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Clinical Trial Results:
A Phase 3 Open-Label Clinical Trial to Study the Immunogenicity and Safety of 9-Valent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine (V503) in Chinese females 9 to 45 Years of Age

Summary
EudraCT number	2024-000582-24
Trial protocol	Outside EU/EEA
Global end of trial date	22 Jul 2025

Results information
Results version number	v1(current)
This version publication date	01 Feb 2026
First version publication date	01 Feb 2026
Other versions

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

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Trial information

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Sponsor protocol code

V503-024

ISRCTN number

US NCT number

NCT03903562

WHO universal trial number (UTN)

Sponsor organisation name

Merck Sharp & Dohme LLC

Sponsor organisation address

126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@msd.com

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

Final

Date of interim/final analysis

22 Jul 2025

Is this the analysis of the primary completion data?

Yes

Primary completion date

28 Feb 2025

Global end of trial reached?

Yes

Global end of trial date

22 Jul 2025

Was the trial ended prematurely?

Main objective of the trial

This study will investigate the immunogenicity and safety of the 9vHPV vaccine in healthy Chinese females 9 to 45 years of age. The study consists of Stage I (Day 1 to Month 7) and Stage II (post Month 7 to Month 60). Stage II will report the long-term immunogenicity and safety in 9 to 19 years of age group only. Dual-primary hypotheses of Stage I: 9vHPV vaccine induces non-inferior immune responses in females 9 to 19 years of age who are seronegative at Day 1 to the relevant HPV type compared to females 20 to 26 years of age who are seronegative at Day 1 to relevant HPV type, as measured by anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 geometric mean titers at 1 month post Dose 3; 9vHPV vaccine induces non-inferior immune responses in females 27 to 45 years of age who are seronegative Day 1 to relevant HPV type compared to females 20 to 26 years of age who are seronegative Day 1 to relevant HPV type, measured by seroconversion percentages to each of HPV types at 1 month post Dose 3.

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.

Background therapy

Evidence for comparator

Actual start date of recruitment

27 Apr 2019

Long term follow-up planned

Yes

Long term follow-up rationale

Regulatory reason, Scientific research

Long term follow-up duration

53 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

China: 1990

Worldwide total number of subjects

1990

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)

166

Adolescents (12-17 years)

425

Adults (18-64 years)

1399

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Healthy Chinese females received 9-Valent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine (V503). The study consists of two stages. Stage I is from Day 1 through 1 month post last dose (Month 7). Participants in the 9 to 19 years of age group who completed 3 doses of V503 were eligible for Stage II and followed up to Month 60.

Screening details

1990 participants were enrolled, and 1988 received at least one dose of study vaccination.

Period 1 title

Stage I

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

9 to 19 Years of Age

Arm description

Chinese females 9 to 19 years of age received a 0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Arm type

Experimental

Investigational medicinal product name

9-valent human papillomavirus (HPV) (types 6, 11, 16, 18, 31, 33, 45, 52, and 58) L1 VLP vaccine

Investigational medicinal product code

Other name

V503 GARDASIL 9

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

20 to 26 Years of Age

Arm description

Chinese females 20 to 26 years of age received a 0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Arm type

Experimental

Investigational medicinal product name

9vHPV (types 6, 11, 16, 18, 31, 33, 45, 52, and 58) L1 VLP vaccine

Investigational medicinal product code

Other name

V503 GARDASIL 9

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

27 to 45 Years of Age

Arm description

Chinese females 27 to 45 years of received a 0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Arm type

Experimental

Investigational medicinal product name

9vHPV (types 6, 11, 16, 18, 31, 33, 45, 52, and 58) L1 VLP vaccine

Investigational medicinal product code

Other name

V503 GARDASIL 9

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Number of subjects in period 1	9 to 19 Years of Age	20 to 26 Years of Age	27 to 45 Years of Age
Started	690	650	650
Vaccination 1	688	650	650
Vaccination 2	683	647	644
Vaccination 3	682	635	641
Completed	682	635	641
Not completed	8	15	9
Consent withdrawn by subject	5	15	9
withdrawal by parent/guardian	3	-	-

Period 2 title

Stage II

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

9 to 19 Years of Age

Arm description

Participants in the 9 to 19 years of age group who completed 3 doses of V503 were eligible for Stage II and followed up to Month 60.

Arm type

Experimental

Investigational medicinal product name

9vHPV (types 6, 11, 16, 18, 31, 33, 45, 52, and 58) L1 VLP vaccine

Investigational medicinal product code

Other name

V503 GARDASIL 9

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Number of subjects in period 2 ^[1]	9 to 19 Years of Age
Started	682
Completed	645
Not completed	37
Consent withdrawn by subject	25
Lost to follow-up	12

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: The number that started Stage II is the number that completed 3 vaccinations in Arm 1.

Baseline characteristics

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Reporting group title

9 to 19 Years of Age

Reporting group description

Chinese females 9 to 19 years of age received a 0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Reporting group title

20 to 26 Years of Age

Reporting group description

Chinese females 20 to 26 years of age received a 0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Reporting group title

27 to 45 Years of Age

Reporting group description

Chinese females 27 to 45 years of received a 0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Reporting group values	9 to 19 Years of Age	20 to 26 Years of Age	27 to 45 Years of Age	Total
Number of subjects	690	650	650	1990
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	166	0	0	166
Adolescents (12-17 years)	425	0	0	425
Adults (18-64 years)	99	650	650	1399
From 65-84 years	0	0	0	0
85 years and over	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	14.0 ( 3.0 )	23.1 ( 1.7 )	35.5 ( 5.1 )	-
Gender categorical
Units: Subjects
Female	690	650	650	1990
Male	0	0	0	0
Race
Units: Subjects
Asian	690	650	650	1990
Ethnicity
Units: Subjects
Not Hispanic or Latino	690	650	650	1990
Age
Units: Years
arithmetic mean (standard deviation)	14.0 ( 3.0 )	23.1 ( 1.7 )	35.5 ( 5.1 )	-

End points

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Reporting group title

9 to 19 Years of Age

Reporting group description

Chinese females 9 to 19 years of age received a 0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Reporting group title

20 to 26 Years of Age

Reporting group description

Chinese females 20 to 26 years of age received a 0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Reporting group title

27 to 45 Years of Age

Reporting group description

Chinese females 27 to 45 years of received a 0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Reporting group title

9 to 19 Years of Age

Reporting group description

Participants in the 9 to 19 years of age group who completed 3 doses of V503 were eligible for Stage II and followed up to Month 60.

Subject analysis set title

Stage I: 9 to 15 Years of Age

Subject analysis set type

Per protocol

Subject analysis set description

Chinese females 9 to 15 years of age, a subset of the 9 to 19 years of age group, received a 0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Primary: Stage I: Competitive Luminex Immunoassay (cLIA) Geometric Mean Titers (GMTs) for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age and 20 to 26 Years of Age: Month 7

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End point title

Stage I: Competitive Luminex Immunoassay (cLIA) Geometric Mean Titers (GMTs) for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age and 20 to 26 Years of Age: Month 7 ^[1]

End point description

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined using cLIA. The HPV-9 cLIA assay was used to quantify the antibodies. This assay evaluated the serological response before and after 9vHPV vaccination and measured HPV infection-induced antibodies. The GMT for each HPV type was expressed as milli Merck units/mL (mMU/mL). Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type and in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

1 month post vaccination 3 (Month 7)

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 analyses were planned for arm 3 (27 to 45 Years of Age) for this endpoint.

End point values	9 to 19 Years of Age	20 to 26 Years of Age
Number of subjects analysed	688	650
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6 (n=640, 567)	1129.7 (1069.8 to 1193.0)	861.7 (817.5 to 908.4)
Anti-HPV 11 (n=640, 567)	926.7 (876.4 to 979.8)	702.6 (662.7 to 744.9)
Anti-HPV 16 (n=662, 595)	4972.3 (4696.9 to 5263.9)	3723.7 (3513.0 to 3946.9)
Anti-HPV 18 (n=630, 574)	1438.4 (1349.0 to 1533.6)	1031.6 (964.4 to 1103.6)
Anti-HPV 31 (n=657, 587)	1161.5 (1093.2 to 1234.2)	821.9 (770.5 to 876.7)
Anti-HPV 33 (n=642, 589)	664.3 (626.3 to 704.7)	497.5 (468.1 to 528.8)
Anti-HPV 45 (n=655, 598)	442.9 (415.0 to 472.7)	299.1 (279.8 to 319.9)
Anti-HPV 52 (n=649, 572)	505.9 (478.4 to 535.0)	397.8 (374.4 to 422.8)
Anti-HPV 58 (n=645, 580)	725.3 (685.6 to 767.4)	535.9 (503.2 to 570.8)

Anti-HPV 6

Statistical analysis description

GMT Ratio

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.31

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.2

upper limit

1.43

Notes
[2] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 19 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 11

Statistical analysis description

GMT Ratio

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.32

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.2

upper limit

1.45

Notes
[3] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 19 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 16

Statistical analysis description

GMT Ratio

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.34

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.22

upper limit

1.47

Notes
[4] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 19 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 18

Statistical analysis description

GMT Ratio

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.39

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.25

upper limit

1.55

Notes
[5] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 19 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 31

Statistical analysis description

GMT Ratio

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.41

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.28

upper limit

1.56

Notes
[6] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 19 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 45

Statistical analysis description

GMT Ratio

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.48

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.33

upper limit

1.65

Notes
[7] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 19 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 33

Statistical analysis description

GMT Ratio

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.34

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.21

upper limit

1.47

Notes
[8] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 19 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 52

Statistical analysis description

GMT Ratio

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.27

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.16

upper limit

1.4

Notes
[9] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 19 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 58

Statistical analysis description

GMT Ratio

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.35

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.23

upper limit

1.49

Notes
[10] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 19 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Primary: Stage I: Percentage of Participants 27 to 45 Years of Age and 20 to 26 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

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End point title

Stage I: Percentage of Participants 27 to 45 Years of Age and 20 to 26 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7 ^[11]

End point description

The percentage of participants who are seropositive for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 was determined using cLIA. Seroconversion was defined as changing serostatus from seronegative at baseline (Day 1) to seropositive at 1 month after last dose. Cutoff values for HPV seropositivity are ≥50, 29, 41, 59, 29, 22, 15, 20, and 15 mMU/mL for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, respectively. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

1 month post vaccination 3 (Month 7)

Notes
[11] - 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 analyses were performed for arm 1 (9 to 19 Years of Age) for this endpoint.

End point values	20 to 26 Years of Age	27 to 45 Years of Age
Number of subjects analysed	650	650
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 ≥50 mMU/mL (n=567, 517)	100.0 (99.4 to 100.0)	100.0 (99.3 to 100.0)
Anti-HPV 11 ≥29 mMU/mL (n=567, 517)	100.0 (99.4 to 100.0)	100.0 (99.3 to 100.0)
Anti-HPV 16 ≥41 mMU/mL (n=595, 575)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 18 ≥59 mMU/mL (n=574, 575)	99.8 (99.0 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 31 ≥29 mMU/mL (n=587, 576)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 33 ≥22 mMU/mL (n=589, 569)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 45 ≥15 mMU/mL (n=598, 598)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 52 ≥20 mMU/mL (n=572, 578)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 58 ≥15 mMU/mL (n=580, 534)	100.0 (99.4 to 100.0)	100.0 (99.3 to 100.0)

Anti-HPV 6 ≥50 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (27 to 45 years of age) - (20 to 26 years of age)

Comparison groups

20 to 26 Years of Age v 27 to 45 Years of Age

Number of subjects included in analysis

1300

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[12]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-1

upper limit

0.9

Notes
[12] - Criterion for non-inferiority with respect to the difference (females 27 to 45 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 11 ≥29 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (27 to 45 years of age) - (20 to 26 years of age)

Comparison groups

20 to 26 Years of Age v 27 to 45 Years of Age

Number of subjects included in analysis

1300

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[13]

P-value

< 0.0001

Method

ANOVA

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-1

upper limit

0.9

Notes
[13] - Criterion for non-inferiority with respect to the difference (females 27 to 45 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 16 ≥41 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (27 to 45 years of age) - (20 to 26 years of age)

Comparison groups

20 to 26 Years of Age v 27 to 45 Years of Age

Number of subjects included in analysis

1300

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[14]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.9

upper limit

0.8

Notes
[14] - Criterion for non-inferiority with respect to the difference (females 27 to 45 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 18 ≥59 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (27 to 45 years of age) - (20 to 26 years of age)

Comparison groups

20 to 26 Years of Age v 27 to 45 Years of Age

Number of subjects included in analysis

1300

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[15]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

0.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.7

upper limit

1.2

Notes
[15] - Criterion for non-inferiority with respect to the difference (females 27 to 45 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 31 ≥29 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (27 to 45 years of age) - (20 to 26 years of age)

Comparison groups

20 to 26 Years of Age v 27 to 45 Years of Age

Number of subjects included in analysis

1300

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[16]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.9

upper limit

0.8

Notes
[16] - Criterion for non-inferiority with respect to the difference (females 27 to 45 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 45 ≥15 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (27 to 45 years of age) - (20 to 26 years of age)

Comparison groups

20 to 26 Years of Age v 27 to 45 Years of Age

Number of subjects included in analysis

1300

Analysis specification

Pre-specified

Analysis type

other ^[17]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.8

upper limit

0.8

Notes
[17] - Criterion for non-inferiority with respect to the difference (females 27 to 45 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 33 ≥22 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (27 to 45 years of age) - (20 to 26 years of age)

Comparison groups

20 to 26 Years of Age v 27 to 45 Years of Age

Number of subjects included in analysis

1300

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[18]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.9

upper limit

0.8

Notes
[18] - Criterion for non-inferiority with respect to the difference (females 27 to 45 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 52 ≥20 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (27 to 45 years of age) - (20 to 26 years of age)

Comparison groups

20 to 26 Years of Age v 27 to 45 Years of Age

Number of subjects included in analysis

1300

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.9

upper limit

0.9

Notes
[19] - Criterion for non-inferiority with respect to the difference (females 27 to 45 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 58 ≥15 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (27 to 45 years of age) - (20 to 26 years of age)

Comparison groups

20 to 26 Years of Age v 27 to 45 Years of Age

Number of subjects included in analysis

1300

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[20]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.9

upper limit

0.9

Notes
[20] - Criterion for non-inferiority with respect to the difference (females 27 to 45 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age: Month 12

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End point title

Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age: Month 12 ^[21]

End point description

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined using cLIA. The HPV-9 cLIA assay was used to quantify the antibodies. This assay evaluated the serological response before and after 9vHPV vaccination and measured HPV infection-induced antibodies. The GMT for each HPV type was expressed as mMU/mL. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type and in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

Month 12

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 between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6 (n=638)	420.3 (393.3 to 449.1)
Anti-HPV 11 (n=638)	341.9 (320.1 to 365.3)
Anti-HPV 16 (n=660)	1748.7 (1636.7 to 1868.3)
Anti-HPV 18 (n=628)	472.2 (440.6 to 506.1)
Anti-HPV 31 (n=655)	403.5 (375.6 to 433.5)
Anti-HPV 33 (n=640)	237.7 (221.8 to 254.8)
Anti-HPV 45 (n=653)	144.0 (133.4 to 155.3)
Anti-HPV 52 (n=647)	187.6 (175.8 to 200.2)
Anti-HPV 58 (n=643)	272.5 (255.5 to 290.7)

No statistical analyses for this end point

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 24

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End point title

Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 24 ^[22]

End point description

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined using cLIA. The HPV-9 cLIA assay was used to quantify the antibodies. This assay evaluated the serological response before and after 9vHPV vaccination and measured HPV infection-induced antibodies. The GMT for each HPV type was expressed as mMU/mL. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type and in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

Month 24

Notes
[22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6 (n=636)	210.2 (196.4 to 225.0)
Anti-HPV 11 (n=636)	172.2 (160.7 to 184.5)
Anti-HPV 16 (n=658)	774.8 (717.2 to 837.1)
Anti-HPV 18 (n=627)	226.9 (211.8 to 243.0)
Anti-HPV 31 (n=653)	205.3 (190.4 to 221.4)
Anti-HPV 33 (n=638)	120.4 (112.2 to 129.2)
Anti-HPV 45 (n=651)	72.1 (66.8 to 77.8)
Anti-HPV 52 (n=645)	97.5 (91.3 to 104.2)
Anti-HPV 58 (n=641)	125.8 (117.0 to 135.3)

No statistical analyses for this end point

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 36

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End point title

Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 36 ^[23]

End point description

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined using cLIA. The HPV-9 cLIA assay was used to quantify the antibodies. This assay evaluated the serological response before and after 9vHPV vaccination and measured HPV infection-induced antibodies. The GMT for each HPV type was expressed as mMU/mL. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type and in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

Month 36

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 between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6 (n=616)	172.6 (161.6 to 184.4)
Anti-HPV 11 (n=616)	136.5 (127.6 to 146.0)
Anti-HPV 16 (n=637)	600.5 (554.3 to 650.6)
Anti-HPV 18 (n=609)	178.0 (166.3 to 190.5)
Anti-HPV 31 (n=633)	166.9 (154.7 to 180.0)
Anti-HPV 33 (n=618)	95.1 (88.6 to 102.1)
Anti-HPV 45 (n=631)	56.9 (52.8 to 61.4)
Anti-HPV 52 (n=626)	78.1 (73.2 to 83.4)
Anti-HPV 58 (n=620)	100.9 (93.9 to 108.5)

No statistical analyses for this end point

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 48

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End point title

Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 48 ^[24]

End point description

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined using cLIA. The HPV-9 cLIA assay was used to quantify the antibodies. This assay evaluated the serological response before and after 9vHPV vaccination and measured HPV infection-induced antibodies. The GMT for each HPV type was expressed as mMU/mL. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type and in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

Month 48

Notes
[24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6 (n=616)	170.3 (158.9 to 182.6)
Anti-HPV 11 (n=616)	123.4 (115.0 to 132.3)
Anti-HPV 16 (n=636)	612.6 (568.8 to 659.8)
Anti-HPV 18 (n=607)	151.9 (140.1 to 164.8)
Anti-HPV 31 (n=632)	165.6 (153.2 to 178.9)
Anti-HPV 33 (n=617)	87.9 (81.4 to 94.9)
Anti-HPV 45 (n=630)	53.5 (49.4 to 57.9)
Anti-HPV 52 (n=625)	75.3 (70.5 to 80.4)
Anti-HPV 58 (n=619)	97.1 (90.5 to 104.2)

No statistical analyses for this end point

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 60

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End point title

Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 60 ^[25]

End point description

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined using cLIA. The HPV-9 cLIA assay was used to quantify the antibodies. This assay evaluated the serological response before and after 9vHPV vaccination and measured HPV infection-induced antibodies. The GMT for each HPV type was expressed as mMU/mL. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type and in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

Month 60

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 between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6 (n=604)	154.2 (143.5 to 165.6)
Anti-HPV 11 (n=604)	111.3 (103.5 to 119.6)
Anti-HPV 16 (n=624)	541.7 (502.0 to 584.5)
Anti-HPV 18 (n=597)	132.9 (122.5 to 144.1)
Anti-HPV 31 (n=620)	147.1 (135.9 to 159.2)
Anti-HPV 33 (n=605)	79.0 (73.1 to 85.3)
Anti-HPV 45 (n=619)	48.3 (44.5 to 52.4)
Anti-HPV 52 (n=613)	68.6 (64.1 to 73.3)
Anti-HPV 58 (n=608)	86.8 (80.6 to 93.4)

No statistical analyses for this end point

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 12

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End point title

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 12 ^[26]

End point description

End point type

Primary

End point timeframe

Month 12

Notes
[26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 ≥50 mMU/mL (n=638)	99.5 (98.6 to 99.9)
Anti-HPV 11 ≥29 mMU/mL (n=638)	100.0 (99.4 to 100.0)
Anti-HPV 16 ≥41 mMU/mL (n=660)	100.0 (99.4 to 100.0)
Anti-HPV 18 ≥59 mMU/mL (n=628)	99.0 (97.9 to 99.6)
Anti-HPV 31 ≥29 mMU/mL (n=655)	99.4 (98.4 to 99.8)
Anti-HPV 33 ≥22 mMU/mL (n=640)	99.5 (98.6 to 99.9)
Anti-HPV 45 ≥15 mMU/mL (n=653)	98.9 (97.8 to 99.6)
Anti-HPV 52 ≥20 mMU/mL (n=647)	99.7 (98.9 to 100.0)
Anti-HPV 58 ≥15 mMU/mL (n=643)	100.0 (99.4 to 100.0)

No statistical analyses for this end point

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 24

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End point title

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 24 ^[27]

End point description

End point type

Primary

End point timeframe

Month 24

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 between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 ≥50 mMU/mL (n=636)	96.4 (94.6 to 97.7)
Anti-HPV 11 ≥29 mMU/mL (n=636)	98.3 (96.9 to 99.1)
Anti-HPV 16 ≥41 mMU/mL (n=658)	99.1 (98.0 to 99.7)
Anti-HPV 18 ≥59 mMU/mL (n=627)	95.7 (93.8 to 97.1)
Anti-HPV 31 ≥29 mMU/mL (n=653)	98.0 (96.6 to 98.9)
Anti-HPV 33 ≥22 mMU/mL (n=638)	98.0 (96.5 to 98.9)
Anti-HPV 45 ≥15 mMU/mL (n=651)	96.8 (95.1 to 98.0)
Anti-HPV 52 ≥20 mMU/mL (n=645)	96.9 (95.3 to 98.1)
Anti-HPV 58 ≥15 mMU/mL (n=641)	98.0 (96.6 to 98.9)

No statistical analyses for this end point

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 36

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End point title

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 36 ^[28]

End point description

The percentage of participants who are seropositive for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 was determined using cLIA. Seroconversion was defined as changing serostatus from seronegative at baseline (Day 1) to seropositive at 1 month after last dose. Cutoff values for HPV seropositivity are ≥65, 37, 79, 85, 46, 26, 21, 30 and 31 mMU/mL for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, respectively. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

Month 36

Notes
[28] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 ≥65 mMU/mL (n=616)	87.3 (84.5 to 89.9)
Anti-HPV 11 ≥37 mMU/mL (n=616)	94.5 (92.4 to 96.1)
Anti-HPV 16 ≥79 mMU/mL (n=637)	97.0 (95.4 to 98.2)
Anti-HPV 18 ≥85 mMU/mL (n=609)	80.5 (77.1 to 83.5)
Anti-HPV 31 ≥46 mMU/mL (n=633)	90.5 (88.0 to 92.7)
Anti-HPV 33 ≥26 mMU/mL (n=618)	94.8 (92.8 to 96.4)
Anti-HPV 45 ≥21 mMU/mL (n=631)	84.9 (81.9 to 87.6)
Anti-HPV 52 ≥30 mMU/mL (n=626)	86.9 (84.0 to 89.4)
Anti-HPV 58 ≥31 mMU/mL (n=620)	90.2 (87.5 to 92.4)

No statistical analyses for this end point

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 48

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End point title

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 48 ^[29]

End point description

The percentage of participants who are seropositive for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 was determined using cLIA. Seroconversion was defined as changing serostatus from seronegative at baseline (Day 1) to seropositive at 1 month after last dose. Cutoff values for HPV seropositivity are ≥34, 25, 32, 26, 15, 10, 10, 14 and 10 mMU/mL for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, respectively. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

Month 48

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 between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 ≥34 mMU/mL (n=616)	94.2 (92.0 to 95.9)
Anti-HPV 11 ≥25 mMU/mL (n=616)	95.9 (94.1 to 97.4)
Anti-HPV 16 ≥32 mMU/mL (n=636)	99.1 (98.0 to 99.7)
Anti-HPV 18 ≥26 mMU/mL (n=607)	92.3 (89.8 to 94.3)
Anti-HPV 31 ≥15 mMU/mL (n=632)	98.3 (96.9 to 99.1)
Anti-HPV 33 ≥10 mMU/mL (n=617)	97.4 (95.8 to 98.5)
Anti-HPV 45 ≥10 mMU/mL (n=630)	92.7 (90.4 to 94.6)
Anti-HPV 52 ≥14 mMU/mL (n=625)	96.8 (95.1 to 98.0)
Anti-HPV 58 ≥10 mMU/mL (n=619)	98.5 (97.3 to 99.3)

No statistical analyses for this end point

Primary: Stage II: Percentage of Participants 9 to 19 years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 60

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End point title

Stage II: Percentage of Participants 9 to 19 years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 60 ^[30]

End point description

The percentage of participants who are seropositive for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 was determined using cLIA. Seroconversion was defined as changing serostatus from seronegative at baseline (Day 1) to seropositive at 1 month after last dose. Cutoff values for HPV seropositivity are ≥34, 25, 32, 26, 15, 10, 10, 14 and 10 mMU/mL for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, respectively. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

Month 60

Notes
[30] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 ≥34 mMU/mL (n=604)	92.5 (90.2 to 94.5)
Anti-HPV 11 ≥25 mMU/mL (n=604)	93.5 (91.3 to 95.4)
Anti-HPV 16 ≥32 mMU/mL (n=624)	98.9 (97.7 to 99.5)
Anti-HPV 18 ≥26 mMU/mL (n=597)	90.3 (87.6 to 92.5)
Anti-HPV 31 ≥15 mMU/mL (n=620)	97.6 (96.0 to 98.6)
Anti-HPV 33 ≥10 mMU/mL (n=605)	96.2 (94.4 to 97.6)
Anti-HPV 45 ≥10 mMU/mL (n=619)	89.7 (87.0 to 91.9)
Anti-HPV 52 ≥14 mMU/mL (n=613)	95.3 (93.3 to 96.8)
Anti-HPV 58 ≥10 mMU/mL (n=608)	97.9 (96.4 to 98.9)

No statistical analyses for this end point

Primary: Stage II: Immunoglobulin G Luminex Immunoassay (IgG LIA) GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 12

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End point title

Stage II: Immunoglobulin G Luminex Immunoassay (IgG LIA) GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 12 ^[31]

End point description

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined using IgG LIA. The HPV-9 IgG LIA assay was used to quantify the antibodies. This assay evaluated serological response before and after 9vHPV vaccination and measured HPV infection-induced antibodies. The GMT for each HPV type was expressed as mMU/mL. Although the same name (mMU/mL) is used for the unit of measurement of cLIA and IgG LIA, the ‘cLIA mMU/mL’ and the ‘IgG LIA mMU/mL’ are different units of measurement and cannot be directly compared. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type and in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no protocol violations that could interfere with evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

Month 12

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 between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6 (n=638)	355.1 (329.4 to 382.7)
Anti-HPV 11 (n=638)	290.5 (270.1 to 312.4)
Anti-HPV 16 (n=660)	1505.2 (1405.6 to 1611.9)
Anti-HPV 18 (n=628)	340.1 (314.5 to 367.8)
Anti-HPV 31 (n=655)	331.7 (307.2 to 358.2)
Anti-HPV 33 (n=640)	194.7 (180.6 to 210.0)
Anti-HPV 45 (n=653)	112.1 (103.3 to 121.7)
Anti-HPV 52 (n=647)	153.3 (142.7 to 164.8)
Anti-HPV 58 (n=643)	230.0 (214.6 to 246.4)

No statistical analyses for this end point

Primary: Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 24

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End point title

Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 24 ^[32]

End point description

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined using IgG LIA. The HPV-9 IgG LIA assay was used to quantify the antibodies. This assay evaluated the serological response before and after 9vHPV vaccination and measured HPV infection-induced antibodies. The GMT for each HPV type was expressed as mMU/mL. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type and in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

Month 24

Notes
[32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6 (n=636)	186.3 (172.2 to 201.5)
Anti-HPV 11 (n=636)	159.0 (147.3 to 171.7)
Anti-HPV 16 (n=658)	750.8 (695.2 to 810.8)
Anti-HPV 18 (n=627)	153.6 (140.4 to 168.0)
Anti-HPV 31 (n=653)	174.8 (161.1 to 189.6)
Anti-HPV 33 (n=638)	99.1 (91.3 to 107.5)
Anti-HPV 45 (n=651)	58.4 (53.5 to 63.9)
Anti-HPV 52 (n=645)	82.6 (76.7 to 89.1)
Anti-HPV 58 (n=641)	115.2 (106.8 to 124.4)

No statistical analyses for this end point

Primary: Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 36

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End point title

Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 36 ^[33]

End point description

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined using IgG LIA. The HPV-9 IgG LIA assay was used to quantify the antibodies. This assay evaluated the serological response before and after 9vHPV vaccination and measured HPV infection-induced antibodies. The GMT for each HPV type was expressed as mMU/mL. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type and in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

Month 36

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 between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6 (n=616)	143.2 (132.0 to 155.5)
Anti-HPV 11 (n=616)	121.9 (112.5 to 132.2)
Anti-HPV 16 (n=637)	566.1 (521.8 to 614.2)
Anti-HPV 18 (n=609)	112.3 (102.1 to 123.4)
Anti-HPV 31 (n=633)	137.3 (126.1 to 149.5)
Anti-HPV 33 (n=618)	75.4 (69.2 to 82.1)
Anti-HPV 45 (n=631)	44.2 (40.3 to 48.4)
Anti-HPV 52 (n=626)	65.0 (60.2 to 70.3)
Anti-HPV 58 (n=620)	90.0 (83.1 to 97.6)

No statistical analyses for this end point

Primary: Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 48

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End point title

Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 48 ^[34]

End point description

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined using IgG LIA. The HPV-9 IgG LIA assay was used to quantify the antibodies. This assay evaluated the serological response before and after 9vHPV vaccination and measured HPV infection-induced antibodies. The GMT for each HPV type was expressed as mMU/mL. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type and in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

Month 48

Notes
[34] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6 (n=616)	121.4 (111.9 to 131.8)
Anti-HPV 11 (n=616)	104.4 (96.3 to 113.2)
Anti-HPV 16 (n=636)	491.4 (452.7 to 533.4)
Anti-HPV 18 (n=607)	96.0 (87.2 to 105.7)
Anti-HPV 31 (n=632)	122.0 (112.0 to 133.0)
Anti-HPV 33 (n=617)	65.8 (60.4 to 71.8)
Anti-HPV 45 (n=630)	38.7 (35.4 to 42.4)
Anti-HPV 52 (n=625)	56.6 (52.3 to 61.3)
Anti-HPV 58 (n=619)	79.7 (73.5 to 86.5)

No statistical analyses for this end point

Primary: Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 60

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End point title

Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 60 ^[35]

End point description

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined using IgG LIA. The HPV-9 IgG LIA assay was used to quantify the antibodies. This assay evaluated the serological response before and after 9vHPV vaccination and measured HPV infection-induced antibodies. The GMT for each HPV type was expressed as mMU/mL. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type and in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

Month 60

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 between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6 (n=604)	106.8 (98.1 to 116.3)
Anti-HPV 11 (n=604)	91.3 (83.9 to 99.2)
Anti-HPV 16 (n=624)	433.6 (398.2 to 472.2)
Anti-HPV 18 (n=597)	81.9 (74.2 to 90.3)
Anti-HPV 31 (n=620)	106.1 (97.1 to 115.9)
Anti-HPV 33 (n=605)	58.3 (53.4 to 63.6)
Anti-HPV 45 (n=619)	33.6 (30.6 to 36.9)
Anti-HPV 52 (n=613)	49.6 (45.7 to 54.0)
Anti-HPV 58 (n=608)	70.8 (65.0 to 77.0)

No statistical analyses for this end point

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 12

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End point title

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 12 ^[36]

End point description

The percentage of participants who are seropositive for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 was determined using IgG LIA. Seroconversion was defined as changing serostatus from seronegative at baseline (Day 1) to seropositive at 1 month after last dose. Cutoff values for HPV seropositivity are ≥9, 6, 5, 5, 3, 4, 3, 5 and 5 mMU/mL for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, respectively. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Primary

End point timeframe

Month 12

Notes
[36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 ≥9 mMU/mL (n=638)	100.0 (99.4 to 100.0)
Anti-HPV 11 ≥6 mMU/mL (n=638)	100.0 (99.4 to 100.0)
Anti-HPV 16 ≥5 mMU/mL (n=660)	100.0 (99.4 to 100.0)
Anti-HPV 18 ≥5 mMU/mL (n=628)	100.0 (99.4 to 100.0)
Anti-HPV 31 ≥3 mMU/mL (n=655)	100.0 (99.4 to 100.0)
Anti-HPV 33 ≥4 mMU/mL (n=640)	100.0 (99.4 to 100.0)
Anti-HPV 45 ≥3 mMU/mL (n=653)	99.8 (99.1 to 100.0)
Anti-HPV 52 ≥5 mMU/mL (n=647)	99.8 (99.1 to 100.0)
Anti-HPV 58 ≥5 mMU/mL (n=643)	99.8 (99.1 to 100.0)

No statistical analyses for this end point

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 24

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End point title

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 24 ^[37]

End point description

End point type

Primary

End point timeframe

Month 24

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 between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 ≥9 mMU/mL (n=636)	99.8 (99.1 to 100.0)
Anti-HPV 11 ≥6 mMU/mL (n=636)	100.0 (99.4 to 100.0)
Anti-HPV 16 ≥5 mMU/mL (n=658)	100.0 (99.4 to 100.0)
Anti-HPV 18 ≥5 mMU/mL (n=627)	99.4 (98.4 to 99.8)
Anti-HPV 31 ≥3 mMU/mL (n=653)	99.8 (99.1 to 100.0)
Anti-HPV 33 ≥4 mMU/mL (n=638)	99.8 (99.1 to 100.0)
Anti-HPV 45 ≥3 mMU/mL (n=651)	99.1 (98.0 to 99.7)
Anti-HPV 52 ≥5 mMU/mL (n=645)	99.8 (99.1 to 100.0)
Anti-HPV 58 ≥5 mMU/mL (n=641)	99.5 (98.6 to 99.9)

No statistical analyses for this end point

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 36

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End point title

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 36 ^[38]

End point description

End point type

Primary

End point timeframe

Month 36

Notes
[38] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 ≥9 mMU/mL (n=616)	99.7 (98.8 to 100.0)
Anti-HPV 11 ≥6 mMU/mL (n=616)	99.7 (98.8 to 100.0)
Anti-HPV 16 ≥5 mMU/mL (n=637)	100.0 (99.4 to 100.0)
Anti-HPV 18 ≥5 mMU/mL (n=609)	98.7 (97.4 to 99.4)
Anti-HPV 31 ≥3 mMU/mL (n=633)	99.8 (99.1 to 100.0)
Anti-HPV 33 ≥4 mMU/mL (n=618)	99.4 (98.4 to 99.8)
Anti-HPV 45 ≥3 mMU/mL (n=631)	98.4 (97.1 to 99.2)
Anti-HPV 52 ≥5 mMU/mL (n=626)	99.2 (98.1 to 99.7)
Anti-HPV 58 ≥5 mMU/mL (n=620)	99.0 (97.9 to 99.6)

No statistical analyses for this end point

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 48

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End point title

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 48 ^[39]

End point description

End point type

Primary

End point timeframe

Month 48

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 between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 ≥9 mMU/mL (n=616)	99.2 (98.1 to 99.7)
Anti-HPV 11 ≥6 mMU/mL (n=616)	99.2 (98.1 to 99.7)
Anti-HPV 16 ≥5 mMU/mL (n=636)	100.0 (99.4 to 100.0)
Anti-HPV 18 ≥5 mMU/mL (n=607)	98.5 (97.2 to 99.3)
Anti-HPV 31 ≥3 mMU/mL (n=632)	99.5 (98.6 to 99.9)
Anti-HPV 33 ≥4 mMU/mL (n=617)	98.5 (97.2 to 99.3)
Anti-HPV 45 ≥3 mMU/mL (n=630)	98.6 (97.3 to 99.3)
Anti-HPV 52 ≥5 mMU/mL (n=625)	98.7 (97.5 to 99.4)
Anti-HPV 58 ≥5 mMU/mL (n=619)	99.0 (97.9 to 99.6)

No statistical analyses for this end point

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 60

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End point title

Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 60 ^[40]

End point description

End point type

Primary

End point timeframe

Month 60

Notes
[40] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No between-group statistical analyses were performed for this endpoint.

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 ≥9 mMU/mL (n=604)	99.0 (97.9 to 99.6)
Anti-HPV 11 ≥6 mMU/mL (n=604)	99.0 (97.9 to 99.6)
Anti-HPV 16 ≥5 mMU/mL (n=624)	100.0 (99.4 to 100.0)
Anti-HPV 18 ≥5 mMU/mL (n=597)	97.5 (95.9 to 98.6)
Anti-HPV 31 ≥3 mMU/mL (n=620)	99.7 (98.8 to 100.0)
Anti-HPV 33 ≥4 mMU/mL (n=605)	98.2 (96.8 to 99.1)
Anti-HPV 45 ≥3 mMU/mL (n=619)	97.9 (96.4 to 98.9)
Anti-HPV 52 ≥5 mMU/mL (n=613)	98.2 (96.8 to 99.1)
Anti-HPV 58 ≥5 mMU/mL (n=608)	98.7 (97.4 to 99.4)

No statistical analyses for this end point

Secondary: Stage I: Percentage of Participants 9 to 19 Years of Age and 20 to 26 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

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End point title

Stage I: Percentage of Participants 9 to 19 Years of Age and 20 to 26 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7 ^[41]

End point description

The percentage of participants who are seropositive for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 was determined using cLIA. Seroconversion was defined as changing serostatus from seronegative at baseline (Day 1) to seropositive at 1 month after last dose. Cutoff values for HPV seropositivity are ≥50, 29, 41, 59, 29, 22, 15, 20, and 15 mMU/mL for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, respectively. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Secondary

End point timeframe

1 month post vaccination 3 (Month 7)

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses were planned for arm 3 (27 to 45 Years of Age) for this endpoint.

End point values	9 to 19 Years of Age	20 to 26 Years of Age
Number of subjects analysed	688	650
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 ≥50 mMU/mL (n=640, 567)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 11 ≥29 mMU/mL (n=640, 567))	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 16 ≥41 mMU/mL (n=662, 595)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 18 ≥59 mMU/mL (n=630, 574)	100.0 (99.4 to 100.0)	99.8 (99.0 to 100.0)
Anti-HPV 31 ≥29 mMU/mL (n=657, 587)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 33 ≥22 mMU/mL (n=642, 589)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 45 ≥15 mMU/mL (n=655, 598)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 52 ≥20 mMU/mL (n=649. 572)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 58 ≥15 mMU/mL (n=645, 580)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)

Anti-HPV 18 ≥59 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (9 to 19 years of age) - (20 to 26 years of age)

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[42]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

0.2

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.6

upper limit

1.2

Notes
[42] - Criterion for non-inferiority with respect to the difference (females 9 to 19 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 16 ≥41 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (9 to 19 years of age) - (20 to 26 years of age)

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[43]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.8

upper limit

0.8

Notes
[43] - Criterion for non-inferiority with respect to the difference (females 9 to 19 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 11 ≥29 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (9 to 19 years of age) - (20 to 26 years of age)

Comparison groups

20 to 26 Years of Age v 9 to 19 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[44]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.8

upper limit

0.9

Notes
[44] - Criterion for non-inferiority with respect to the difference (females 9 to 19 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 6 ≥50 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (9 to 19 years of age) - (20 to 26 years of age)

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[45]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.8

upper limit

0.9

Notes
[45] - Criterion for non-inferiority with respect to the difference (females 9 to 19 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 52 ≥20 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (9 to 19 years of age) - (20 to 26 years of age)

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[46]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.8

upper limit

0.9

Notes
[46] - Criterion for non-inferiority with respect to the difference (females 9 to 19 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 45 ≥15 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (9 to 19 years of age) - (20 to 26 years of age)

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[47]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.8

upper limit

0.8

Notes
[47] - Criterion for non-inferiority with respect to the difference (females 9 to 19 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 33 ≥22 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (9 to 19 years of age) - (20 to 26 years of age)

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[48]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.8

upper limit

0.8

Notes
[48] - Criterion for non-inferiority with respect to the difference (females 9 to 19 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 58 ≥15 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (9 to 19 years of age) - (20 to 26 years of age)

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[49]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.8

upper limit

0.9

Notes
[49] - Criterion for non-inferiority with respect to the difference (females 9 to 19 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Anti-HPV 31 ≥29 mMU/mL

Statistical analysis description

Difference of Seroconversion Percentages (9 to 19 years of age) - (20 to 26 years of age)

Comparison groups

9 to 19 Years of Age v 20 to 26 Years of Age

Number of subjects included in analysis

1338

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[50]

P-value

< 0.0001

Method

Miettinen & Nurminen method

Parameter type

Difference of Seroconversion Percentages

Point estimate

Confidence interval

level

97.5%

sides

2-sided

lower limit

-0.8

upper limit

0.8

Notes
[50] - Criterion for non-inferiority with respect to the difference (females 9 to 19 years of age - females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than -5% for each HPV type.

Secondary: Stage I: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 15 Years of Age and 20 to 26 Years of Age: Month 7

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End point title

Stage I: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 15 Years of Age and 20 to 26 Years of Age: Month 7 ^[51]

End point description

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined using cLIA. The HPV-9 cLIA assay was used to quantify the antibodies. This assay evaluated the serological response before and after 9vHPV vaccination and measured HPV infection-induced antibodies. The GMT for each HPV type were expressed as mMU/mL. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type and in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Secondary

End point timeframe

1 month post vaccination 3 (Month 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 analyses were planned for arms 1 and 3 for this endpoint.

End point values	20 to 26 Years of Age	Stage I: 9 to 15 Years of Age
Number of subjects analysed	650	458
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6 (n=567, 426)	861.7 (817.5 to 908.4)	1201.1 (1123.6 to 1284.0)
Anti-HPV 11 (n=567, 426)	702.6 (662.7 to 744.9)	981.6 (917.5 to 1050.2)
Anti-HPV 16 (n=595, 441)	3723.7 (3513.0 to 3946.9)	5279.6 (4943.8 to 5638.3)
Anti-HPV 18 (n=574, 422)	1031.6 (964.4 to 1103.6)	1582.4 (1469.4 to 1704.1)
Anti-HPV 31 (n=587, 436)	821.9 (770.5 to 876.7)	1253.1 (1167.7 to 1344.9)
Anti-HPV 33 (n=589, 432)	497.5 (468.1 to 528.8)	699.6 (653.5 to 748.9)
Anti-HPV 45 (n=598, 437)	299.1 (279.8 to 319.9)	490.5 (454.3 to 529.6)
Anti-HPV 52 (n=572, 430)	397.8 (374.4 to 422.8)	535.1 (501.4 to 571.1)
Anti-HPV 58 (n=580, 429)	535.9 (503.2 to 570.8)	771.5 (721.8 to 824.6)

Anti-HPV 6

Statistical analysis description

GMT Ratio

Comparison groups

20 to 26 Years of Age v Stage I: 9 to 15 Years of Age

Number of subjects included in analysis

1108

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[52]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.39

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.27

upper limit

1.53

Notes
[52] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 15 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 11

Statistical analysis description

GMT Ratio

Comparison groups

20 to 26 Years of Age v Stage I: 9 to 15 Years of Age

Number of subjects included in analysis

1108

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[53]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.4

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.26

upper limit

1.55

Notes
[53] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 15 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 16

Statistical analysis description

GMT Ratio

Comparison groups

20 to 26 Years of Age v Stage I: 9 to 15 Years of Age

Number of subjects included in analysis

1108

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[54]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.42

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.28

upper limit

1.57

Notes
[54] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 15 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 18

Statistical analysis description

GMT Ratio

Comparison groups

20 to 26 Years of Age v Stage I: 9 to 15 Years of Age

Number of subjects included in analysis

1108

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[55]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.53

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.37

upper limit

1.72

Notes
[55] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 15 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 31

Statistical analysis description

GMT Ratio

Comparison groups

20 to 26 Years of Age v Stage I: 9 to 15 Years of Age

Number of subjects included in analysis

1108

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[56]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.52

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.37

upper limit

1.7

Notes
[56] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 15 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 33

Statistical analysis description

GMT Ratio

Comparison groups

20 to 26 Years of Age v Stage I: 9 to 15 Years of Age

Number of subjects included in analysis

1108

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[57]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.41

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.27

upper limit

1.56

Notes
[57] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 15 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 45

Statistical analysis description

GMT Ratio

Comparison groups

20 to 26 Years of Age v Stage I: 9 to 15 Years of Age

Number of subjects included in analysis

1108

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[58]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.64

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.46

upper limit

1.84

Notes
[58] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 15 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 52

Statistical analysis description

GMT Ratio

Comparison groups

20 to 26 Years of Age v Stage I: 9 to 15 Years of Age

Number of subjects included in analysis

1108

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[59]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.35

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.21

upper limit

1.49

Notes
[59] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 15 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Anti-HPV 58

Statistical analysis description

GMT Ratio

Comparison groups

20 to 26 Years of Age v Stage I: 9 to 15 Years of Age

Number of subjects included in analysis

1108

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[60]

P-value

< 0.0001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.44

Confidence interval

level

97.5%

sides

2-sided

lower limit

1.29

upper limit

1.6

Notes
[60] - Criterion for non-inferiority with respect to GMT ratio (females 9 to 15 years of age / females 20 to 26 years of age) required that the lower bound of 97.5% confidence be greater than 0.67 for each HPV type. An analysis of variance model with a response of log individual titers and fixed effect for group was used.

Secondary: Stage I: Percentage of Participants 9 to 15 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

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End point title

Stage I: Percentage of Participants 9 to 15 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

End point description

The percentage of participants who are seropositive for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 was determined using cLIA. Seroconversion was defined as changing serostatus from seronegative at baseline (Day 1) to seropositive at 1 month after last dose. Cutoff values for HPV seropositivity are ≥50, 29, 41, 59, 29, 22, 15, 20, and 15 mMU/mL for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, respectively. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Secondary

End point timeframe

1 month post vaccination 3 (Month 7)

End point values	Stage I: 9 to 15 Years of Age
Number of subjects analysed	458
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 ≥50 mMU/mL (n=426)	100.0 (99.1 to 100.0)
Anti-HPV 11 ≥29 mMU/mL (n=426)	100.0 (99.1 to 100.0)
Anti-HPV 16 ≥41 mMU/mL (n=441)	100.0 (99.2 to 100.0)
Anti-HPV 18 ≥59 mMU/mL (n=422)	100.0 (99.1 to 100.0)
Anti-HPV 31 ≥29 mMU/mL (n=436)	100.0 (99.2 to 100.0)
Anti-HPV 33 ≥22 mMU/mL (n=432)	100.0 (99.1 to 100.0)
Anti-HPV 45 ≥15 mMU/mL (n=437)	100.0 (99.2 to 100.0)
Anti-HPV 52 ≥20 mMU/mL (n=430)	100.0 (99.1 to 100.0)
Anti-HPV 58 ≥15 mMU/mL (n=429)	100.0 (99.1 to 100.0)

No statistical analyses for this end point

Secondary: Stage I: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 27 to 45 Years of Age: Month 7

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End point title

Stage I: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 27 to 45 Years of Age: Month 7 ^[61]

End point description

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined using cLIA. The HPV-9 cLIA assay was used to quantify the antibodies. This assay evaluated the serological response before and after 9vHPV vaccination and measured HPV infection-induced antibodies. The GMT for each HPV type were expressed as mMU/mL. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type and in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Secondary

End point timeframe

1 month post vaccination 3 (Month 7)

Notes
[61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analyses were planned for arms 1 and 2 for this endpoint.

End point values	27 to 45 Years of Age
Number of subjects analysed	650
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6 (n=517)	784.1 (738.9 to 832.1)
Anti-HPV 11 (n=517)	634.7 (596.1 to 675.8)
Anti-HPV 16 (n=575)	3175.0 (2983.0 to 3379.5)
Anti-HPV 18 (n=575)	838.9 (783.8 to 897.8)
Anti-HPV 31 (n=576)	699.9 (658.3 to 744.1)
Anti-HPV 33 (n=569)	422.7 (396.9 to 450.1)
Anti-HPV 45 (n=598)	245.1 (229.8 to 261.5)
Anti-HPV 52 (n=578)	342.1 (322.2 to 363.2)
Anti-HPV 58 (n=534)	435.2 (408.1 to 464.2)

No statistical analyses for this end point

Secondary: Stage I: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age, 20 to 26 Years of Age, and 27 to 45 Years of Age: Month 7

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End point title

Stage I: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age, 20 to 26 Years of Age, and 27 to 45 Years of Age: Month 7

End point description

Serum antibody titers for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined using IgG LIA. The HPV-9 IgG LIA assay was used to quantify the antibodies. This assay evaluated the serological response before and after 9vHPV vaccination and measured HPV infection-induced antibodies. The GMT for each HPV type was expressed as mMU/mL. Participants who 1) received all vaccinations in the planned regimen, 2) were seronegative at Day 1 for the relevant HPV type and in the analysis of HPV types 6 and 11, the participant must be seronegative to both HPV 6 and 11, 3) had a serum sample collected 1 month after last dose within an acceptable day range, and 4) had no other protocol violations that could interfere with the evaluation of participant’s immune response to the study vaccine were analyzed.

End point type

Secondary

End point timeframe

1 month post vaccination 3 (Month 7)

End point values	9 to 19 Years of Age	20 to 26 Years of Age	27 to 45 Years of Age
Number of subjects analysed	688	650	650
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV 6 (n=640, 567, 517)	1177.1 (1105.1 to 1253.7)	835.9 (785.7 to 889.3)	717.2 (668.3 to 769.8)
Anti-HPV 11 (n=640, 567, 517)	939.9 (884.2 to 999.1)	670.6 (628.8 to 715.2)	566.1 (526.0 to 609.1)
Anti-HPV 16 (n=662, 595, 575)	4746.8 (4473.9 to 5036.4)	3435.0 (3232.2 to 3650.5)	2867.6 (2685.8 to 3061.7)
Anti-HPV 18 (n=630, 574, 575)	1303.8 (1219.5 to 1393.8)	910.3 (848.6 to 976.5)	741.7 (690.6 to 796.5)
Anti-HPV 31 (n=657, 587, 576)	1082.5 (1016.4 to 1152.9)	744.2 (695.5 to 796.2)	630.2 (589.5 to 673.6)
Anti-HPV 33 (n=642, 589, 569)	647.1 (607.3 to 689.5)	461.7 (433.0 to 492.4)	384.5 (359.0 to 411.9)
Anti-HPV 45 (n=655, 598, 598)	397.9 (371.7 to 425.9)	260.7 (243.0 to 279.6)	213.7 (199.6 to 228.8)
Anti-HPV 52 (n=649, 572, 578)	478.8 (450.7 to 508.8)	354.7 (332.0 to 379.0)	278.3 (259.2 to 298.8)
Anti-HPV 58 (n=645, 580, 534)	698.8 (659.0 to 741.1)	501.0 (469.4 to 534.8)	399.3 (373.2 to 427.2)

No statistical analyses for this end point

Secondary: Stage I: Percentage of Participants 9 to 19 Years of Age, 20 to 26 Years of Age, and 27 to 45 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

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End point title

Stage I: Percentage of Participants 9 to 19 Years of Age, 20 to 26 Years of Age, and 27 to 45 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

End point description

End point type

Secondary

End point timeframe

1 month post vaccination 3 (Month 7)

End point values	9 to 19 Years of Age	20 to 26 Years of Age	27 to 45 Years of Age
Number of subjects analysed	688	650	650
Units: Percentage of Participants
number (confidence interval 95%)
Anti-HPV 6 ≥9 mMU/mL (n=640, 567, 517)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)	100.0 (99.3 to 100.0)
Anti-HPV 11 ≥6 mMU/mL (n=640, 567, 517)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)	100.0 (99.3 to 100.0)
Anti-HPV 16 ≥5 mMU/mL (n=662, 595, 575)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 18 ≥5 mMU/mL (n=630, 574, 575)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 31 ≥3 mMU/mL (n=657, 587, 576)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 33 ≥4 mMU/mL (n=642, 589, 569)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 45 ≥3 mMU/mL (n=655, 598, 598)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 52 ≥5 mMU/mL (n=649, 572, 578)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)
Anti-HPV 58 ≥5 mMU/mL (n=645, 580, 534)	100.0 (99.4 to 100.0)	100.0 (99.4 to 100.0)	100.0 (99.3 to 100.0)

No statistical analyses for this end point

Secondary: Stage I: Percentage of Participants Who Experience at Least 1 Solicited Injection-site Adverse Event (AE)

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End point title

Stage I: Percentage of Participants Who Experience at Least 1 Solicited Injection-site Adverse Event (AE)

End point description

An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. The participant or the parent/guardian of the participant were to record the presence of any vaccination report card (VRC)-prompted injection-site AEs that occurred in the 8 days after any vaccination. The percentage of participants with an injection-site AE prompted on the VRC (erythema, pain, swelling and induration) is reported. The analysis population consisted of all participants who received at least 1 dose of study vaccination.

End point type

Secondary

End point timeframe

Up to 8 days post any vaccination (Up to ~Day 192)

End point values	9 to 19 Years of Age	20 to 26 Years of Age	27 to 45 Years of Age
Number of subjects analysed	688	650	650
Units: Percentage of Participants
number (confidence interval 95%)
Injection site pain	39.1 (35.4 to 42.9)	44.5 (40.6 to 48.4)	39.1 (35.3 to 42.9)
Injection site erythema	9.3 (7.2 to 11.7)	11.1 (8.8 to 13.7)	7.4 (5.5 to 9.7)
Injection site swelling	8.1 (6.2 to 10.4)	8.9 (6.8 to 11.4)	5.4 (3.8 to 7.4)
Injection site induration	6.3 (4.6 to 8.3)	8.0 (6.0 to 10.4)	6.0 (4.3 to 8.1)

No statistical analyses for this end point

Secondary: Stage I: Percentage of Participants Who Experience at Least 1 Systemic AE

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End point title

Stage I: Percentage of Participants Who Experience at Least 1 Systemic AE

End point description

An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. The percentage of participants with a systemic AE is reported. The analysis population consisted of all participants who received at least 1 dose of study vaccination.

End point type

Secondary

End point timeframe

Up to 31 days post any vaccination (Up to ~Month 7)

End point values	9 to 19 Years of Age	20 to 26 Years of Age	27 to 45 Years of Age
Number of subjects analysed	688	650	650
Units: Percentage of Participants
number (confidence interval 95%)	50.9 (47.1 to 54.7)	57.1 (53.2 to 60.9)	43.4 (39.5 to 47.3)

No statistical analyses for this end point

Secondary: Stage I: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE)

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End point title

Stage I: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE)

End point description

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the study vaccine. An SAE is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, or is another important medical event. The percentage of participants that experienced 1 or more SAEs is reported. The analysis population consisted of all participants who received at least 1 dose of study vaccination.

End point type

Secondary

End point timeframe

Day 1 to Month 7

End point values	9 to 19 Years of Age	20 to 26 Years of Age	27 to 45 Years of Age
Number of subjects analysed	688	650	650
Units: Percentage of Participants
number (confidence interval 95%)	1.0 (0.4 to 2.1)	2.6 (1.5 to 4.2)	2.6 (1.5 to 4.2)

No statistical analyses for this end point

Secondary: Stage I: Percentage of Participants with Elevated Axillary Temperature (≥37.1 C)

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End point title

Stage I: Percentage of Participants with Elevated Axillary Temperature (≥37.1 C)

End point description

Participant or participant’s legally acceptable representative will be asked to record axillary temperature in the evening after each study vaccination and daily, at the same time of day whenever possible, for 8 days after each study vaccination in the VRC. The percentage of participant’s who had an axillary temperature ≥37.1°C is reported. The analysis population consisted of all participants who received at least 1 dose of study vaccination.

End point type

Secondary

End point timeframe

Up to 8 days post any vaccination (Up to ~Day 192)

End point values	9 to 19 Years of Age	20 to 26 Years of Age	27 to 45 Years of Age
Number of subjects analysed	688	650	650
Units: Percentage of Participants
number (confidence interval 95%)
≥37.1°C (98.8°F) and <37.6°C (99.7°F)	20.8 (17.8 to 24.0)	23.8 (20.6 to 27.3)	11.7 (9.3 to 14.4)
≥37.6°C (99.7°F) and <39.1°C (102.4°F)	2.2 (1.2 to 3.6)	2.0 (1.1 to 3.4)	0.5 (0.1 to 1.3)
≥39.1°C (102.4°F)	0.3 (0.0 to 1.0)	0.2 (0.0 to 0.9)	0.0 (0.0 to 0.6)

No statistical analyses for this end point

Secondary: Stage II: Percentage of Participants 9 to 19 years of Age Who Experience at Least 1 Serious Adverse Event (SAE): Month 7 to Month 60

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End point title

Stage II: Percentage of Participants 9 to 19 years of Age Who Experience at Least 1 Serious Adverse Event (SAE): Month 7 to Month 60

End point description

End point type

Secondary

End point timeframe

Month 7 to Month 60

End point values	9 to 19 Years of Age
Number of subjects analysed	682
Units: Percentage of Participants
number (not applicable)	1.5

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Stage I: Day 1 to Month 7; Stage II: Post Month 7 to Month 60

Adverse event reporting additional description

The analysis population for deaths (all-causes) included all enrolled participants (N=690, N=650, N=650, N=682). The analysis population for AEs included all enrolled participants who received at least 1 dose of study vaccination.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

28.0

Reporting group title

9 to 19 Years of Age Stage I

Reporting group description

Chinese females 9 to 19 years of age received a 0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Reporting group title

20 to 26 Years of Age Stage I

Reporting group description

Chinese females 20 to 26 years of age received a 0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Reporting group title

27 to 45 Years of Age Stage I

Reporting group description

Chinese females 27 to 45 years of age received a 0.5 mL per dose was administered as an intramuscular injection at Day 1, Month 2, and Month 6.

Reporting group title

9 to 19 Years of Age Stage II

Reporting group description

Participants in the 9 to 19 years of age group who completed 3 doses of V503 were eligible for Stage II and followed up to Month 60.

Serious adverse events	9 to 19 Years of Age Stage I	20 to 26 Years of Age Stage I	27 to 45 Years of Age Stage I	9 to 19 Years of Age Stage II
Total subjects affected by serious adverse events
subjects affected / exposed	9 / 688 (1.31%)	17 / 650 (2.62%)	17 / 650 (2.62%)	10 / 682 (1.47%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	1 / 650 (0.15%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nipple neoplasm
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	1 / 650 (0.15%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lipoma
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	0 / 650 (0.00%)	1 / 682 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fibroadenoma of breast
subjects affected / exposed	1 / 688 (0.15%)	3 / 650 (0.46%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	1 / 650 (0.15%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Abortion induced
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	1 / 650 (0.15%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Biochemical pregnancy
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abortion spontaneous
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abortion missed
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	2 / 650 (0.31%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ectopic pregnancy
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian cyst
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cervical dysplasia
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	2 / 650 (0.31%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abnormal uterine bleeding
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	0 / 650 (0.00%)	1 / 682 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian cyst ruptured
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	0 / 650 (0.00%)	1 / 682 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Uterine adhesions
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	1 / 650 (0.15%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Uterine polyp
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	1 / 650 (0.15%)	1 / 682 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Uterine diverticulum
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	2 / 650 (0.31%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Nasal polyps
subjects affected / exposed	1 / 688 (0.15%)	0 / 650 (0.00%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	1 / 650 (0.15%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Schizophrenia
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Closed globe injury
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Craniofacial fracture
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thoracic vertebral fracture
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	1 / 650 (0.15%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Supraventricular tachycardia
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	0 / 650 (0.00%)	1 / 682 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Immune thrombocytopenia
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	0 / 650 (0.00%)	1 / 682 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Retinal detachment
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	1 / 650 (0.15%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Embedded tooth
subjects affected / exposed	1 / 688 (0.15%)	0 / 650 (0.00%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enteritis
subjects affected / exposed	1 / 688 (0.15%)	0 / 650 (0.00%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	1 / 688 (0.15%)	0 / 650 (0.00%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemoperitoneum
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	1 / 650 (0.15%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inflammatory bowel disease
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	1 / 650 (0.15%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	0 / 650 (0.00%)	1 / 682 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tooth impacted
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	1 / 688 (0.15%)	0 / 650 (0.00%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic function abnormal
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	0 / 650 (0.00%)	1 / 682 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis chronic
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Bromhidrosis
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	0 / 650 (0.00%)	1 / 682 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Jaw cyst
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	1 / 650 (0.15%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chondropathy
subjects affected / exposed	1 / 688 (0.15%)	0 / 650 (0.00%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis perforated
subjects affected / exposed	1 / 688 (0.15%)	0 / 650 (0.00%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anal abscess
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea infectious
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymphadenitis bacterial
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tonsillitis bacterial
subjects affected / exposed	0 / 688 (0.00%)	0 / 650 (0.00%)	0 / 650 (0.00%)	1 / 682 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia mycoplasmal
subjects affected / exposed	1 / 688 (0.15%)	0 / 650 (0.00%)	0 / 650 (0.00%)	0 / 682 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 688 (0.00%)	1 / 650 (0.15%)	1 / 650 (0.15%)	1 / 682 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	9 to 19 Years of Age Stage I	20 to 26 Years of Age Stage I	27 to 45 Years of Age Stage I	9 to 19 Years of Age Stage II
Total subjects affected by non serious adverse events
subjects affected / exposed	411 / 688 (59.74%)	424 / 650 (65.23%)	346 / 650 (53.23%)	0 / 682 (0.00%)
General disorders and administration site conditions
Injection site erythema
subjects affected / exposed	64 / 688 (9.30%)	73 / 650 (11.23%)	48 / 650 (7.38%)	0 / 682 (0.00%)
occurrences all number	76	93	61	0
Injection site induration
subjects affected / exposed	46 / 688 (6.69%)	58 / 650 (8.92%)	45 / 650 (6.92%)	0 / 682 (0.00%)
occurrences all number	52	68	51	0
Injection site pain
subjects affected / exposed	270 / 688 (39.24%)	294 / 650 (45.23%)	259 / 650 (39.85%)	0 / 682 (0.00%)
occurrences all number	411	492	407	0
Injection site swelling
subjects affected / exposed	60 / 688 (8.72%)	63 / 650 (9.69%)	38 / 650 (5.85%)	0 / 682 (0.00%)
occurrences all number	69	72	48	0
Pyrexia
subjects affected / exposed	172 / 688 (25.00%)	175 / 650 (26.92%)	85 / 650 (13.08%)	0 / 682 (0.00%)
occurrences all number	256	261	117	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	51 / 688 (7.41%)	35 / 650 (5.38%)	27 / 650 (4.15%)	0 / 682 (0.00%)
occurrences all number	57	36	29	0
Oropharyngeal pain
subjects affected / exposed	45 / 688 (6.54%)	44 / 650 (6.77%)	22 / 650 (3.38%)	0 / 682 (0.00%)
occurrences all number	53	45	24	0
Rhinorrhoea
subjects affected / exposed	42 / 688 (6.10%)	40 / 650 (6.15%)	19 / 650 (2.92%)	0 / 682 (0.00%)
occurrences all number	46	44	19	0

More information

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Were there any global substantial amendments to the protocol? Yes

14 May 2020

Amendment 01: Primary reason for amendment was to extend the visit window of Dose 3 vaccination.

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 Open-Label Clinical Trial to Study the Immunogenicity and Safety of 9-Valent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine (V503) in Chinese females 9 to 45 Years of Age

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Stage I: Competitive Luminex Immunoassay (cLIA) Geometric Mean Titers (GMTs) for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age and 20 to 26 Years of Age: Month 7

Primary: Stage I: Competitive Luminex Immunoassay (cLIA) Geometric Mean Titers (GMTs) for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age and 20 to 26 Years of Age: Month 7

Primary: Stage I: Percentage of Participants 27 to 45 Years of Age and 20 to 26 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

Primary: Stage I: Percentage of Participants 27 to 45 Years of Age and 20 to 26 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age: Month 12

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age: Month 12

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 24

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 24

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 36

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 36

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 48

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 48

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 60

Primary: Stage II: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 60

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 12

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 12

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 24

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 24

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 36

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 36

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 48

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 48

Primary: Stage II: Percentage of Participants 9 to 19 years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 60

Primary: Stage II: Percentage of Participants 9 to 19 years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 60

Primary: Stage II: Immunoglobulin G Luminex Immunoassay (IgG LIA) GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 12

Primary: Stage II: Immunoglobulin G Luminex Immunoassay (IgG LIA) GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 12

Primary: Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 24

Primary: Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 24

Primary: Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 36

Primary: Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 36

Primary: Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 48

Primary: Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 48

Primary: Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 60

Primary: Stage II: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 years of Age: Month 60

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 12

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 12

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 24

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 24

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 36

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 36

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 48

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 48

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 60

Primary: Stage II: Percentage of Participants 9 to 19 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 60

Secondary: Stage I: Percentage of Participants 9 to 19 Years of Age and 20 to 26 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

Secondary: Stage I: Percentage of Participants 9 to 19 Years of Age and 20 to 26 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

Secondary: Stage I: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 15 Years of Age and 20 to 26 Years of Age: Month 7

Secondary: Stage I: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 15 Years of Age and 20 to 26 Years of Age: Month 7

Secondary: Stage I: Percentage of Participants 9 to 15 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

Secondary: Stage I: Percentage of Participants 9 to 15 Years of Age Who Are Seropositive by cLIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

Secondary: Stage I: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 27 to 45 Years of Age: Month 7

Secondary: Stage I: cLIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 27 to 45 Years of Age: Month 7

Secondary: Stage I: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age, 20 to 26 Years of Age, and 27 to 45 Years of Age: Month 7

Secondary: Stage I: IgG LIA GMTs for HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 in Participants 9 to 19 Years of Age, 20 to 26 Years of Age, and 27 to 45 Years of Age: Month 7

Secondary: Stage I: Percentage of Participants 9 to 19 Years of Age, 20 to 26 Years of Age, and 27 to 45 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

Secondary: Stage I: Percentage of Participants 9 to 19 Years of Age, 20 to 26 Years of Age, and 27 to 45 Years of Age Who Are Seropositive by IgG LIA to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58: Month 7

Secondary: Stage I: Percentage of Participants Who Experience at Least 1 Solicited Injection-site Adverse Event (AE)

Secondary: Stage I: Percentage of Participants Who Experience at Least 1 Solicited Injection-site Adverse Event (AE)

Secondary: Stage I: Percentage of Participants Who Experience at Least 1 Systemic AE

Secondary: Stage I: Percentage of Participants Who Experience at Least 1 Systemic AE

Secondary: Stage I: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE)

Secondary: Stage I: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE)

Secondary: Stage I: Percentage of Participants with Elevated Axillary Temperature (≥37.1 C)

Secondary: Stage I: Percentage of Participants with Elevated Axillary Temperature (≥37.1 C)

Secondary: Stage II: Percentage of Participants 9 to 19 years of Age Who Experience at Least 1 Serious Adverse Event (SAE): Month 7 to Month 60

Secondary: Stage II: Percentage of Participants 9 to 19 years of Age Who Experience at Least 1 Serious Adverse Event (SAE): Month 7 to Month 60

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Clinical Trial Results:
A Phase 3 Open-Label Clinical Trial to Study the Immunogenicity and Safety of 9-Valent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine (V503) in Chinese females 9 to 45 Years of Age