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Clinical Trial Results:
A Phase III Clinical Trial to Study the Tolerability and Immunogenicity of a 2-dose regimen of V503, a Multivalent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine, administered in Preadolescents and Adolescents (9 to 14 year olds) with a Comparison to Young Women (16 to 26 year olds)

Summary
EudraCT number	2013-001314-15
Trial protocol	CZ NO DK ES Outside EU/EEA
Global end of trial date	15 Sep 2017

Results information
Results version number	v1
This version publication date	09 Feb 2018
First version publication date	09 Feb 2018
Other versions	v2

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

V503-010

ISRCTN number

US NCT number

NCT01984697

WHO universal trial number (UTN)

Sponsor organisation name

Merck Sharp & Dohme Corp.

Sponsor organisation address

2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.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

15 Sep 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

15 Sep 2017

Was the trial ended prematurely?

Main objective of the trial

This study was a 37-month safety and immunogenicity study conducted in boys and girls 9 to 14 years of age and in young women 16 to 26 years of age. From this study, the goal was to establish that the investigational 2-dose regimens (0, 6 months and 0, 12 months) studied in boys and girls 9 to 14 years of age are generally safe and immunogenic, with an antibody response that is not inferior to that observed in young women 16 to 26 years of age who received the standard 3-dose regimen of V503 (i.e., the population and dose regimen used to establish V503 efficacy).

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

12 Dec 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 116

Country: Number of subjects enrolled

Chile: 95

Country: Number of subjects enrolled

Colombia: 151

Country: Number of subjects enrolled

Czech Republic: 116

Country: Number of subjects enrolled

Denmark: 132

Country: Number of subjects enrolled

Israel: 62

Country: Number of subjects enrolled

Korea, Republic of: 46

Country: Number of subjects enrolled

Malaysia: 72

Country: Number of subjects enrolled

Norway: 106

Country: Number of subjects enrolled

South Africa: 107

Country: Number of subjects enrolled

Spain: 116

Country: Number of subjects enrolled

Taiwan: 42

Country: Number of subjects enrolled

Thailand: 76

Country: Number of subjects enrolled

Turkey: 22

Country: Number of subjects enrolled

United States: 259

Worldwide total number of subjects

1518

EEA total number of subjects

470

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)

606

Adolescents (12-17 years)

633

Adults (18-64 years)

279

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

A total of 1536 participants were screened and 1518 were randomized into the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Girls 9 to 14 Years V503 at Months 0 and 6

Arm description

Girls aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL intramuscular (IM) injection at Months 0 and 6.

Arm type

Experimental

Investigational medicinal product name

V503

Investigational medicinal product code

Other name

9-valent (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL IM injection at Months 0 and 6 (initial 2-dose regimen)

Boys 9 to 14 Years V503 at Months 0 and 6

Arm description

Boys aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL IM injection at Months 0 and 6.

Arm type

Experimental

Investigational medicinal product name

V503

Investigational medicinal product code

Other name

9-valent (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL IM injection at Months 0 and 6 (initial 2-dose regimen)

Girls and Boys 9 to 14 Years V503 at Months 0 and 12

Arm description

Girls and boys aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL IM injection at Months 0 and 12.

Arm type

Experimental

Investigational medicinal product name

V503

Investigational medicinal product code

Other name

9-valent (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL IM injection at Months 0 and 12 (initial 2-dose regimen)

Girls 9 to 14 Years V503 at Months 0, 2, and 6

Arm description

Girls aged 9 to 14 years received a 3-dose regimen of V503 0.5 mL IM injection at Months 0, 2, and 6.

Arm type

Experimental

Investigational medicinal product name

V503

Investigational medicinal product code

Other name

9-valent (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL IM injection at Months 0, 2, and 6 (initial 3-dose regimen)

Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Arm description

Young Women aged 16 to 26 years received a 3-dose regimen of V503 0.5 mL IM injection at Months 0, 2, and 6.

Arm type

Active comparator

Investigational medicinal product name

V503

Investigational medicinal product code

Other name

9-valent (Types 6, 11, 16, 18, 31, 33, 45, 52, 58) Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] vaccine

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL IM injection at Months 0, 2, and 6 (initial 3-dose regimen)

Number of subjects in period 1	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Started	301	301	301	301	314
Vaccination 1	301	301	300	300	314
Vaccination 2	293	296	291	298	313
Vaccination 3	0 ^[1]	0 ^[2]	0 ^[3]	293	311
Month 36 Vaccination	270	281	280	9 ^[4]	31 ^[5]
Completed	258	270	272	280	279
Not completed	43	31	29	21	35
Consent withdrawn by subject	15	21	13	11	13
Physician decision	3	-	-	1	-
Adverse event, non-fatal	-	-	2	-	-
Death	-	-	-	1	-
Pregnancy	2	-	1	-	1
Missed last follow-up visit	1	-	-	-	-
Lost to follow-up	14	5	10	6	21
Protocol deviation	8	5	3	2	-

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants in this group did not received Vaccination 3 per protocol
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants in this group did not received Vaccination 3 per protocol
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Participants in this group did not received Vaccination 3 per protocol
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: A total of 9 participants in this group received the Month 36 vaccination
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: A total of 31 participants in this group received the Month 36 vaccination

Baseline characteristics

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Reporting group title

Girls 9 to 14 Years V503 at Months 0 and 6

Reporting group description

Girls aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL intramuscular (IM) injection at Months 0 and 6.

Reporting group title

Boys 9 to 14 Years V503 at Months 0 and 6

Reporting group description

Boys aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL IM injection at Months 0 and 6.

Reporting group title

Girls and Boys 9 to 14 Years V503 at Months 0 and 12

Reporting group description

Girls and boys aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL IM injection at Months 0 and 12.

Reporting group title

Girls 9 to 14 Years V503 at Months 0, 2, and 6

Reporting group description

Girls aged 9 to 14 years received a 3-dose regimen of V503 0.5 mL IM injection at Months 0, 2, and 6.

Reporting group title

Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Reporting group description

Young Women aged 16 to 26 years received a 3-dose regimen of V503 0.5 mL IM injection at Months 0, 2, and 6.

Reporting group values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6	Total
Number of subjects	301	301	301	301	314	1518
Age, Customized
Units: Subjects
Between 9 and 10 years	100	98	100	101	0	399
Between 11 and 12 years	102	102	106	100	0	410
Between 13 and 14 years	99	101	95	100	0	395
Between 16 and 26 years	0	0	0	0	314	314
Age Continuous
Units: Years
arithmetic mean (standard deviation)	11.4 ( 1.7 )	11.5 ( 1.7 )	11.4 ( 1.6 )	11.4 ( 1.7 )	21.0 ( 2.7 )	-
Gender, Male/Female
Units: Subjects
Female	301	0	151	301	314	1067
Male	0	301	150	0	0	451

End points

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Reporting group title

Girls 9 to 14 Years V503 at Months 0 and 6

Reporting group description

Girls aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL intramuscular (IM) injection at Months 0 and 6.

Reporting group title

Boys 9 to 14 Years V503 at Months 0 and 6

Reporting group description

Boys aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL IM injection at Months 0 and 6.

Reporting group title

Girls and Boys 9 to 14 Years V503 at Months 0 and 12

Reporting group description

Girls and boys aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL IM injection at Months 0 and 12.

Reporting group title

Girls 9 to 14 Years V503 at Months 0, 2, and 6

Reporting group description

Girls aged 9 to 14 years received a 3-dose regimen of V503 0.5 mL IM injection at Months 0, 2, and 6.

Reporting group title

Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Reporting group description

Young Women aged 16 to 26 years received a 3-dose regimen of V503 0.5 mL IM injection at Months 0, 2, and 6.

Primary: Geometric Mean Titers to HPV Type 6 at Four Weeks After the Last Dose of V503

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End point title

Geometric Mean Titers to HPV Type 6 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV virus-like particles (VLP) type 6 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Primary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	258	263	257	254	238
Units: mMU/mL
geometric mean (confidence interval 95%)	1657.9 (1479.6 to 1857.6)	1557.4 (1391.5 to 1743.1)	2678.8 (2390.2 to 3002.1)	1496.1 (1334.1 to 1677.8)	770.9 (684.8 to 867.9)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

496

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT ratio

Point estimate

2.15

Confidence interval

level

95%

sides

2-sided

lower limit

1.83

upper limit

2.53

Notes
[1] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the Geometric Mean Titer (GMT) ratio for Girls 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

501

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

2.02

Confidence interval

level

95%

sides

2-sided

lower limit

1.73

upper limit

2.36

Notes
[2] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

495

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

3.47

Confidence interval

level

95%

sides

2-sided

lower limit

2.93

upper limit

4.11

Notes
[3] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls and Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Primary: Geometric Mean Titers to HPV Type 11 at Four Weeks After the Last Dose of V503

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End point title

Geometric Mean Titers to HPV Type 11 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 11 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Primary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	258	264	257	254	238
Units: mMU/mL
geometric mean (confidence interval 95%)	1388.9 (1240.4 to 1555.3)	1423.9 (1273.2 to 1592.3)	2941.8 (2626.6 to 3294.9)	1306.3 (1165.5 to 1464.0)	580.5 (516.0 to 653.0)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

496

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT ratio

Point estimate

2.39

Confidence interval

level

95%

sides

2-sided

lower limit

2.03

upper limit

2.82

Notes
[4] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

502

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

2.45

Confidence interval

level

95%

sides

2-sided

lower limit

2.09

upper limit

2.88

Notes
[5] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

495

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

5.07

Confidence interval

level

95%

sides

2-sided

lower limit

4.32

upper limit

5.94

Notes
[6] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls and Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Primary: Geometric Mean Titers to HPV Type 16 at Four Weeks After the Last Dose of V503

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End point title

Geometric Mean Titers to HPV Type 16 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 16 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Primary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	272	273	264	269	249
Units: mMU/mL
geometric mean (confidence interval 95%)	8004.9 (7160.5 to 8948.8)	8474.8 (7582.4 to 9472.3)	14329.3 (12796.4 to 16045.9)	6996.0 (6254.1 to 7825.8)	3154.0 (2807.1 to 3543.7)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT ratio

Point estimate

2.54

Confidence interval

level

95%

sides

2-sided

lower limit

2.14

upper limit

Notes
[7] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

522

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

2.69

Confidence interval

level

95%

sides

2-sided

lower limit

2.29

upper limit

3.15

Notes
[8] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

513

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

4.54

Confidence interval

level

95%

sides

2-sided

lower limit

3.84

upper limit

5.37

Notes
[9] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls and Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Primary: Geometric Mean Titers to HPV Type 18 at Four Weeks After the Last Dose of V503

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End point title

Geometric Mean Titers to HPV Type 18 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 18 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Primary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	272	272	266	270	267
Units: mMU/mL
geometric mean (confidence interval 95%)	1872.8 (1651.6 to 2123.6)	1860.9 (1641.1 to 2110.2)	2810.4 (2474.9 to 3191.3)	2049.3 (1806.4 to 2324.8)	761.5 (670.8 to 864.5)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

539

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT ratio

Point estimate

2.46

Confidence interval

level

95%

sides

2-sided

lower limit

2.05

upper limit

2.96

Notes
[10] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

539

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

2.44

Confidence interval

level

95%

sides

2-sided

lower limit

2.04

upper limit

2.92

Notes
[11] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

533

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[12]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

3.69

Confidence interval

level

95%

sides

2-sided

lower limit

3.06

upper limit

4.45

Notes
[12] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls and Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Primary: Geometric Mean Titers to HPV Type 31 at Four Weeks After the Last Dose of V503

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End point title

Geometric Mean Titers to HPV Type 31 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 31 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Primary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	272	271	268	271	264
Units: mMU/mL
geometric mean (confidence interval 95%)	1436.3 (1272.1 to 1621.8)	1498.2 (1326.5 to 1692.0)	2117.5 (1873.7 to 2393.1)	1748.3 (1548.1 to 1974.5)	572.1 (505.8 to 647.2)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

536

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[13]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT ratio

Point estimate

2.51

Confidence interval

level

95%

sides

2-sided

lower limit

2.1

upper limit

Notes
[13] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[14]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

2.62

Confidence interval

level

95%

sides

2-sided

lower limit

2.2

upper limit

3.12

Notes
[14] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

532

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[15]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

3.7

Confidence interval

level

95%

sides

2-sided

lower limit

3.08

upper limit

4.45

Notes
[15] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls and Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Primary: Geometric Mean Titers to HPV Type 33 at Four Weeks After the Last Dose of V503

Top of page

End point title

Geometric Mean Titers to HPV Type 33 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 33 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Primary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	273	271	269	275	279
Units: mMU/mL
geometric mean (confidence interval 95%)	1030.0 (920.4 to 1152.7)	1040.0 (928.9 to 1164.3)	2197.5 (1961.9 to 2461.3)	796.4 (712.0 to 890.9)	348.1 (311.5 to 389.1)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

552

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[16]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT ratio

Point estimate

2.96

Confidence interval

level

95%

sides

2-sided

lower limit

2.5

upper limit

3.5

Notes
[16] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

550

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[17]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

2.99

Confidence interval

level

95%

sides

2-sided

lower limit

2.55

upper limit

3.5

Notes
[17] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

548

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[18]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

6.31

Confidence interval

level

95%

sides

2-sided

lower limit

5.36

upper limit

7.43

Notes
[18] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls and Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Primary: Geometric Mean Titers to HPV Type 45 at Four Weeks After the Last Dose of V503

Top of page

End point title

Geometric Mean Titers to HPV Type 45 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 45 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Primary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	274	273	268	275	280
Units: mMU/mL
geometric mean (confidence interval 95%)	357.6 (313.7 to 407.6)	352.3 (309.0 to 401.7)	417.7 (365.9 to 476.9)	661.7 (580.6 to 754.1)	213.6 (187.7 to 243.2)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT ratio

Point estimate

1.67

Confidence interval

level

95%

sides

2-sided

lower limit

1.38

upper limit

2.03

Notes
[19] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

553

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[20]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.65

Confidence interval

level

95%

sides

2-sided

lower limit

1.37

upper limit

1.99

Notes
[20] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

548

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.96

Confidence interval

level

95%

sides

2-sided

lower limit

1.61

upper limit

2.37

Notes
[21] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls and Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Primary: Geometric Mean Titers to HPV Type 52 at Four Weeks After the Last Dose of V503

Top of page

End point title

Geometric Mean Titers to HPV Type 52 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 52 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Primary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	272	273	268	275	271
Units: mMU/mL
geometric mean (confidence interval 95%)	581.1 (521.9 to 647.1)	640.4 (575.2 to 713.0)	1123.4 (1008.1 to 1251.9)	909.9 (817.6 to 1012.5)	364.2 (327.0 to 405.6)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

543

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[22]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT ratio

Point estimate

1.6

Confidence interval

level

95%

sides

2-sided

lower limit

1.36

upper limit

1.87

Notes
[22] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

544

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[23]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

1.76

Confidence interval

level

95%

sides

2-sided

lower limit

1.51

upper limit

2.05

Notes
[23] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

539

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[24]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

3.08

Confidence interval

level

95%

sides

2-sided

lower limit

2.64

upper limit

3.61

Notes
[24] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls and Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Primary: Geometric Mean Titers to HPV Type 58 at Four Weeks After the Last Dose of V503

Top of page

End point title

Geometric Mean Titers to HPV Type 58 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 58 were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Primary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	270	270	265	273	261
Units: mMU/mL
geometric mean (confidence interval 95%)	1251.2 (1119.6 to 1398.4)	1325.7 (1186.2 to 1481.6)	2444.6 (2185.2 to 2734.9)	1229.3 (1100.7 to 1373.0)	491.1 (438.6 to 549.8)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

531

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[25]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT ratio

Point estimate

2.55

Confidence interval

level

95%

sides

2-sided

lower limit

2.15

upper limit

3.01

Notes
[25] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

531

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[26]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

2.7

Confidence interval

level

95%

sides

2-sided

lower limit

2.3

upper limit

3.16

Notes
[26] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

526

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[27]

P-value

< 0.001

Method

ANOVA

Parameter type

GMT Ratio

Point estimate

4.98

Confidence interval

level

95%

sides

2-sided

lower limit

4.23

upper limit

5.86

Notes
[27] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the GMT ratio for Girls and Boys 9 to 14 Years / Young Women 16 to 26 years is >0.67.

Secondary: Percentage of Participants with Seroconversion to HPV Type 6 at Four Weeks After the Last Dose of V503

Top of page

End point title

Percentage of Participants with Seroconversion to HPV Type 6 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 6 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 6 was defined as a titer >=30 mMU/mL. The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Secondary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	258	263	257	254	238
Units: Percentage of participants
number (confidence interval 95%)	99.6 (97.9 to 100)	100 (98.6 to 100)	100 (98.6 to 100)	99.2 (97.2 to 99.9)	99.6 (97.7 to 100)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

496

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[28]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

Notes
[28] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

501

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[29]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

2.3

Notes
[29] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

495

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[30]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

2.3

Notes
[30] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls and Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Secondary: Percentage of Participants with Seroconversion to HPV Type 11 at Four Weeks After the Last Dose of V503

Top of page

End point title

Percentage of Participants with Seroconversion to HPV Type 11 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 11 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 11 was defined as a titer >=16 mMU/mL. The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Secondary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	258	264	257	254	238
Units: Percentage of participants
number (confidence interval 95%)	100 (98.6 to 100)	100 (98.6 to 100)	100 (98.6 to 100)	99.6 (97.8 to 100)	99.6 (97.7 to 100)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

496

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[31]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

2.3

Notes
[31] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

502

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[32]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

2.3

Notes
[32] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

495

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[33]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

2.3

Notes
[33] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls and Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Secondary: Percentage of Participants with Seroconversion to HPV Type 16 at Four Weeks After the Last Dose of V503

Top of page

End point title

Percentage of Participants with Seroconversion to HPV Type 16 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 16 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 16 was defined as a titer >=20 mMU/mL. The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Secondary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	272	273	264	269	249
Units: Percentage of participants
number (confidence interval 95%)	100 (98.7 to 100)	100 (98.7 to 100)	100 (98.6 to 100)	100 (98.6 to 100)	99.6 (97.8 to 100)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

521

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[34]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

2.2

Notes
[34] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

522

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[35]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

2.2

Notes
[35] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

513

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[36]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

2.2

Notes
[36] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls and Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Secondary: Percentage of Participants with Seroconversion to HPV Type 18 at Four Weeks After the Last Dose of V503

Top of page

End point title

Percentage of Participants with Seroconversion to HPV Type 18 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 18 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 18 was defined as a titer >=24 mMU/mL. The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Secondary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	272	272	266	270	267
Units: Percentage of participants
number (confidence interval 95%)	100 (98.7 to 100)	100 (98.7 to 100)	100 (98.6 to 100)	99.6 (98.0 to 100)	98.5 (96.2 to 99.6)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

539

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[37]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

3.8

Notes
[37] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

539

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[38]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

3.8

Notes
[38] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

533

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[39]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

3.8

Notes
[39] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls and Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Secondary: Percentage of Participants with Seroconversion to HPV Type 31 at Four Weeks After the Last Dose of V503

Top of page

End point title

Percentage of Participants with Seroconversion to HPV Type 31 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 31 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 31 was defined as a titer >=10 mMU/mL. The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Secondary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	272	271	268	271	264
Units: Percentage of participants
number (confidence interval 95%)	99.6 (98.0 to 100)	100 (98.6 to 100)	100 (98.6 to 100)	100 (98.6 to 100)	99.6 (97.9 to 100)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

536

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[40]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

1.8

Notes
[40] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

535

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[41]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

2.1

Notes
[41] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

532

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[42]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

2.1

Notes
[42] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls and Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Secondary: Percentage of Participants with Seroconversion to HPV Type 33 at Four Weeks After the Last Dose of V503

Top of page

End point title

Percentage of Participants with Seroconversion to HPV Type 33 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 33 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 33 was defined as a titer >=8 mMU/mL. The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Secondary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	273	271	269	275	279
Units: Percentage of participants
number (confidence interval 95%)	99.6 (98.0 to 100)	100 (98.6 to 100)	100 (98.6 to 100)	100 (98.7 to 100)	99.6 (98.0 to 100)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

552

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[43]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

1.7

Notes
[43] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

550

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[44]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

Notes
[44] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

548

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[45]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

Notes
[45] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls and Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Secondary: Percentage of Participants with Seroconversion to HPV Type 45 at Four Weeks After the Last Dose of V503

Top of page

End point title

Percentage of Participants with Seroconversion to HPV Type 45 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 45 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 45 was defined as a titer >=8 mMU/mL. The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Secondary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	274	273	268	275	280
Units: Percentage of participants
number (confidence interval 95%)	99.3 (97.4 to 99.9)	99.3 (97.4 to 99.9)	100 (98.6 to 100)	99.3 (97.4 to 99.9)	97.9 (95.4 to 99.2)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

554

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[46]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

Notes
[46] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

553

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[47]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

Notes
[47] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

548

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[48]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

2.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

4.6

Notes
[48] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls and Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Secondary: Percentage of Participants with Seroconversion to HPV Type 52 at Four Weeks After the Last Dose of V503

Top of page

End point title

Percentage of Participants with Seroconversion to HPV Type 52 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 52 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 52 was defined as a titer >=8 mMU/mL. The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Secondary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	272	273	268	275	271
Units: Percentage of participants
number (confidence interval 95%)	99.6 (98.0 to 100)	100 (98.7 to 100)	100 (98.6 to 100)	99.6 (98.0 to 100)	99.6 (98.0 to 100)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

543

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[49]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

1.7

Notes
[49] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

544

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[50]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

2.1

Notes
[50] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

539

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[51]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

2.1

Notes
[51] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls and Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Secondary: Percentage of Participants with Seroconversion to HPV Type 58 at Four Weeks After the Last Dose of V503

Top of page

End point title

Percentage of Participants with Seroconversion to HPV Type 58 at Four Weeks After the Last Dose of V503

End point description

Antibodies to HPV VLP type 58 were measured using a competitive Luminex immunoassay. Seroconversion to HPV type 58 was defined as a titer >=8 mMU/mL. The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Secondary

End point timeframe

4 weeks after the last dose of V503 (Month 7 or Month 13)

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	270	270	265	273	261
Units: Percentage of participants
number (confidence interval 95%)	100 (98.6 to 100)	100 (98.6 to 100)	100 (98.6 to 100)	99.6 (98.0 to 100)	99.6 (97.9 to 100)

Non-inferiority

Comparison groups

Girls 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

531

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[52]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

2.1

Notes
[52] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Boys 9 to 14 Years V503 at Months 0 and 6 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

531

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[53]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

2.1

Notes
[53] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Non-inferiority

Comparison groups

Girls and Boys 9 to 14 Years V503 at Months 0 and 12 v Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Number of subjects included in analysis

526

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[54]

P-value

< 0.001

Method

Miettinen and Nurminen

Parameter type

Seroconversion percentage difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.1

upper limit

2.1

Notes
[54] - Non-inferiority is demonstrated if the lower limit of the 95% confidence interval of the seroconversion percentage difference for Girls and Boys 9 to 14 Years - Young Women 16 to 26 years is > -5.

Other pre-specified: Antibody Persistence: Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 24

Top of page

End point title

Antibody Persistence: Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 24

End point description

Antibodies to HPV VLP types were measured using a competitive Luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Other pre-specified

End point timeframe

Month 24

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	301	301	300	300	314
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV Type 6 (n=253, 259, 252, 249, 232)	260.7 (231.5 to 293.6)	209.1 (185.9 to 235.1)	574.0 (509.6 to 646.5)	300.7 (266.8 to 339.0)	153.2 (135.4 to 173.5)
Anti-HPV Type 11 (n=253, 260, 252, 249, 232)	169.8 (150.5 to 191.7)	150.6 (133.6 to 169.7)	443.7 (392.9 to 501.0)	201.9 (178.7 to 228.1)	98.3 (86.6 to 111.6)
Anti-HPV Type 16 (n=266, 269, 259, 264, 241)	900.5 (788.0 to 1028.9)	801.0 (701.5 to 914.6)	2316.2 (2023.5 to 2651.4)	1041.3 (910.8 to 1190.4)	461.6 (401.2 to 531.0)
Anti-HPV Type 18 (n=266, 268, 261, 265, 259)	196.8 (174.9 to 221.6)	169.6 (150.7 to 190.8)	380.8 (337.9 to 429.1)	255.8 (227.2 to 288.0)	122.2 (108.4 to 137.7)
Anti-HPV Type 31 (n=266, 267, 263, 266, 258)	160.6 (140.8 to 183.3)	139.1 (122.0 to 158.7)	312.8 (273.9 to 357.1)	260.6 (228.4 to 297.3)	89.6 (78.4 to 102.5)
Anti-HPV Type 33 (n=267, 267, 264, 270, 269)	131.2 (116.9 to 147.2)	121.5 (108.3 to 136.4)	341.7 (304.3 to 383.6)	120.8 (107.7 to 135.4)	61.3 (54.6 to 68.7)
Anti-HPV Type 45 (n=268, 269, 263, 270, 271)	37.8 (33.2 to 43.0)	31.9 (28.0 to 36.3)	62.3 (54.7 to 71.1)	86.9 (76.4 to 98.9)	30.7 (27.0 to 34.9)
Anti-HPV Type 52 (n=266, 269, 263, 270, 261)	85.1 (76.4 to 94.7)	80.9 (72.7 to 90.0)	199.4 (179.0 to 222.2)	150.4 (135.2 to 167.4)	73.7 (66.1 to 82.1)
Anti-HPV Type 58 (n=264, 266, 260, 268, 253)	155.4 (138.0 to 175.1)	149.8 (133.1 to 168.6)	380.2 (337.3 to 428.6)	183.7 (163.3 to 206.7)	76.8 (68.0 to 86.7)

No statistical analyses for this end point

Other pre-specified: Antibody Persistence: Percentage of Participants with Seroconversion to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 24

Top of page

End point title

Antibody Persistence: Percentage of Participants with Seroconversion to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 24

End point description

Antibodies to HPV VLP types were measured using a competitive Luminex immunoassay. Seroconversion to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 were defined as a titer >=41, 24, 34, 38, 24, 18, 12, 16, and 12 mMU/mL, respectively. The per-protocol population included all participants who 1) received all vaccinations in the planned regimen, 2) had a serum sample collected 4 weeks after the last vaccination in the planned regimen, 3) were seronegative at Day 1 for the relevant HPV type, and 4) had no protocol violations that would interfere with evaluation of the immune response.

End point type

Other pre-specified

End point timeframe

Month 24

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	301	301	300	300	314
Units: Percentage of participants
number (confidence interval 95%)
Anti-HPV Type 6 (n=253, 259, 252, 249, 232)	98.4 (96.0 to 99.6)	96.9 (94.0 to 98.7)	99.2 (97.2 to 99.9)	99.6 (97.8 to 100)	94.0 (90.1 to 96.7)
Anti-HPV Type 11 (n=253, 260, 252, 249, 232)	98.0 (95.4 to 99.4)	95.8 (92.6 to 97.9)	99.6 (97.8 to 100)	98.8 (96.5 to 99.8)	94.8 (91.1 to 97.3)
Anti-HPV Type 16 (n=266, 269, 259, 264, 241)	98.9 (96.7 to 99.8)	99.6 (97.9 to 100)	100 (98.6 to 100)	99.6 (97.9 to 100)	99.6 (97.7 to 100)
Anti-HPV Type 18 (n=266, 268, 261, 265, 259)	98.5 (96.2 to 99.6)	95.9 (92.8 to 97.9)	98.9 (96.7 to 99.8)	99.2 (97.3 to 99.9)	95.0 (91.6 to 97.3)
Anti-HPV Type 31 (n=266, 267, 263, 266, 258)	97.0 (94.2 to 98.7)	94.8 (91.4 to 97.1)	98.5 (96.2 to 99.6)	97.7 (95.2 to 99.2)	91.5 (87.4 to 94.6)
Anti-HPV Type 33 (n=267, 267, 264, 270, 269)	97.8 (95.2 to 99.2)	96.6 (93.7 to 98.4)	99.2 (97.3 to 99.9)	98.9 (96.8 to 99.8)	94.8 (91.4 to 97.1)
Anti-HPV Type 45 (n=268, 269, 263, 270, 271)	88.4 (84.0 to 92.0)	85.9 (81.1 to 89.8)	93.9 (90.3 to 96.5)	96.7 (93.8 to 98.5)	82.7 (77.6 to 87.0)
Anti-HPV Type 52 (n=266, 269, 263, 270, 261)	96.6 (93.7 to 98.4)	95.2 (91.9 to 97.4)	99.2 (97.3 to 99.9)	99.3 (97.3 to 99.9)	97.3 (94.6 to 98.9)
Anti-HPV Type 58 (n=264, 266, 260, 268, 253)	98.9 (96.7 to 99.8)	99.6 (97.9 to 100)	100 (98.6 to 100)	100 (98.6 to 100)	96.0 (92.9 to 98.1)

No statistical analyses for this end point

Other pre-specified: Antibody Persistence: Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 36

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End point title

Antibody Persistence: Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 36

End point description

End point type

Other pre-specified

End point timeframe

Month 36

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	301	301	300	300	314
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV Type 6 (n=236, 254, 246, 240, 214)	209.6 (184.9 to 237.6)	160.1 (141.9 to 180.7)	401.2 (354.8 to 453.7)	232.2 (205.1 to 263.0)	133.8 (117.3 to 152.7)
Anti-HPV Type 11 (n=236, 255, 246, 240, 214)	133.7 (117.6 to 152.1)	115.2 (101.8 to 130.3)	308.2 (271.8 to 349.6)	159.1 (140.0 to 180.7)	82.9 (72.4 to 94.9)
Anti-HPV Type 16 (n=248, 263, 253, 255, 222)	673.8 (582.8 to 779.1)	592.6 (514.7 to 682.4)	1534.3 (1328.8 to 1771.5)	792.4 (686.7 to 914.4)	368.9 (316.4 to 430.0)
Anti-HPV Type 18 (n=248, 262, 255, 256, 239)	158.9 (140.8 to 179.4)	141.7 (125.9 to 159.4)	276.4 (245.3 to 311.6)	206.5 (183.3 to 232.7)	104.1 (92.0 to 117.8)
Anti-HPV Type 31 (n=248, 261, 257, 258, 235)	127.8 (111.4 to 146.5)	106.9 (93.5 to 122.1)	218.0 (190.6 to 249.4)	205.9 (180.0 to 235.5)	74.6 (64.8 to 85.9)
Anti-HPV Type 33 (n=249, 261, 258, 261, 246)	106.0 (94.1 to 119.5)	95.7 (85.1 to 107.5)	240.4 (213.8 to 270.3)	95.5 (85.0 to 107.3)	52.2 (46.3 to 58.9)
Anti-HPV Type 45 (n=250, 263, 257, 261, 248)	30.6 (26.9 to 35.0)	26.8 (23.6 to 30.4)	43.6 (38.3 to 49.7)	66.1 (58.1 to 75.2)	27.3 (23.9 to 31.1)
Anti-HPV Type 52 (n=248, 263, 257, 261, 239)	66.2 (59.1 to 74.0)	63.4 (56.8 to 70.7)	143.2 (128.3 to 159.9)	115.9 (103.9 to 129.3)	61.5 (54.8 to 68.9)
Anti-HPV Type 58 (n=246, 261, 255, 259, 231)	125.8 (111.1 to 142.5)	119.2 (105.6 to 134.5)	265.3 (234.8 to 299.8)	143.0 (126.7 to 161.5)	64.7 (56.9 to 73.6)

No statistical analyses for this end point

Other pre-specified: Antibody Persistence: Percentage of Participants with Seroconversion to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 36

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End point title

Antibody Persistence: Percentage of Participants with Seroconversion to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 36

End point description

End point type

Other pre-specified

End point timeframe

Month 36

End point values	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Number of subjects analysed	301	301	300	300	314
Units: mMU/mL
geometric mean (confidence interval 95%)
Anti-HPV Type 6 (n=236, 254, 246, 240, 214)	95.3 (91.8 to 97.7)	91.3 (87.2 to 94.5)	99.2 (97.1 to 99.9)	97.9 (95.2 to 99.3)	92.1 (87.6 to 95.3)
Anti-HPV Type 11 (n=236, 255, 246, 240, 214)	94.1 (90.2 to 96.7)	92.9 (89.1 to 95.8)	99.2 (97.1 to 99.9)	98.8 (96.4 to 99.7)	92.1 (87.6 to 95.3)
Anti-HPV Type 16 (n=248, 263, 253, 255, 222)	97.2 (94.3 to 98.9)	98.5 (96.2 to 99.6)	100 (98.6 to 100)	99.2 (97.2 to 99.9)	98.2 (95.5 to 99.5)
Anti-HPV Type 18 (n=248, 262, 255, 256, 239)	95.6 (92.2 to 97.8)	94.3 (90.7 to 96.8)	97.6 (94.9 to 99.1)	97.3 (94.4 to 98.9)	90.8 (86.4 to 94.1)
Anti-HPV Type 31 (n=248, 261, 257, 258, 235)	94.0 (90.2 to 96.6)	91.2 (87.1 to 94.3)	96.5 (93.5 to 98.4)	97.7 (95.0 to 99.1)	86.0 (80.8 to 90.1)
Anti-HPV Type 33 (n=249, 261, 258, 261, 246)	94.0 (90.3 to 96.6)	96.9 (94.1 to 98.7)	99.2 (97.2 to 99.9)	98.1 (95.6 to 99.4)	91.9 (87.7 to 95.0)
Anti-HPV Type 45 (n=250, 263, 257, 261, 248)	83.6 (78.4 to 88.0)	81.4 (76.1 to 85.9)	87.9 (83.3 to 91.7)	91.2 (87.1 to 94.3)	77.8 (72.1 to 82.8)
Anti-HPV Type 52 (n=248, 263, 257, 261, 239)	93.5 (89.7 to 96.3)	93.9 (90.3 to 96.5)	98.8 (96.6 to 99.8)	97.7 (95.1 to 99.2)	95.0 (91.4 to 97.4)
Anti-HPV Type 58 (n=246, 261, 255, 259, 231)	98.0 (95.3 to 99.3)	99.2 (97.3 to 99.9)	100 (98.6 to 100)	98.8 (96.7 to 99.8)	94.8 (91.1 to 97.3)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Serious Adverse Events: Up to Month 37; Non-injection site adverse events: up to Day 15 following any vaccination; Injection site adverse events: up to Day 5 following any vaccination

Adverse event reporting additional description

Participants at risk for adverse events includes those who were vaccinated and had safety follow-up data

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

Girls 9 to 14 Years V503 at Months 0 and 6

Reporting group description

Girls aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL intramuscular (IM) injection at Months 0 and 6. A challenge dose of V503 0.5 mL IM injection was administered at Month 36.

Reporting group title

Boys 9 to 14 Years V503 at Months 0 and 6

Reporting group description

Boys aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL IM injection at Months 0 and 6. A challenge dose of V503 0.5 mL IM injection was administered at Month 36.

Reporting group title

Girls and Boys 9 to 14 Years V503 at Months 0 and 12

Reporting group description

Girls and boys aged 9 to 14 years received a 2-dose regimen of V503 0.5 mL IM injection at Months 0 and 12. A challenge dose of V503 0.5 mL IM injection was administered at Month 36.

Reporting group title

Girls 9 to 14 Years V503 at Months 0, 2, and 6

Reporting group description

Girls aged 9 to 14 years received a 3-dose regimen of V503 0.5 mL IM injection at Months 0, 2, and 6. A challenge dose of V503 0.5 mL IM injection was administered at Month 36 for a subset of participants.

Reporting group title

Young Women 16 to 26 Years V503 at Months 0, 2, and 6

Reporting group description

Young Women aged 16 to 26 years received a 3-dose regimen of V503 0.5 mL IM injection at Months 0, 2, and 6. A challenge dose of V503 0.5 mL IM injection was administered at Month 36 for a subset of participants.

Serious adverse events	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 294 (2.04%)	9 / 296 (3.04%)	6 / 293 (2.05%)	6 / 300 (2.00%)	11 / 313 (3.51%)
number of deaths (all causes)	0	0	0	1	0
number of deaths resulting from adverse events	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	0 / 293 (0.00%)	1 / 300 (0.33%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Venous thrombosis limb
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	0 / 293 (0.00%)	0 / 300 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Abortion induced
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	0 / 293 (0.00%)	0 / 300 (0.00%)	4 / 313 (1.28%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Premature delivery
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	0 / 293 (0.00%)	0 / 300 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian cyst
subjects affected / exposed	1 / 294 (0.34%)	0 / 296 (0.00%)	0 / 293 (0.00%)	1 / 300 (0.33%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	0 / 293 (0.00%)	1 / 300 (0.33%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Animal bite
subjects affected / exposed	0 / 294 (0.00%)	1 / 296 (0.34%)	0 / 293 (0.00%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 294 (0.00%)	1 / 296 (0.34%)	0 / 293 (0.00%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Forearm fracture
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	1 / 293 (0.34%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Foreign body
subjects affected / exposed	1 / 294 (0.34%)	0 / 296 (0.00%)	0 / 293 (0.00%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal fracture
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	0 / 293 (0.00%)	0 / 300 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac arrest
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	0 / 293 (0.00%)	1 / 300 (0.33%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Wolff-Parkinson-White syndrome
subjects affected / exposed	0 / 294 (0.00%)	1 / 296 (0.34%)	0 / 293 (0.00%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Encephalitis autoimmune
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	0 / 293 (0.00%)	1 / 300 (0.33%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	0 / 294 (0.00%)	1 / 296 (0.34%)	0 / 293 (0.00%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Radiculopathy
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	1 / 293 (0.34%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Status epilepticus
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	0 / 293 (0.00%)	1 / 300 (0.33%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	2 / 294 (0.68%)	0 / 296 (0.00%)	0 / 293 (0.00%)	0 / 300 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 294 (0.00%)	1 / 296 (0.34%)	0 / 293 (0.00%)	0 / 300 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	1 / 293 (0.34%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	0 / 293 (0.00%)	0 / 300 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatitis atopic
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	1 / 293 (0.34%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 294 (0.34%)	1 / 296 (0.34%)	1 / 293 (0.34%)	1 / 300 (0.33%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chikungunya virus infection
subjects affected / exposed	0 / 294 (0.00%)	1 / 296 (0.34%)	0 / 293 (0.00%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dengue fever
subjects affected / exposed	1 / 294 (0.34%)	0 / 296 (0.00%)	0 / 293 (0.00%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	0 / 294 (0.00%)	1 / 296 (0.34%)	0 / 293 (0.00%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis bacterial
subjects affected / exposed	0 / 294 (0.00%)	1 / 296 (0.34%)	0 / 293 (0.00%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oral herpes
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	1 / 293 (0.34%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	1 / 294 (0.34%)	0 / 296 (0.00%)	0 / 293 (0.00%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngotonsillitis
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	0 / 293 (0.00%)	0 / 300 (0.00%)	1 / 313 (0.32%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 294 (0.00%)	1 / 296 (0.34%)	0 / 293 (0.00%)	0 / 300 (0.00%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	0 / 294 (0.00%)	0 / 296 (0.00%)	0 / 293 (0.00%)	1 / 300 (0.33%)	0 / 313 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Girls 9 to 14 Years V503 at Months 0 and 6	Boys 9 to 14 Years V503 at Months 0 and 6	Girls and Boys 9 to 14 Years V503 at Months 0 and 12	Girls 9 to 14 Years V503 at Months 0, 2, and 6	Young Women 16 to 26 Years V503 at Months 0, 2, and 6
Total subjects affected by non serious adverse events
subjects affected / exposed	53 / 294 (18.03%)	32 / 296 (10.81%)	46 / 293 (15.70%)	55 / 300 (18.33%)	90 / 313 (28.75%)
Nervous system disorders
Headache
subjects affected / exposed	8 / 294 (2.72%)	9 / 296 (3.04%)	7 / 293 (2.39%)	7 / 300 (2.33%)	16 / 313 (5.11%)
occurrences all number	9	9	8	8	19
General disorders and administration site conditions
Injection site pain
subjects affected / exposed	49 / 294 (16.67%)	28 / 296 (9.46%)	41 / 293 (13.99%)	53 / 300 (17.67%)	80 / 313 (25.56%)
occurrences all number	65	31	52	81	148

More information

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Were there any global substantial amendments to the protocol? Yes

17 Feb 2015

Amendment 1: Added peripheral blood mononuclear cell (PBMC) collection and testing at Month 24; added U.S. sites and IND number; added participants for PBMC testing.

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Geometric Mean Titers to HPV Type 6 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 6 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 11 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 11 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 16 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 16 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 18 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 18 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 31 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 31 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 33 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 33 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 45 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 45 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 52 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 52 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 58 at Four Weeks After the Last Dose of V503

Primary: Geometric Mean Titers to HPV Type 58 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 6 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 6 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 11 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 11 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 16 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 16 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 18 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 18 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 31 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 31 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 33 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 33 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 45 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 45 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 52 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 52 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 58 at Four Weeks After the Last Dose of V503

Secondary: Percentage of Participants with Seroconversion to HPV Type 58 at Four Weeks After the Last Dose of V503

Other pre-specified: Antibody Persistence: Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 24

Other pre-specified: Antibody Persistence: Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 24

Other pre-specified: Antibody Persistence: Percentage of Participants with Seroconversion to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 24

Other pre-specified: Antibody Persistence: Percentage of Participants with Seroconversion to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 24

Other pre-specified: Antibody Persistence: Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 36

Other pre-specified: Antibody Persistence: Geometric Mean Titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 36

Other pre-specified: Antibody Persistence: Percentage of Participants with Seroconversion to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 36

Other pre-specified: Antibody Persistence: Percentage of Participants with Seroconversion to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 at Month 36

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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