGUE)
alternative dictionary used: MedDRA v25.1
alternative assessment type: Systematic
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	723 / 1453 (49.76%)	356 / 1463 (24.33%)	10 / 21 (47.62%)	7 / 19 (36.84%)	9 / 21 (42.86%)	11 / 20 (55.00%)	10 / 20 (50.00%)	12 / 21 (57.14%)
occurrences all number	0	0	0	723	356	10	7	9	11	10	12
Chills (CHILLS)
alternative dictionary used: MedDRA v25.1
alternative assessment type: Systematic
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	278 / 1453 (19.13%)	69 / 1463 (4.72%)	3 / 21 (14.29%)	3 / 19 (15.79%)	5 / 21 (23.81%)	5 / 20 (25.00%)	1 / 20 (5.00%)	3 / 21 (14.29%)
occurrences all number	0	0	0	278	69	3	3	5	5	1	3
Injection site pain (PAIN)
alternative dictionary used: MedDRA v25.1
alternative assessment type: Systematic
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	1038 / 1453 (71.44%)	163 / 1463 (11.14%)	15 / 21 (71.43%)	18 / 19 (94.74%)	19 / 21 (90.48%)	16 / 20 (80.00%)	15 / 20 (75.00%)	19 / 21 (90.48%)
occurrences all number	0	0	0	1038	163	15	18	19	16	15	19
Injection site swelling (SWELLING)
alternative dictionary used: MedDRA v25.1
alternative assessment type: Systematic
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	86 / 1453 (5.92%)	7 / 1463 (0.48%)	3 / 21 (14.29%)	3 / 19 (15.79%)	3 / 21 (14.29%)	3 / 20 (15.00%)	3 / 20 (15.00%)	6 / 21 (28.57%)
occurrences all number	0	0	0	86	7	3	3	3	3	3	6
Pyrexia (FEVER)
alternative dictionary used: MedDRA v25.1
alternative assessment type: Systematic
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	74 / 1453 (5.09%)	17 / 1463 (1.16%)	2 / 21 (9.52%)	2 / 19 (10.53%)	2 / 21 (9.52%)	2 / 20 (10.00%)	1 / 20 (5.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	74	17	2	2	2	2	1	1
Blood and lymphatic system disorders
Lymphadenopathy
subjects affected / exposed	141 / 5080 (2.78%)	3 / 5041 (0.06%)	59 / 4429 (1.33%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	147	3	59	0	0	0	0	0	0	0	0
Eye disorders
Eye pruritis
alternative dictionary used: MedDRA v25.1
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Gastrointestinal disorders
Nausea
subjects affected / exposed	54 / 5080 (1.06%)	16 / 5041 (0.32%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	54	16	0	0	0	0	0	0	1	0	0
Diarrhoea (DIARRHEA)
alternative dictionary used: MedDRA v25.1
alternative assessment type: Systematic
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	109 / 1453 (7.50%)	77 / 1463 (5.26%)	3 / 21 (14.29%)	1 / 19 (5.26%)	2 / 21 (9.52%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	109	77	3	1	2	1	0	0
Vomiting (VOMITING)
alternative dictionary used: MedDRA v25.1
alternative assessment type: Systematic
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	37 / 1453 (2.55%)	13 / 1463 (0.89%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	37	13	0	0	0	0	0	0
Abdominal pain
alternative dictionary used: MedDRA v25.1
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	248 / 5080 (4.88%)	21 / 5041 (0.42%)	118 / 4429 (2.66%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	248	21	119	0	0	0	0	0	0	0	0
Pain in extremity
subjects affected / exposed	58 / 5080 (1.14%)	1 / 5041 (0.02%)	0 / 4429 (0.00%)	0 / 1453 (0.00%)	0 / 1463 (0.00%)	0 / 21 (0.00%)	0 / 19 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 21 (0.00%)
occurrences all number	58	1	0	0	0	0	0	1	0	0	0
Arthralgia (JOINT PAIN)
alternative dictionary used: MedDRA v25.1
alternative assessment type: Systematic
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	178 / 1453 (12.25%)	55 / 1463 (3.76%)	3 / 21 (14.29%)	3 / 19 (15.79%)	3 / 21 (14.29%)	4 / 20 (20.00%)	2 / 20 (10.00%)	2 / 21 (9.52%)
occurrences all number	0	0	0	178	55	3	3	3	4	2	2
Myalgia (MUSCLE PAIN)
alternative dictionary used: MedDRA v25.1
alternative assessment type: Systematic
subjects affected / exposed	0 / 5080 (0.00%)	0 / 5041 (0.00%)	0 / 4429 (0.00%)	402 / 1453 (27.67%)	88 / 1463 (6.02%)	4 / 21 (19.05%)	8 / 19 (42.11%)	5 / 21 (23.81%)	6 / 20 (30.00%)	5 / 20 (25.00%)	6 / 21 (28.57%)
occurrences all number	0	0	0	402	88	4	8	5	6	5	6

More information

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Were there any global substantial amendments to the protocol? Yes

28 Oct 2021

Addition of Substudy B

20 Jan 2022

Addition of Substudy F. Confirmation of the safety reporting time periods for Substudy F.

08 Feb 2022

Updated text to clarify that subjects may be enrolled if they completed a 2-dose primary series of BNT162b2 (30 mcg doses) at least 5 months prior to randomisation for all subjects.

03 May 2022

Added text to allow inclusion of subjects who have received a booster (third) dose of BNT162b2 at least 4 months prior to randomisation. Timing of prior BNT162b2 for subjects with 2 prior doses updated to 4 months prior to randomisation.

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 3 Master Protocol to Evaluate Additional Dose(s) Of BNT162b2 In Healthy Individuals Previously Vaccinated With BNT162b2

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population

Primary: SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population

Primary: SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population

Primary: SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Interim Analysis: Evaluable Efficacy Population

Primary: SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population

Primary: SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population

Primary: SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population

Primary: SSA: Occurrence of First COVID-19 Infection After Booster Dose per 1000 Person-Years of Blinded Follow-up With and Without Evidence of Past SARS-CoV-2 Infection at Final Analysis: Evaluable Efficacy Population

Primary: SSA: Percentage of Subjects Reporting Adverse Events

Primary: SSA: Percentage of Subjects Reporting Adverse Events

Primary: SSA: Percentage of Subjects Reporting Serious Adverse Events

Primary: SSA: Percentage of Subjects Reporting Serious Adverse Events

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level pre-Dose; Vaccination 1

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level pre-Dose; Vaccination 1

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level Within 5 Days After Vaccination 1

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level Within 5 Days After Vaccination 1

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level pre-Vaccination 2 (1 Month After Vaccination 1)

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level pre-Vaccination 2 (1 Month After Vaccination 1)

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level 1 Month After Vaccination 2

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level 1 Month After Vaccination 2

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level Within 5 Days After Vaccination 2

Primary: SSB: Percentage of Subjects With Elevated Troponin I Level Within 5 Days After Vaccination 2

Primary: SSB: Percentage of Subjects With Local Reactions Within 7 Days After Vaccination 1

Primary: SSB: Percentage of Subjects With Local Reactions Within 7 Days After Vaccination 1

Primary: SSB: Percentage of Subjects With Local Reactions Within 7 Days After Vaccination 2

Primary: SSB: Percentage of Subjects With Local Reactions Within 7 Days After Vaccination 2

Primary: SSB: Percentage of Subjects With Systemic Events Within 7 Days After Vaccination 1

Primary: SSB: Percentage of Subjects With Systemic Events Within 7 Days After Vaccination 1

Primary: SSB: Percentage of Subjects With Systemic Events Within 7 Days After Vaccination 2

Primary: SSB: Percentage of Subjects With Systemic Events Within 7 Days After Vaccination 2

Primary: SSB: Percentage of Subjects Reporting Adverse Events (AEs) 1 Month After Vaccination 1

Primary: SSB: Percentage of Subjects Reporting Adverse Events (AEs) 1 Month After Vaccination 1

Primary: SSB: Percentage of Subjects Reporting Adverse Events (AEs) 1 Month After Vaccination 2

Primary: SSB: Percentage of Subjects Reporting Adverse Events (AEs) 1 Month After Vaccination 2

Primary: SSB: Percentage of Subjects Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 1

Primary: SSB: Percentage of Subjects Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 1

Primary: SSB: Percentage of Subjects Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 2

Primary: SSB: Percentage of Subjects Reporting Serious Adverse Events (SAEs) 1 Month After Vaccination 2

Primary: SSF: Percentage of Subjects With Local Reactions Within 7 Days After Study Vaccination

Primary: SSF: Percentage of Subjects With Local Reactions Within 7 Days After Study Vaccination

Primary: SSF: Percentage of Subjects With Systemic Events Within 7 Days After Study Vaccination

Primary: SSF: Percentage of Subjects With Systemic Events Within 7 Days After Study Vaccination

Primary: SSF: Percentage of Subjects Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination

Primary: SSF: Percentage of Subjects Reporting Adverse Events (AEs) Within 1 Month After Study Vaccination

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

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

Primary: SSF: Geometric Mean Titer (GMTs) of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers Before Vaccination

Primary: SSF: Geometric Mean Titer (GMTs) of SARS-CoV-2 Omicron BA.1 Strain Neutralizing Titers Before Vaccination

Primary: SSF: GMTs of SARS-CoV-2 Reference-Strain–Neutralizing Titers Before Vaccination

Primary: SSF: GMTs of SARS-CoV-2 Reference-Strain–Neutralizing Titers Before Vaccination

Primary: SSF: GMTs of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers Before Vaccination

Primary: SSF: GMTs of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers Before Vaccination

Primary: SSF: GMT and Geometric Mean Ratios (GMR) of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers at Day 7

Primary: SSF: GMT and Geometric Mean Ratios (GMR) of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers at Day 7

Primary: SSF: GMT and GMR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Day 7

Primary: SSF: GMT and GMR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Day 7

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers at Day 7

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.4/BA.5 Strain Neutralizing Titers at Day 7

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers at Month 1

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers at Month 1

Primary: SSF: GMT and GMR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Month 1

Primary: SSF: GMT and GMR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Month 1

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers at Month 1

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers at Month 1

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers at Month 3

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.1 Strain–Neutralizing Titers at Month 3

Primary: SSF: GMT and GMR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Month 3

Primary: SSF: GMT and GMR of SARS-CoV-2 Reference-Strain–Neutralizing Titers at Month 3

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers at Month 3

Primary: SSF: GMT and GMR of SARS-CoV-2 Omicron BA.4/BA.5 Strain–Neutralizing Titers at Month 3

Clinical Trial Results:
A Phase 3 Master Protocol to Evaluate Additional Dose(s) Of BNT162b2 In Healthy Individuals Previously Vaccinated With BNT162b2