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Clinical Trial Results:
A Phase IIIb open-label, randomised, multi-centre primary immunization study to evaluate the immunogenicity and safety of GSK Biologicals’ HPV-16/18 L1 VLP AS04 vaccine when administered intramuscularly according to alternative 2-dose schedules in 9 - 14 year old healthy females compared to the standard 3-dose schedule for GSK Biologicals’ HPV-16/18 L1 VLP AS04 vaccine in 15 - 25 year old healthy females

Summary
EudraCT number	2011-000757-22
Trial protocol	DE IT
Global end of trial date	13 Nov 2014

Results information
Results version number	v3(current)
This version publication date	04 Jun 2020
First version publication date	28 May 2015
Other versions	v1 (removed from public view) , v2
Version creation reason

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

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Trial information

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Sponsor protocol code

114700

ISRCTN number

US NCT number

NCT01381575

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

Rue de l’Institut 89, Rixensart, Belgium, B-1330

Public contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.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

07 Aug 2015

Is this the analysis of the primary completion data?

Yes

Primary completion date

28 Jun 2012

Global end of trial reached?

Yes

Global end of trial date

13 Nov 2014

Was the trial ended prematurely?

Main objective of the trial

To demonstrate that the immunogenicity (as determined by [enzyme-linked immunosorbent assay] ELISA) of GSK Biologicals' HPV-16/18 L1 VLP AS04 vaccine administered according to a 2-dose schedule of 0,6 months in 9-14-year old females is non-inferior to that administered according to the standard 3-dose schedule of 0,1,6 months in 15-25-year old females,1 month after the last dose of study vaccine.

Protection of trial subjects

As with all injectable vaccines, appropriate medical treatment was always readily available in case of anaphylactic reactions following the administration of the vaccine. For this reason, the vaccinee remained under medical supervision for 30 minutes after vaccination.

Background therapy

Evidence for comparator

Actual start date of recruitment

29 Jun 2011

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

24 Months

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 190

Country: Number of subjects enrolled

Taiwan: 318

Country: Number of subjects enrolled

Thailand: 314

Country: Number of subjects enrolled

Germany: 325

Country: Number of subjects enrolled

Italy: 300

Worldwide total number of subjects

1447

EEA total number of subjects

625

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)

476

Adolescents (12-17 years)

628

Adults (18-64 years)

343

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This study was conducted by 33 principal investigators in five countries (Canada, Germany, Italy, Taiwan and Thailand).

Screening details

All 1447 subjects enrolled in the study were vaccinated and included in the Total vaccinated cohort (TVC).

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

Cervarix 1 Group

Arm description

Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Day 0 and at Month 6, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

Arm type

Experimental

Investigational medicinal product name

GSK Biologicals' HPV vaccine 580299

Investigational medicinal product code

Other name

Cervarix

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 2 doses of HPV vaccine administered intramuscularly.

Cervarix 2 Group

Arm description

Female subjects aged 15 to 25 years at the time of the first vaccination, who received 3 doses of the Cervarix vaccine at Day 0, at Month 1 and at Month 6, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

Arm type

Active comparator

Investigational medicinal product name

GSK Biologicals' HPV vaccine 580299

Investigational medicinal product code

Other name

Cervarix

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 3 doses of HPV vaccine administered intramuscularly.

Cervarix 3 Group

Arm description

Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Day 0 and at Month 12, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

Arm type

Experimental

Investigational medicinal product name

GSK Biologicals' HPV vaccine 580299

Investigational medicinal product code

Other name

Cervarix

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

Subjects received 2 doses of HPV vaccine administered intramuscularly.

Number of subjects in period 1	Cervarix 1 Group	Cervarix 2 Group	Cervarix 3 Group
Started	550	482	415
Completed	524	443	395
Not completed	26	39	20
Consent withdrawn by subject	15	9	7
Non-Serious Adverse Event	-	-	1
Migrated/moved from study area	2	12	2
Lost to follow-up	8	17	9
Serious Adverse Event	1	-	-
Protocol deviation	-	1	1

Baseline characteristics

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Reporting group title

Cervarix 1 Group

Reporting group description

Reporting group title

Cervarix 2 Group

Reporting group description

Reporting group title

Cervarix 3 Group

Reporting group description

Reporting group values	Cervarix 1 Group	Cervarix 2 Group	Cervarix 3 Group	Total
Number of subjects	550	482	415	1447
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	264	0	212	476
Adolescents (12-17 years)	286	139	203	628
Adults (18-64 years)	0	343	0	343
From 65-84 years	0	0	0	0
85 years and over	0	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	11.6 ( 1.59 )	19.6 ( 3.05 )	11.4 ( 1.55 )	-
Sex: Female, Male
Units: Subjects
Female	550	482	415	1447
Male	0	0	0	0
Race/Ethnicity, Customized
Units: Subjects
African Heritage / African American	6	3	6	15
Asian - Central/South Asian Heritage	1	1	4	6
Asian - East Asian Heritage	141	105	74	320
Asian - South East Asian Heritage	108	106	104	318
White - Arabic / North African Heritage	1	0	1	2
White - Caucasian / European Heritage	288	263	223	774
Mixed origin	5	4	3	12

End points

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Reporting group title

Cervarix 1 Group

Reporting group description

Reporting group title

Cervarix 2 Group

Reporting group description

Reporting group title

Cervarix 3 Group

Reporting group description

Primary: Number of seroconverted subjects for Anti- Human Papilloma virus 16 (Anti-HPV-16) and Anti-Human Papilloma Virus 18 (Anti-HPV-18) antibodies in Cervarix 1 Group and Cervarix 2 Group at Month 7

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End point title

Number of seroconverted subjects for Anti- Human Papilloma virus 16 (Anti-HPV-16) and Anti-Human Papilloma Virus 18 (Anti-HPV-18) antibodies in Cervarix 1 Group and Cervarix 2 Group at Month 7 ^[1]

End point description

Seroconversion was defined as the appearance of antibodies (anti-HPV-16 concentrations greater than or equal to (≥) 8 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL) and anti-HPV-18 concentrations ≥ 7 EL.U/mL) in the serum of subjects seronegative before vaccination. A seronegative subject was a subject with anti-HPV-16/18 antibody concentration lower than (<) 8/7 EL.U/mL, respectively.

End point type

Primary

End point timeframe

At Month 7 (i.e. one month after the last dose of study vaccine)

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 1 Group	Cervarix 2 Group
Number of subjects analysed	493	382
Units: Subjects
Anti-HPV-16 (N=488, 352)	488	352
Anti-HPV-18 (N=493, 382)	493	382

Immune response to anti-HPV-16 in terms of SCR

Statistical analysis description

Immune response to anti-HPV-16 in terms of seroconversion (SCR) rates: To evaluate sequentially if the immunogenicity (as determined by ELISA) of Cervarix vaccine administered according to a 2-dose schedule of 0,6 months in 9-14 year old females was non-inferior to that administered according to the standard 3-dose schedule of 0,1,6 months in 15-25 year old females, 1 month after the last dose of study vaccine, in initially seronegative subjects.

Comparison groups

Cervarix 1 Group v Cervarix 2 Group

Number of subjects included in analysis

875

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

Parameter type

Difference in SCR

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.08

upper limit

0.78

Notes
[2] - Non-inferiority with respect to seroconversion was demonstrated if, 1 month after the last dose, for both anti-HPV-16 and anti-HPV-18, the upper limit of the 95% Confidence Interval (CI) for the difference (Cervarix 2 Group minus Cervarix 1 Group) was below 5%.

Immune response to anti-HPV-18 in terms of SCR

Statistical analysis description

Immune response to anti-HPV-18 in terms of seroconversion (SCR) rates: To evaluate sequentially if the immunogenicity (as determined by ELISA) of Cervarix vaccine administered according to a 2-dose schedule of 0,6 months in 9-14 year old females was non-inferior to that administered according to the standard 3-dose schedule of 0,1,6 months in 15-25 year old females, 1 month after the last dose of study vaccine, in initially seronegative subjects.

Comparison groups

Cervarix 1 Group v Cervarix 2 Group

Number of subjects included in analysis

875

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

Difference in SCR

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1

upper limit

0.77

Notes
[3] - Non-inferiority with respect to seroconversion was demonstrated if, 1 month after the last dose, for both anti-HPV-16 and anti-HPV-18, the upper limit of the 95% Confidence Interval (CI) for the difference (Cervarix 2 Group minus Cervarix 1 Group) was below 5%.

Primary: Anti-HPV-16 and anti-HPV-18 antibody concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Month 7

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End point title

Anti-HPV-16 and anti-HPV-18 antibody concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Month 7 ^[4]

End point description

Antibody concentrations were assessed by ELISA and expressed as geometric mean concentrations (GMCs) in EL.U/mL.

End point type

Primary

End point timeframe

At Month 7 (i.e. one month after the last dose of study vaccine)

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 1 Group	Cervarix 2 Group
Number of subjects analysed	493	382
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-HPV-16 (N=488, 352)	9400.1 (8818.3 to 10020.4)	10234.5 (9258.3 to 11313.6)
Anti-HPV-18 (N=493, 382)	5909.1 (5508.9 to 6338.4)	5002.6 (4572.6 to 5473.1)

Immune response to anti-HPV-16 in terms of GMCs

Statistical analysis description

Immune response to anti-HPV-16 in terms of Geometric Mean Concentrations (GMCs): To evaluate sequentially if the immunogenicity (as determined by ELISA) of Cervarix vaccine administered according to a 2-dose schedule at 0, 6 months in 9-14 year old females was non-inferior to that administered according to the standard 3-dose schedule of 0,1,6 months in 15-25 year old females, 1 month after the last dose of study vaccine, in initially seronegative subjects.

Comparison groups

Cervarix 1 Group v Cervarix 2 Group

Number of subjects included in analysis

875

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

Method

Parameter type

Geometric mean ratio

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.97

upper limit

1.22

Notes
[5] - Non-inferiority with respect to Geometric Mean Concentrations (GMCs) was demonstrated if, 1 month after the last dose, for both anti-HPV-16 and anti-HPV-18, the upper limit of 95% CI for the GMT ratio (Cervarix 2 Group divided by Cervarix 1 Group) was below 2.

Immune response to anti-HPV-18 in terms of GMCs

Statistical analysis description

Immune response to anti-HPV-18 in terms of Geometric Mean Concentrations (GMCs): To evaluate sequentially if the immunogenicity (as determined by ELISA) of Cervarix vaccine administered according to a 2-dose schedule at 0, 6 months in 9-14 year old females was non-inferior to that administered according to the standard 3-dose schedule of 0,1,6 months in 15-25 year old females, 1 month after the last dose of study vaccine, in initially seronegative subjects.

Comparison groups

Cervarix 1 Group v Cervarix 2 Group

Number of subjects included in analysis

875

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

Method

Parameter type

Geometric mean ratio

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.76

upper limit

0.95

Notes
[6] - Non-inferiority with respect to Geometric Mean Concentrations (GMCs) was demonstrated if, 1 month after the last dose, for both anti-HPV-16 and anti-HPV-18, the upper limit of 95% CI for the GMT ratio (Cervarix 2 Group divided by Cervarix 1 Group) was below 2.

Secondary: Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 1 Group and Cervarix 2 Group at Day 0 and at Months 7, 12, 18, 24 and 36

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End point title

Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 1 Group and Cervarix 2 Group at Day 0 and at Months 7, 12, 18, 24 and 36 ^[7]

End point description

Seroconversion was defined as the appearance of antibodies (anti-HPV-16 concentrations ≥ 8 EL.U/mL and anti-HPV-18 concentrations ≥ 7 EL.U/mL [applicable for Day 0, Month 7 and Month 12 time points] and anti-HPV-16 concentrations ≥ 19 EL.U/mL and anti-HPV-18 concentrations ≥ 18 EL.U/mL [applicable for Month 18, Month 24 and Month 36 timepoints]) in the serum of subjects seronegative before vaccination. A seronegative subject was a subject with an anti-HPV-16/18 antibody concentration below (<) the aforementioned cut-offs. Note: In order to increase the ELISA precision, the assay cut-off value was changed from 8 EL.U/mL to 19 EL.U/mL for HPV-16 and from 7 EL.U/mL to 18 EL.U/mL for HPV-18 from Month 18 onwards.

End point type

Secondary

End point timeframe

At Day 0 and at Months 7, 12, 18, 24 and 36

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 1 Group	Cervarix 2 Group
Number of subjects analysed	462	356
Units: Subjects
Anti-HPV-16, Day 0 (N=455, 330)	0	0
Anti-HPV-16, Month 7 (N=455, 330)	455	330
Anti-HPV-16, Month 12 (N=455, 330)	455	330
Anti-HPV-16, Month 18 (N=453, 329)	453	329
Anti-HPV-16, Month 24 (N=454, 326)	454	326
Anti-HPV-16, Month 36 (N=455, 330)	455	330
Anti-HPV-18, Day 0 (N=462, 356)	0	0
Anti-HPV-18, Month 7 (N=462, 356)	462	356
Anti-HPV-18, Month 12 (N=462, 356)	462	356
Anti-HPV-18, Month 18 (N=459, 355)	458	355
Anti-HPV-18, Month 24 (N=460, 352)	459	352
Anti-HPV-18, Month 36 (N=462, 356)	461	355

No statistical analyses for this end point

Secondary: Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Day 0 and at Months 7, 12, 18, 24 and 36

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End point title

Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Day 0 and at Months 7, 12, 18, 24 and 36 ^[8]

End point description

Antibody concentrations were assessed by ELISA and expressed as geometric mean concentrations (GMCs) in EL.U/mL.

End point type

Secondary

End point timeframe

At Day 0 and at Months 7, 12, 18, 24 and 36

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 1 Group	Cervarix 2 Group
Number of subjects analysed	462	356
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-HPV-16, Day 0 (N=455, 330)	4.0 (4.0 to 4.0)	4.0 (4.0 to 4.0)
Anti-HPV-16, Month 7 (N=455, 330)	9402.9 (8792.4 to 10055.8)	10120.2 (9162.7 to 11177.9)
Anti-HPV-16, Month 12 (N=455, 330)	2653.5 (2473.5 to 2846.6)	3290.4 (2956.5 to 3662.0)
Anti-HPV-16, Month 18 (N=453, 329)	1730.7 (1608.6 to 1862.0)	1931.2 (1735.4 to 2149.1)
Anti-HPV-16, Month 24 (N=454, 326)	1483.8 (1382.1 to 1592.9)	1575.9 (1418.2 to 1751.2)
Anti-HPV-16, Month 36 (N=455, 330)	1210.2 (1124.8 to 1302.1)	1326.4 (1193.9 to 1473.5)
Anti-HPV-18, Day 0 (N=462, 356)	3.5 (3.5 to 3.5)	3.5 (3.5 to 3.5)
Anti-HPV-18, Month 7 (N=462, 356)	5935.6 (5519.4 to 6383.3)	4984.2 (4543.9 to 5467.1)
Anti-HPV-18, Month 12 (N=462, 356)	1523.6 (1403.7 to 1653.7)	1491.5 (1339.0 to 1661.4)
Anti-HPV-18, Month 18 (N=459, 355)	864.6 (793.1 to 942.7)	830.6 (742.9 to 928.5)
Anti-HPV-18, Month 24 (N=460, 352)	715.5 (658.1 to 777.9)	654.3 (582.9 to 734.5)
Anti-HPV-18, Month 36 (N=462, 356)	562.8 (516.4 to 613.4)	552.6 (494.1 to 618.0)

No statistical analyses for this end point

Secondary: Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 3 Group

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End point title

Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 3 Group ^[9]

End point description

Seroconversion was defined as the appearance of antibodies (anti-HPV-16 concentrations ≥ 8 EL.U/mL and anti-HPV-18 concentrations ≥ 7 EL.U/mL [applicable for Day 0 and Month 13 time points] and anti-HPV-16 concentrations ≥ 19 EL.U/mL and anti-HPV-18 concentrations ≥ 18 EL.U/mL [applicable for Month 18, Month 24 and Month 36 timepoints]) in the serum of subjects seronegative before vaccination. A seronegative subject was a subject with an anti-HPV-16/18 antibody concentration below (<) the aforementioned cut-offs. Note: In order to increase the ELISA precision, the assay cut-off value was changed from 8 EL.U/mL to 19 EL.U/mL for HPV-16 and from 7 EL.U/mL to 18 EL.U/mL for HPV-18 from Month 18 onwards.

End point type

Secondary

End point timeframe

At Day 0 and at Months 13, 18, 24 and 36

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 3 Group
Number of subjects analysed	355
Units: Subjects
Anti-HPV-16, Day 0 (N=339)	0
Anti-HPV-16, Month 13 (N=339)	339
Anti-HPV-16, Month 18 (N=339)	339
Anti-HPV-16, Month 24 (N=337)	337
Anti-HPV-16, Month 36 (N=339)	339
Anti-HPV-18, Day 0 (N=355)	0
Anti-HPV-18, Month 13 (N=355)	355
Anti-HPV-18, Month 18 (N=355)	355
Anti-HPV-18, Month 24 (N=353)	353
Anti-HPV-18, Month 36 (N=355)	355

No statistical analyses for this end point

Secondary: Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 3 Group

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End point title

Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 3 Group ^[10]

End point description

Antibody concentrations were assessed by ELISA and expressed as geometric mean concentrations (GMCs) in EL.U/mL.

End point type

Secondary

End point timeframe

At Day 0 and at Months 13, 18, 24 and 36

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 3 Group
Number of subjects analysed	355
Units: EL.U/mL
geometric mean (confidence interval 95%)
Anti-HPV-16, Day 0 (N=339)	4.0 (4.0 to 4.0)
Anti-HPV-16, Month 13 (N=339)	11329.4 (10509.3 to 12213.5)
Anti-HPV-16, Month 18 (N=339)	3248.2 (2974.2 to 3547.4)
Anti-HPV-16, Month 24 (N=337)	2191.0 (2003.9 to 2395.5)
Anti-HPV-16, Month 36 (N=339)	1559.3 (1431.2 to 1699.0)
Anti-HPV-18, Day 0 (N=355)	3.5 (3.5 to 3.5)
Anti-HPV-18, Month 13 (N=355)	6580.0 (6075.8 to 7126.0)
Anti-HPV-18, Month 18 (N=355)	1860.3 (1699.4 to 2036.4)
Anti-HPV-18, Month 24 (N=353)	1174.7 (1067.1 to 1293.2)
Anti-HPV-18, Month 36 (N=355)	804.0 (731.8 to 883.4)

No statistical analyses for this end point

Secondary: Anti-HPV-16 and Anti-HPV-18 antibody Titers [by Pseudovirion-Based Neutralisation Assay (PBNA)] in a subset of subjects from Cervarix 3 Group

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End point title

Anti-HPV-16 and Anti-HPV-18 antibody Titers [by Pseudovirion-Based Neutralisation Assay (PBNA)] in a subset of subjects from Cervarix 3 Group ^[11]

End point description

Antibody titers were expressed as geometric mean titers (GMTs). The cut-off of the assay was 40 ED50 for both anti-HPV-16 and anti-HPV-18. The assay was performed on a subset of 100 subjects from Cervarix 3 Group.

End point type

Secondary

End point timeframe

At Day 0 and at Months 13, 18, 24 and 36

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 3 Group
Number of subjects analysed	88
Units: Titers
geometric mean (confidence interval 95%)
Anti-HPV-16, Day 0 (N=88)	20.0 (20.0 to 20.0)
Anti-HPV-16, Month 13 (N=88)	74848.0 (60521.9 to 92565.1)
Anti-HPV-16, Month 18 (N=88)	16576.6 (13127.4 to 20932.0)
Anti-HPV-16, Month 24 (N=87)	10003.7 (8114.1 to 12333.4)
Anti-HPV-16, Month 36 (N=88)	9214.3 (7112.3 to 11937.5)
Anti-HPV-18, Day 0 (N=88)	20.0 (20.0 to 20.0)
Anti-HPV-18, Month 13 (N=88)	39994.7 (33327.2 to 47996.1)
Anti-HPV-18, Month 18 (N=88)	9495.4 (7744.4 to 11642.2)
Anti-HPV-18, Month 24 (N=87)	5464.1 (4377.8 to 6819.8)
Anti-HPV-18, Month 36 (N=88)	4046.4 (3278.0 to 4994.8)

No statistical analyses for this end point

Secondary: Anti-HPV-16 and Anti-HPV-18 Antibody Titers (by PBNA) in a Subset of Subjects From Cervarix 1 Group and Cervarix 2 Group

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End point title

Anti-HPV-16 and Anti-HPV-18 Antibody Titers (by PBNA) in a Subset of Subjects From Cervarix 1 Group and Cervarix 2 Group ^[12]

End point description

Antibody titers were expressed as GMTs. The cut-off of the assay was 40 ED50 for both anti-HPV-16 and anti-HPV-18. The assay was performed on a subset of 100 subjects per study group.

End point type

Secondary

End point timeframe

At Day 0 and Months 7, 12, 18, 24 and 36

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 1 Group	Cervarix 2 Group
Number of subjects analysed	96	92
Units: Titers
geometric mean (confidence interval 95%)
Anti-HPV-16, Day 0 (N=96, 92)	21.3 (18.8 to 24.2)	23.5 (20.7 to 26.6)
Anti-HPV-16, Month 7 (N=96, 92)	82975.9 (67377.4 to 102185.6)	31407.6 (24181.5 to 40793.0)
Anti-HPV-16, Month 12 (N=96, 92)	14872.1 (12025.5 to 18392.4)	15801.8 (12069.8 to 20687.8)
Anti-HPV-16, Month 18 (N=95, 92)	7393.6 (5986.6 to 9131.1)	8246.4 (6224.6 to 10925.0)
Anti-HPV-16, Month 24 (N=96, 92)	6216.5 (5111.0 to 7561.1)	7267.5 (5423.4 to 9738.6)
Anti-HPV-16, Month 36 (N=96, 92)	7762.7 (6218.6 to 9690.1)	5063.7 (3800.4 to 6746.9)
Anti-HPV-18, Day 0 (N=96, 92)	21.0 (19.0 to 23.5)	22.4 (20.4 to 24.5)
Anti-HPV-18, Month 7 (N=96, 92)	24833.1 (20777.0 to 29681.1)	13935.6 (10991.0 to 17669.0)
Anti-HPV-18, Month 12 (N=96, 92)	5914.5 (4756.0 to 7355.4)	5066.5 (3818.9 to 6721.7)
Anti-HPV-18, Month 18 (N=95, 92)	3961.2 (3153.8 to 4975.4)	2958.2 (2213.9 to 3952.6)
Anti-HPV-18, Month 24 (N=96, 92)	2849.4 (2276.0 to 3567.2)	2524.3 (1860.4 to 3425.2)
Anti-HPV-18, Month 36 (N=95, 92)	2416.4 (1905.9 to 3063.5)	1956.2 (1488.5 to 2570.7)

No statistical analyses for this end point

Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific T cell-mediated immune response (CMI) for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

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End point title

Cell-mediated immunogenicity related to anti-HPV-16 specific T cell-mediated immune response (CMI) for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects ^[13]

End point description

The CMI response represents the measure of the cytokines production [i.e. interleukin-2 (IL-2), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α) and the cluster of differentiation 40 Ligand (CD40L)] by HPV-antigen specific T lymphocytes and measured by intracellular cytokine staining (ICS) assay for HPV-16. The frequency was presented as number of cytokine-positive cluster of differentiation (CD)4 i.e. CD4+/CD8+ cells per million CD4+/CD8+ cells. All doubles = T cell expressing at least 2 cytokines. Results were tabulated by the pre-vaccination status of the subjects, where S- = seronegative subjects (antibody concentration < cut-off value) prior to vaccination. S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects per study group.

End point type

Secondary

End point timeframe

At Day 0 and Months 7, 12, 24 and 36

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 1 Group	Cervarix 2 Group
Number of subjects analysed	84	70
Units: cells/million T cells
median (inter-quartile range (Q1-Q3))
Anti-HPV-16, CD4 all doubles, S-, Day 0 (N=81, 68)	88.0 (62.0 to 152.0)	120.0 (67.0 to 185.5)
Anti-HPV-16, CD4 all doubles, S-, Mth 7 (N=69, 50)	3953.0 (1866.0 to 7025.0)	3426.0 (1889.0 to 5214.0)
Anti-HPV-16,CD4 all doubles, S-, Mth 12 (N=84, 70)	2491.0 (1387.5 to 5543.5)	2278.5 (1225.0 to 3363.0)
Anti-HPV-16,CD4 all doubles, S-, Mth 24 (N=78, 67)	2698.0 (1231.0 to 5147.0)	2401 (1231.0 to 3641.0)
Anti-HPV-16,CD4 all doubles, S-, Mth 36 (N=75, 57)	1951.0 (1085.0 to 5130.0)	2073.0 (1012.0 to 2836.0)
Anti-HPV-16, CD4 all doubles, S+, Day 0 (N=8, 14)	77.5 (57.0 to 192.0)	100.0 (60.0 to 269.0)
Anti-HPV-16, CD4 all doubles, S+, Mth 7 (N=8, 13)	5019.5 (1353.0 to 7343.0)	1820.0 (1311.0 to 3021.0)
Anti-HPV-16, CD4 all doubles, S+, Mth 12 (N=9, 14)	2603.0 (1003.0 to 3350.0)	1423.5 (876.0 to 3747.0)
Anti-HPV-16,CD4 all doubles, S+, Mth 24 (N=9, 12)	2552.0 (1156.0 to 3963.0)	1404.0 (1050.0 to 2856.5)
Anti-HPV-16,CD4 all doubles, S+, Mth 36 (N=7, 12)	2180.0 (1293.0 to 3383.0)	1310.0 (939.0 to 2614.5)
Anti-HPV-16, CD4-d-CD40L, S-, Day 0 (N=81, 68)	70.0 (42.0 to 130.0)	97.0 (49.0 to 144.0)
Anti-HPV-16, CD4-d-CD40L, S-, Month 7 (N=69, 50)	3531.0 (1676.0 to 6528.0)	3196.0 (1692.0 to 4771.0)
Anti-HPV-16, CD4-d-CD40L, S-, Month 12 (N=84, 70)	2439.5 (1342.5 to 5376.0)	2255.5 (1185.0 to 3290.0)
Anti-HPV-16, CD4-d-CD40L, S-, Month 24 (N=78, 67)	2443.0 (1111.0 to 4922.0)	2344.0 (1031.0 to 3323.0)
Anti-HPV-16, CD4-d-CD40L, S-, Month 36 (N=75, 57)	1935.0 (1048.0 to 5061.0)	2027.0 (978.0 to 2806.0)
Anti-HPV-16, CD4-d-CD40L, S+, Day 0 (N=8, 14)	57.5 (39.5 to 162.0)	72.5 (40.0 to 186.0)
Anti-HPV-16, CD4-d-CD40L, S+, Month 7 (N=8, 13)	4979.5 (1290.5 to 7001.5)	1655.0 (1050.0 to 2440.0)
Anti-HPV-16, CD4-d-CD40L, S+, Month 12 (N=9, 14)	2587.0 (975.0 to 3305.0)	1412.5 (832.0 to 3677.0)
Anti-HPV-16, CD4-d-CD40L, S+, Month 24 (N=9, 12)	2456.0 (945.0 to 3931.0)	1285.0 (962.5 to 1953.5)
Anti-HPV-16, CD4-d-CD40L, S+, Month 36 (N=7, 12)	2109.0 (1178.0 to 3343.0)	1279.0 (928.0 to 2496.5)
Anti-HPV-16, CD4-d-IFNγ, S-, Day 0 (N=81, 68)	44.0 (19.0 to 67.0)	39.5 (19.5 to 72.0)
Anti-HPV-16, CD4-d-IFNγ, S-, Month 7 (N=69, 50)	840.0 (503.0 to 1538.0)	657.0 (474.0 to 1185.0)
Anti-HPV-16, CD4-d-IFNγ, S-, Month 12 (N=84, 70)	546.0 (176.5 to 1007.5)	362.0 (202.0 to 644.0)
Anti-HPV-16, CD4-d-IFNγ, S-, Month 24 (N=78, 67)	644.5 (294.0 to 1318.0)	449.0 (204.0 to 884.0)
Anti-HPV-16, CD4-d-IFNγ, S-, Month 36 (N=75, 57)	562.0 (273.0 to 1334.0)	391.0 (215.0 to 824.0)
Anti-HPV-16, CD4-d-IFNγ, S+, Day 0 (N=8, 14)	38.5 (26.5 to 86.0)	50.5 (31.0 to 75.0)
Anti-HPV-16, CD4-d-IFNγ, S+, Month 7 (N=8, 13)	881.5 (462.5 to 2704.0)	489.0 (244.0 to 814.0)
Anti-HPV-16, CD4-d-IFNγ, S+, Month 12 (N=9, 14)	533.0 (336.0 to 827.0)	329.0 (183.0 to 481.0)
Anti-HPV-16, CD4-d-IFNγ, S+, Month 24 (N=9, 12)	579.0 (398.0 to 897.0)	310.5 (221.5 to 595.5)
Anti-HPV-16, CD4-d-IFNγ, S+, Month 36 (N=7, 12)	651.0 (520.0 to 998.0)	564.0 (185.5 to 714.5)
Anti-HPV-16, CD4-d-IL-2, S-, Day 0 (N=81, 68)	59.0 (35.0 to 103.0)	85.5 (43.5 to 143.0)
Anti-HPV-16, CD4-d-IL-2, S-, Month 7 (N=69, 50)	3808.0 (1728.0 to 6787.0)	3212.5 (1788.0 to 5010.0)
Anti-HPV-16, CD4-d-IL-2, S-, Month 12 (N=84, 70)	2402.5 (1308.5 to 5242.0)	2184.5 (1156.0 to 3238.0)
Anti-HPV-16, CD4-d-IL-2, S-, Month 24 (N=78, 67)	2477.0 (1140.0 to 4680.0)	2282.0 (1138.0 to 3392.0)
Anti-HPV-16, CD4-d-IL-2, S-, Month 36 (N=75, 57)	1881.0 (958.0 to 4912.0)	1922.0 (892.0 to 2708.0)
Anti-HPV-16, CD4-d-IL-2, S+, Day 0 (N=8, 14)	68.0 (23.0 to 147.5)	77.5 (39.0 to 229.0)
Anti-HPV-16, CD4-d-IL-2, S+, Month 7 (N=8, 13)	4886.0 (1162.5 to 6906.0)	1573.0 (1202.0 to 2924.0)
Anti-HPV-16, CD4-d-IL-2, S+, Month 12 (N=9, 14)	2339.0 (877.0 to 3166.0)	1372.0 (868.0 to 3692.0)
Anti-HPV-16, CD4-d-IL-2, S+, Month 24 (N=9, 12)	2454.0 (1026.0 to 3931.0)	1226.5 (969.0 to 2392.5)
Anti-HPV-16, CD4-d-IL-2, S+, Month 36 (N=7, 12)	2135.0 (1221.0 to 3291.0)	1243.0 (910.5 to 2382.5)
Anti-HPV-16, CD4-d-TNFα, S-, Day 0 (N=81, 68)	59.0 (37.0 to 93.0)	68.0 (29.5 to 110.5)
Anti-HPV-16, CD4-d-TNFα, S-, Month 7 (N=69, 50)	2474.0 (1311.0 to 4800.0)	2575.5 (1224.0 to 3675.0)
Anti-HPV-16, CD4-d-TNFα, S-, Month 12 (N=84, 70)	1944.0 (814.5 to 4150.0)	1726.0 (919.0 to 2481.0)
Anti-HPV-16, CD4-d-TNFα, S-, Month 24 (N=78, 67)	2181.5 (886.0 to 4177.0)	1970.0 (773.0 to 2758.0)
Anti-HPV-16, CD4-d-TNFα, S-, Month 36 (N=75, 57)	1595.0 (700.0 to 3836.0)	1390.0 (672.0 to 2092.0)
Anti-HPV-16, CD4-d-TNFα, S+, Day 0 (N=8, 14)	47.0 (32.0 to 131.0)	64.0 (49.0 to 120.0)
Anti-HPV-16, CD4-d-TNFα, S+, Month 7 (N=8, 13)	2058.5 (1047.0 to 3933.0)	1273.0 (949.0 to 2372.0)
Anti-HPV-16, CD4-d-TNFα, S+, Month 12 (N=9, 14)	1826.0 (875.0 to 2703.0)	1171.0 (733.0 to 2828.0)
Anti-HPV-16, CD4-d-TNFα, S+, Month 24 (N=9, 12)	1851.0 (1039.0 to 2259.0)	1061.5 (878.5 to 2421.5)
Anti-HPV-16, CD4-d-TNFα, S+, Month 36 (N=7, 12)	1138.0 (1031.0 to 2506.0)	1057.0 (732.0 to 2009.0)
Anti-HPV-16, CD8-all doubles, S-, Day 0 (N=81, 68)	11.0 (11.0 to 41.0)	11.0 (11.0 to 44.0)
Anti-HPV-16, CD8-all doubles, S-, Mth 7 (N=69, 50)	11.0 (11.0 to 41.0)	11.0 (11.0 to 36.0)
Anti-HPV-16,CD8 all doubles, S-, Mth 12 (N=84, 70)	30.5 (11.0 to 45.5)	29.5 (11.0 to 50.0)
Anti-HPV-16,CD8-all doubles, S-, Mth 24 (N=78, 67)	11.0 (11.0 to 53.0)	11.0 (11.0 to 54.0)
Anti-HPV-16,CD8-all doubles, S-, Mth 36 (N=75, 57)	37.0 (11.0 to 72.0)	35.0 (11.0 to 59.0)
Anti-HPV-16, CD8-all doubles, S+, Day 0 (N=8, 14)	11.0 (11.0 to 49.0)	35.5 (26.0 to 41.0)
Anti-HPV-16, CD8-all doubles, S+, Mth 7 (N=8, 13)	11.0 (11.0 to 30.5)	33.0 (11.0 to 43.0)
Anti-HPV-16,CD8 all doubles, S+, Mth 12 (N=9, 14)	52.0 (49.0 to 77.0)	29.0 (11.0 to 57.0)
Anti-HPV-16,CD8-all doubles, S+, Mth 24 (N=9, 12)	49.0 (12.0 to 63.0)	11.0 (11.0 to 56.0)
Anti-HPV-16,CD8-all doubles, S+, Mth 36 (N=7, 12)	27.0 (11.0 to 123.0)	11.0 (11.0 to 49.0)
Anti-HPV-16, CD8-d-CD40L, S-, Day 0 (N=81, 68)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-CD40L, S-, Month 7 (N=69, 50)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-CD40L, S-, Month 12 (N=84, 70)	7.0 (7.0 to 32.0)	7.0 (7.0 to 37.0)
Anti-HPV-16, CD8-d-CD40L, S-, Month 24 (N=78, 68)	7.0 (7.0 to 7.0)	7.0 (7.0 to 31.0)
Anti-HPV-16, CD8-d-CD40L, S-, Month 36 (N=75, 57)	11.0 (7.0 to 52.0)	7.0 (7.0 to 32.0)
Anti-HPV-16, CD8-d-CD40L, S+, Day 0 (N=8, 14)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-CD40L, S+, Month 7 (N=8, 13)	7.0 (7.0 to 7.0)	7.0 (7.0 to 22.0)
Anti-HPV-16, CD8-d-CD40L, S+, Month 12 (N=9, 14)	45.0 (7.0 to 48.0)	15.0 (7.0 to 37.0)
Anti-HPV-16, CD8-d-CD40L, S+, Month 24 (N=9, 12)	7.0 (7.0 to 46.0)	7.0 (7.0 to 17.0)
Anti-HPV-16, CD8-d-CD40L, S+, Month 36 (N=7, 12)	7.0 (7.0 to 27.0)	7.0 (7.0 to 15.0)
Anti-HPV-16, CD8-d-IFNγ, S-, Day 0 (N=81, 68)	7.0 (7.0 to 32.0)	7.0 (7.0 to 37.0)
Anti-HPV-16, CD8-d-IFNγ, S-, Month 7 (N=69, 50)	7.0 (7.0 to 35.0)	7.0 (7.0 to 26.0)
Anti-HPV-16, CD8-d-IFNγ, S-, Month 12 (N=84, 70)	7.0 (7.0 to 38.0)	7.0 (7.0 to 46.0)
Anti-HPV-16, CD8-d-IFNγ, S-, Month 24 (N=78, 67)	7.0 (7.0 to 37.0)	7.0 (7.0 to 42.0)
Anti-HPV-16, CD8-d-IFNγ, S-, Month 36 (N=75, 57)	11.0 (7.0 to 44.0)	25.0 (7.0 to 44.0)
Anti-HPV-16, CD8-d-IFNγ, S+, Day 0 (N=8, 14)	7.0 (7.0 to 45.0)	31.5 (22.0 to 37.0)
Anti-HPV-16, CD8-d-IFNγ, S+, Month 7 (N=8, 13)	7.0 (7.0 to 7.0)	22.0 (7.0 to 30.0)
Anti-HPV-16, CD8-d-IFNγ, S+, Month 12 (N=9, 14)	46.0 (31.0 to 54.0)	15.0 (7.0 to 40.0)
Anti-HPV-16, CD8-d-IFNγ, S+, Month 24 (N=9, 12)	8.0 (7.0 to 46.0)	7.0 (7.0 to 23.0)
Anti-HPV-16, CD8-d-IFNγ, S+, Month 36 (N=7, 12)	7.0 (7.0 to 63.0)	7.0 (7.0 to 45.0)
Anti-HPV-16, CD8-d-IL-2, S-, Day 0 (N=81, 68)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-IL-2, S-, Month 7 (N=69, 50)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-IL-2, S-, Month 12 (N=84, 70)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-IL-2, S-, Month 24 (N=78, 67)	7.0 (7.0 to 30.0)	7.0 (7.0 to 30.0)
Anti-HPV-16, CD8-d-IL-2, S-, Month 36 (N=75, 57)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-IL-2, S+, Day 0 (N=8, 14)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-IL-2, S+, Month 7 (N=8, 13)	7.0 (7.0 to 7.0)	7.0 (7.0 to 28.0)
Anti-HPV-16, CD8-d-IL-2, S+, Month 12 (N=9, 14)	7.0 (7.0 to 31.0)	7.0 (7.0 to 23.0)
Anti-HPV-16, CD8-d-IL-2, S+, Month 24 (N=9, 12)	7.0 (7.0 to 45.0)	7.0 (7.0 to 13.0)
Anti-HPV-16, CD8-d-IL-2, S+, Month 36 (N=7, 12)	7 (7.0 to 23.0)	7 (7.0 to 7.0)
Anti-HPV-16, CD8-d-TNFα, S-, Day 0 (N=81, 68)	7.0 (7.0 to 29.0)	7.0 (7.0 to 28.5)
Anti-HPV-16, CD8-d-TNFα, S-, Month 7 (N=69, 50)	7.0 (7.0 to 33.0)	7.0 (7.0 to 32.0)
Anti-HPV-16, CD8-d-TNFα, S-, Month 12 (N=84, 70)	7.0 (7.0 to 38.0)	7.0 (7.0 to 33.0)
Anti-HPV-16, CD8-d-TNFα, S-, Month 24 (N=78, 67)	7.0 (7.0 to 37.0)	7.0 (7.0 to 24.0)
Anti-HPV-16, CD8-d-TNFα, S-, Month 36 (N=75, 57)	7 (7.0 to 36.0)	7 (7.0 to 32.0)
Anti-HPV-16, CD8-d-TNFα, S+, Day 0 (N=8, 14)	7.0 (7.0 to 30.5)	14.5 (7.0 to 31.0)
Anti-HPV-16, CD8-d-TNFα, S+, Month 7 (N=8, 13)	7.0 (7.0 to 26.5)	22.0 (7.0 to 30.0)
Anti-HPV-16, CD8-d-TNFα, S+, Month 12 (N=9, 14)	8.0 (7.0 to 54.0)	23.0 (7.0 to 30.0)
Anti-HPV-16, CD8-d-TNFα, S+, Month 24 (N=9, 12)	8.0 (7.0 to 42.0)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-TNFα, S+, Month 36 (N=7, 12)	7.0 (7.0 to 119.0)	7.0 (7.0 to 7.0)

No statistical analyses for this end point

Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific T CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

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End point title

Cell-mediated immunogenicity related to anti-HPV-18 specific T CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects ^[14]

End point description

The CMI response represents the measure of the cytokines production [IL-2, IFN-γ, TNF-α, and CD40L] by HPV-antigen specific T lymphocytes and measured by ICS assay for HPV-18. The frequency was presented as a number of cytokine-producing CD4+/CD8+ cells per million CD4+/CD8+ cells. All doubles = T cell expressing at least 2 cytokines. Results were tabulated by the pre-vaccination status of the subjects, where S- = seronegative subjects (antibody concentration < the cut-off value) prior to vaccination. S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects per study group.

End point type

Secondary

End point timeframe

At Day 0 and Months 7, 12, 24 and 36

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 1 Group	Cervarix 2 Group
Number of subjects analysed	83	72
Units: cells/million T cells
median (inter-quartile range (Q1-Q3))
Anti-HPV-18, CD4 all doubles, S-, Day 0 (N=77, 69)	86.0 (61.0 to 129.0)	112.0 (75.0 to 177)
Anti-HPV-18, CD4 all doubles, S-,Mth 7 (N=65, 53)	2780.0 (1606.0 to 4289.0)	1864.0 (1158.0 to 2565.0)
Anti-HPV-18,CD4 all doubles, S-,Mth 12 (N=83, 72)	2039.0 (1053.0 to 3481.0)	1246.5 (814.0 to 2045.5)
Anti-HPV-18,CD4 all doubles, S-,Mth 24 (N=76, 68)	1815.5 (877.5 to 3193.0)	1355.0 (638.5 to 2106.0)
Anti-HPV-18,CD4 all doubles, S-,Mth 36 (N= 72, 56)	1609.0 (716.0 to 3322.0)	1246.0 (676.5 to 1751.0)
Anti-HPV-18, CD4 all doubles, S+, Day 0 (N=11, 14)	125.0 (61.0 to 227.0)	128.0 (71.0 to 153.0)
Anti-HPV-18, CD4 all doubles, S+, Mth 7 (N=11, 11)	1593.0 (786.0 to 4012.0)	1498.0 (808.0 to 2727.0)
Anti-HPV-18,CD4 all doubles, S+, Mth 12 (N=10, 13)	868.0 (576.0 to 2069.0)	787.0 (597.0 to 1771.0)
Anti-HPV-18,CD4 all doubles, S+, Mth 24 (N=10, 12)	710.5 (523.0 to 2329.0)	885.0 (475.5 to 2147.5)
Anti-HPV-18,CD4 all doubles, S+, Mth 36 (N=10, 13)	808.5 (624.0 to 1764.0)	598.0 (367.0 to 1414.0)
Anti-HPV-18, CD4-d-CD40L, S-, Day 0 (N=77, 69)	62.0 (35.0 to 105.0)	88.0 (49.0 to 155.0)
Anti-HPV-18, CD4-d-CD40L, S-, Month 7 (N=65, 53)	2634.0 (1331.0 to 3748.0)	1700.0 (993.0 to 2324.0)
Anti-HPV-18, CD4-d-CD40L, S-, Month 12 (N=83, 72)	1967.0 (1019.0 to 3362.0)	1206.5 (797.5 to 2006.0)
Anti-HPV-18, CD4-d-CD40L, S-, Month 24 (N=76, 68)	1632.0 (807.0 to 3133.0)	1290.5 (600.5 to 1911.0)
Anti-HPV-18, CD4-d-CD40L, S-, Month 36 (N=72, 56)	1543.0 (686.0 to 3258.0)	1222.0 (670.0 to 1665.0)
Anti-HPV-18, CD4-d-CD40L, S+, Day 0 (N=11, 14)	121.0 (50.0 to 223.0)	110.5 (44.0 to 142.0)
Anti-HPV-18, CD4-d-CD40L, S+, Month 7 (N=11, 11)	1419.0 (729.0 to 3704.0)	1377.0 (703.0 to 2511.0)
Anti-HPV-18, CD4-d-CD40L, S+, Month 12 (N=10, 13)	830.0 (572.0 to 2008.0)	767.0 (539.0 to 1724.0)
Anti-HPV-18, CD4-d-CD40L, S+, Month 24 (N=10, 12)	652.0 (475.0 to 2151.0)	867.0 (431.0 to 1963.5)
Anti-HPV-18, CD4-d-CD40L, S+, Month 36 (N=10, 13)	794.0 (604.0 to 1721.0)	594.0 (350.0 to 1356.0)
Anti-HPV-18, CD4-d-IFNγ, S-, Day 0 (N=77, 69)	32.0 (19.0 to 55.0)	32.0 (19.0 to 68.0)
Anti-HPV-18, CD4-d-IFNγ, S-, Month 7 (N=65, 53)	562.0 (220.0 to 952.0)	350.0 (192.0 to 554.0)
Anti-HPV-18, CD4-d-IFNγ, S-, Month 12 (N=83, 72)	354.0 (132.0 to 669.0)	216.5 (111.5 to 390.0)
Anti-HPV-18, CD4-d-IFNγ, S-, Month 24 (N=76, 68)	326.5 (166.5 to 799.5)	205.5 (108.5 to 538.0)
Anti-HPV-18, CD4-d-IFNγ, S-, Month 36 (N=72, 56)	304.5 (168.5 to 757.0)	233.5 (114.5 to 485.5)
Anti-HPV-18, CD4-d-IFNγ, S+, Day 0 (N=11, 14)	55.0 (19.0 to 70.0)	28.0 (19.0 to 48.0)
Anti-HPV-18, CD4-d-IFNγ, S+, Month 7 (N=11, 11)	628.0 (186.0 to 1186.0)	376.0 (234.0 to 580.0)
Anti-HPV-18, CD4-d-IFNγ, S+, Month 12 (N=10, 13)	244.5 (120.0 to 535.0)	161.0 (85.0 to 344.0)
Anti-HPV-18, CD4-d-IFNγ, S+, Month 24 (N=10, 12)	295.5 (108.0 to 636.0)	270.5 (94.5 to 455.5)
Anti-HPV-18, CD4-d-IFNγ, S+, Month 36 (N=10, 13)	356.0 (278.0 to 417.0)	239.0 (102.0 to 422.0)
Anti-HPV-18, CD4-d-IL-2, S-, Day 0 (N=77, 69)	57.0 (30.0 to 96.0)	81.0 (36.0 to 127.0)
Anti-HPV-18, CD4-d-IL-2, S-, Month 7 (N=65, 53)	2611.0 (1452.0 to 3953.0)	1725.0 (1026.0 to 2329.0)
Anti-HPV-18, CD4-d-IL-2, S-, Month 12 (N=83, 72)	1959.0 (1009.0 to 3269.0)	1172.5 (755.5 to 1916.0)
Anti-HPV-18, CD4-d-IL-2, S-, Month 24 (N=76, 68)	1638.5 (851.5 to 3084.0)	1306.0 (589.0 to 1977.5)
Anti-HPV-18, CD4-d-IL-2, S-, Month 36 (N=72, 56)	1495.0 (661.0 to 3065.0)	1183.5 (586.5 to 1684.5)
Anti-HPV-18, CD4-d-IL-2, S+, Day 0 (N=11, 14)	65.0 (31.0 to 137.0)	96.5 (48.0 to 102.0)
Anti-HPV-18, CD4-d-IL-2, S+, Month 7 (N=11, 11)	1470.0 (691.0 to 3887.0)	1231.0 (690.0 to 2313.0)
Anti-HPV-18, CD4-d-IL-2, S+, Month 12 (N=10, 13)	847.5 (556.0 to 2022.0)	783.0 (514.0 to 1650.0)
Anti-HPV-18, CD4-d-IL-2, S+, Month 24 (N=10, 12)	652.5 (448.0 to 2269.0)	705.5 (433.0 to 2041.5)
Anti-HPV-18, CD4-d-IL-2, S+, Month 36 (N=10, 13)	777.0 (589.0 to 1669.0)	554.0 (333.0 to 1370.0)
Anti-HPV-18, CD4-d-TNFα, S-, Day 0 (N=77, 69)	49.0 (31.0 to 72.0)	73.0 (27.0 to 138.0)
Anti-HPV-18, CD4-d-TNFα, S-, Month 7 (N=65, 53)	1699.0 (979.0 to 2832.0)	1394.0 (824.0 to 2060.0)
Anti-HPV-18, CD4-d-TNFα, S-, Month 12 (N=83, 72)	1573.0 (715.0 to 2662.0)	991.0 (599.0 to 1617.0)
Anti-HPV-18, CD4-d-TNFα, S-, Month 24 (N=76, 68)	1434.0 (637.5 to 2506.0)	1102.5 (543.0 to 1580.0)
Anti-HPV-18, CD4-d-TNFα, S-, Month 36 (N=72, 56)	1268.0 (473.5 to 2130.0)	868.5 (520.0 to 1296.5)
Anti-HPV-18, CD4-d-TNFα, S+, Day 0 (N=11, 14)	51.0 (44.0 to 159.0)	68.0 (32.0 to 137.0)
Anti-HPV-18, CD4-d-TNFα, S+, Month 7 (N=11, 11)	1337.0 (437.0 to 3141.0)	1137.0 (648.0 to 2211.0)
Anti-HPV-18, CD4-d-TNFα, S+, Month 12 (N=10, 13)	604.0 (391.0 to 1696.0)	684.0 (443.0 to 1284.0)
Anti-HPV-18, CD4-d-TNFα, S+, Month 24 (N=10, 12)	601.0 (462.0 to 2122.0)	768.5 (370.5 to 1673.0)
Anti-HPV-18, CD4-d-TNFα, S+, Month 36 (N=10, 13)	652.5 (489.0 to 1590.0)	444.0 (294.0 to 996.0)
Anti-HPV-18, CD8-all doubles, S-, Day 0 (N=77, 69)	11.0 (11.0 to 36.0)	11.0 (11.0 to 33.0)
Anti-HPV-18, CD8-all doubles, S-, Mth 7 (N=65, 53)	11.0 (11.0 to 37.0)	11.0 (11.0 to 32.0)
Anti-HPV-18,CD8 all doubles, S-, Mth 12 (N=83, 72)	28.0 (11.0 to 47.0)	37.0 (11.0 to 51.5)
Anti-HPV-18,CD8-all doubles, S-, Mth 24 (N=76, 68)	11.0 (11.0 to 51.0)	11.0 (11.0 to 43.0)
Anti-HPV-18,CD8-all doubles, S-, Mth 36 (N=72, 56)	32.0 (11.0 to 45.5)	29.0 (11.0 to 51.0)
Anti-HPV-18, CD8-all doubles, S+, Day 0 (N=11, 14)	11.0 (11.0 to 27.0)	11.0 (11.0 to 34.0)
Anti-HPV-18, CD8-all doubles, S+, Mth 7 (N=11, 11)	11.0 (11.0 to 78.0)	11.0 (11.0 to 73.0)
Anti-HPV-18,CD8 all doubles, S+, Mth 12 (N=10, 13)	44.0 (11.0 to 73.0)	11.0 (11.0 to 33.0)
Anti-HPV-18,CD8-all doubles, S+, Mth 24 (N=10, 12)	19.5 (11.0 to 47.0)	11.0 (11.0 to 36.0)
Anti-HPV-18,CD8-all doubles, S+, Mth 36 (N=10, 13)	45.0 (11.0 to 85.0)	34.0 (11.0 to 50.0)
Anti-HPV-18, CD8-d-CD40L, S-, Day 0 (N=77, 69)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-CD40L, S-, Month 7 (N=65, 53)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-CD40L, S-, Month 12 (N=83, 72)	7.0 (7.0 to 32.0)	7.0 (7.0 to 36.5)
Anti-HPV-18, CD8-d-CD40L, S-, Month 24 (N=76, 68)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-CD40L, S-, Month 36 (N=72, 56)	7.0 (7.0 to 35.5)	7.0 (7.0 to 37.5)
Anti-HPV-18, CD8-d-CD40L, S+, Day 0 (N=11, 14)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-CD40L, S+, Month 7 (N=11, 11)	7.0 (7.0 to 7.0)	7.0 (7.0 to 27.0)
Anti-HPV-18, CD8-d-CD40L, S+, Month 12 (N=10, 13)	34.5 (7.0 to 48.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-CD40L, S+, Month 24 (N=10, 12)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-CD40L, S+, Month 36 (N=10, 13)	25.0 (7.0 to 61.0)	7.0 (7.0 to 30.0)
Anti-HPV-18, CD8-d-IFNγ, S-, Day 0 (N=77, 69)	7.0 (7.0 to 29.0)	7.0 (7.0 to 24.0)
Anti-HPV-18, CD8-d-IFNγ, S-, Month 7 (N=65, 53)	7.0 (7.0 to 26.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IFNγ, S-, Month 12 (N=83, 72)	7.0 (7.0 to 34.0)	7.0 (7.0 to 39.5)
Anti-HPV-18, CD8-d-IFNγ, S-, Month 24 (N=76, 68)	7.0 (7.0 to 29.5)	7.0 (7.0 to 33.5)
Anti-HPV-18, CD8-d-IFNγ, S-, Month 36 (N=72, 56)	7.0 (7.0 to 40.5)	7.0 (7.0 to 34.5)
Anti-HPV-18, CD8-d-IFNγ, S+, Day 0 (N=11, 14)	7.0 (7.0 to 23.0)	7.0 (7.0 to 30.0)
Anti-HPV-18, CD8-d-IFNγ, S+, Month 7 (N=11, 11)	7.0 (7.0 to 74.0)	7.0 (7.0 to 39.0)
Anti-HPV-18, CD8-d-IFNγ, S+, Month 12 (N=10, 13)	16.0 (7.0 to 38.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IFNγ, S+, Month 24 (N=10, 12)	7.0 (7.0 to 9.0)	7.0 (7.0 to 32.0)
Anti-HPV-18, CD8-d-IFNγ, S+, Month 36 (N=10, 13)	7.0 (7.0 to 39.0)	7.0 (7.0 to 40.0)
Anti-HPV-18, CD8-d-IL-2, S-, Day 0 (N=77, 69)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IL-2, S-, Month 7 (N=65, 53)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IL-2, S-, Month 12 (N=83, 72)	7.0 (7.0 to 26.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IL-2, S-, Month 24 (N=76, 68)	7.0 (7.0 to 27.0)	7.0 (7.0 to 14.5)
Anti-HPV-18, CD8-d-IL-2, S-, Month 36 (N=72, 56)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IL-2, S+, Day 0 (N=11, 14)	7.0 (7.0 to 7.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IL-2, S+, Month 7 (N=11, 11)	7.0 (7.0 to 24.0)	7.0 (7.0 to 34.0)
Anti-HPV-18, CD8-d-IL-2, S+, Month 12 (N=10, 13)	7.0 (7.0 to 7.0)	7.0 (7.0 to 23.0)
Anti-HPV-18, CD8-d-IL-2, S+, Month 24 (N=10, 12)	7.0 (7.0 to 24.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IL-2, S+, Month 36 (N=10, 13)	7.0 (7.0 to 39.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-TNFα, S-, Day 0 (N=77, 69)	7.0 (7.0 to 7.0)	7.0 (7.0 to 8.0)
Anti-HPV-18, CD8-d-TNFα, S-, Month 7 (N=65, 53)	7.0 (7.0 to 31.0)	7.0 (7.0 to 27.0)
Anti-HPV-18, CD8-d-TNFα, S-, Month 12 (N=83, 72)	7.0 (7.0 to 31.0)	7.0 (7.0 to 35.0)
Anti-HPV-18, CD8-d-TNFα, S-, Month 24 (N=76, 68)	7.0 (7.0 to 32.5)	7.0 (7.0 to 33.0)
Anti-HPV-18, CD8-d-TNFα, S-, Month 36 (N=72, 56)	7.0 (7.0 to 32.0)	7.0 (7.0 to 35.0)
Anti-HPV-18, CD8-d-TNFα, S+, Day 0 (N=11, 14)	7.0 (7.0 to 23.0)	7.0 (7.0 to 30.0)
Anti-HPV-18, CD8-d-TNFα, S+, Month 7 (N=11, 11)	7.0 (7.0 to 74.0)	7.0 (7.0 to 62.0)
Anti-HPV-18, CD8-d-TNFα, S+, Month 12 (N=10, 13)	7.0 (7.0 to 38.0)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-TNFα, S+, Month 24 (N=10, 12)	7.0 (7.0 to 31.0)	7.0 (7.0 to 16.5)
Anti-HPV-18, CD8-d-TNFα, S+, Month 36 (N=10, 13)	17.0 (7.0 to 57.0)	7.0 (7.0 to 29.0)

No statistical analyses for this end point

Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific T CMI response for Cervarix 3 Group in a sub-cohort of subjects

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End point title

Cell-mediated immunogenicity related to anti-HPV-16 specific T CMI response for Cervarix 3 Group in a sub-cohort of subjects ^[15]

End point description

The CMI response was the measure of the cytokines production (IL-2, IFN-γ, TNF-α, and CD40L) by HPV-antigen specific T lymphocytes and measured by ICS assay for HPV-16. The frequency was presented as a number of cytokine-positive cluster of differentiation (CD)4 i.e.CD4+/CD8+ cells per million CD4+/CD8+ cells. All doubles= T cell expressing at least 2 cytokines. Results were tabulated by the pre-vaccination status of the subjects, where S- = seronegative subjects (antibody concentration < cut-off value) prior to vaccination. S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects from Cervarix 3 Group.

End point type

Secondary

End point timeframe

At Day 0 and at Months 13, 18 and 36

Notes
[15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 3 Group
Number of subjects analysed	77
Units: cells/million T cells
median (inter-quartile range (Q1-Q3))
Anti-HPV-16, CD4 all doubles, S-, Day 0 (N=77)	96.0 (61.0 to 170.0)
Anti-HPV-16, CD4 all doubles, S-, Month 13 (N=73)	2399.0 (1514.0 to 4223.0)
Anti-HPV-16, CD4 all doubles, S-, Month 18 (N=73)	1879.0 (1124.0 to 3449.0)
Anti-HPV-16, CD4 all doubles, S-, Month 36 (N=70)	1786.5 (1064.0 to 3285.0)
Anti-HPV-16, CD4 all doubles, S+, Day 0 (N=7)	169.0 (77.0 to 277.0)
Anti-HPV-16, CD4 all doubles, S+, Month 13 (N=6)	2507.5 (1067.0 to 4212.0)
Anti-HPV-16, CD4 all doubles, S+, Month 18 (N=6)	2717.5 (1597.0 to 4103.0)
Anti-HPV-16, CD4 all doubles, S+, Month 36 (N=7)	1521.0 (297.0 to 3794.0)
Anti-HPV-16, CD4-d-CD40L, S-, Day 0 (N=77)	89.0 (48.0 to 133.0)
Anti-HPV-16, CD4-d-CD40L, S-, Month 13 (N=73)	2356.0 (1510.0 to 4165.0)
Anti-HPV-16, CD4-d-CD40L, S-, Month 18 (N=73)	1831.0 (1070.0 to 3272.0)
Anti-HPV-16, CD4-d-CD40L, S-, Month 36 (N=70)	1763.0 (1048.0 to 3239.0)
Anti-HPV-16, CD4-d-CD40L, S+, Day 0 (N=7)	141.0 (73.0 to 261.0)
Anti-HPV-16, CD4-d-CD40L, S+, Month 13 (N=6)	2450.5 (1036.0 to 4139.0)
Anti-HPV-16, CD4-d-CD40L, S+, Month 18 (N=6)	2614.5 (1580.0 to 3862.0)
Anti-HPV-16, CD4-d-CD40L, S+, Month 36 (N=7)	1426.0 (280.0 to 3697.0)
Anti-HPV-16, CD4-d-IFNγ, S-, Day 0 (N=77)	35.0 (20.0 to 60.0)
Anti-HPV-16, CD4-d-IFNγ, S-, Month 13 (N=73)	651.0 (328.0 to 1356.0)
Anti-HPV-16, CD4-d-IFNγ, S-, Month 18 (N=73)	405.0 (208.0 to 821.0)
Anti-HPV-16, CD4-d-IFNγ, S-, Month 36 (N=70)	646.0 (276.0 to 1282.0)
Anti-HPV-16, CD4-d-IFNγ, S+, Day 0 (N=7)	68.0 (33.0 to 203.0)
Anti-HPV-16, CD4-d-IFNγ, S+, Month 13 (N=6)	644.0 (204.0 to 1163.0)
Anti-HPV-16, CD4-d-IFNγ, S+, Month 18 (N=6)	708.5 (361.0 to 1218.0)
Anti-HPV-16, CD4-d-IFNγ, S+, Month 36 (N=7)	310.0 (72.0 to 1783.0)
Anti-HPV-16, CD4-d-IL-2, S-, Day 0 (N=77)	63.0 (34.0 to 111.0)
Anti-HPV-16, CD4-d-IL-2, S-, Month 13 (N=73)	2220.0 (1406.0 to 4107.0)
Anti-HPV-16, CD4-d-IL-2, S-, Month 18 (N=73)	1830.0 (1084.0 to 3221.0)
Anti-HPV-16, CD4-d-IL-2, S-, Month 36 (N=70)	1670.5 (1009.0 to 3169.0)
Anti-HPV-16, CD4-d-IL-2, S+, Day 0 (N=7)	121.0 (47.0 to 191.0)
Anti-HPV-16, CD4-d-IL-2, S+, Month 13 (N=6)	2442.0 (835.0 to 4006.0)
Anti-HPV-16, CD4-d-IL-2, S+, Month 18 (N=6)	2659.5 (1510.0 to 3870.0)
Anti-HPV-16, CD4-d-IL-2, S+, Month 36 (N=7)	1028.0 (267.0 to 3629.0)
Anti-HPV-16, CD4-d-TNFα, S-, Day 0 (N=77)	63.0 (37.0 to 99.0)
Anti-HPV-16, CD4-d-TNFα, S-, Month 13 (N=73)	1643.0 (907.0 to 2988.0)
Anti-HPV-16, CD4-d-TNFα, S-, Month 18 (N=73)	1326.0 (807.0 to 2627.0)
Anti-HPV-16, CD4-d-TNFα, S-, Month 36 (N=70)	1300.5 (693.0 to 2267.0)
Anti-HPV-16, CD4-d-TNFα, S+, Day 0 (N=7)	140.0 (32.0 to 164.0)
Anti-HPV-16, CD4-d-TNFα, S+, Month 13 (N=6)	1843.0 (584.0 to 2657.0)
Anti-HPV-16, CD4-d-TNFα, S+, Month 18 (N=6)	2085.0 (1380.0 to 2700.0)
Anti-HPV-16, CD4-d-TNFα, S+, Month 36 (N=7)	1202.0 (169.0 to 2745.0)
Anti-HPV-16, CD8-all doubles, S-, Day 0 (N=77)	27.0 (11.0 to 54.0)
Anti-HPV-16, CD8-all doubles, S-, Month 13 (N=73)	11.0 (11.0 to 43.0)
Anti-HPV-16, CD8-all doubles, S-, Month 18 (N=73)	11.0 (11.0 to 53.0)
Anti-HPV-16, CD8-all doubles, S-, Month 36 (N=70)	21.5 (11.0 to 52.0)
Anti-HPV-16, CD8-all doubles, S+, Day 0 (N=7)	33.0 (11.0 to 59.0)
Anti-HPV-16, CD8-all doubles, S+, Month 13 (N=6)	43.0 (11.0 to 57.0)
Anti-HPV-16, CD8-all doubles, S+, Month 18 (N=6)	27.0 (11.0 to 52.0)
Anti-HPV-16, CD8-all doubles, S+, Month 36 (N=7)	11.0 (11.0 to 89.0)
Anti-HPV-16, CD8-d-CD40L, S-, Day 0 (N=77)	7.0 (7.0 to 35.0)
Anti-HPV-16, CD8-d-CD40L, S-, Month 13 (N=73)	7.0 (7.0 to 29.0)
Anti-HPV-16, CD8-d-CD40L, S-, Month 18 (N=73)	7.0 (7.0 to 34.0)
Anti-HPV-16, CD8-d-CD40L, S-, Month 36 (N=70)	7.0 (7.0 to 30.0)
Anti-HPV-16, CD8-d-CD40L, S+, Day 0 (N=7)	7.0 (7.0 to 35.0)
Anti-HPV-16, CD8-d-CD40L, S+, Month 13 (N=6)	7.0 (7.0 to 34.0)
Anti-HPV-16, CD8-d-CD40L, S+, Month 18 (N=6)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-CD40L, S+, Month 36 (N=7)	7.0 (7.0 to 46.0)
Anti-HPV-16, CD8-d-IFNγ, S-, Day 0 (N=77)	7.0 (7.0 to 44.0)
Anti-HPV-16, CD8-d-IFNγ, S-, Month 13 (N=73)	7.0 (7.0 to 35.0)
Anti-HPV-16, CD8-d-IFNγ, S-, Month 18 (N=73)	7.0 (7.0 to 37.0)
Anti-HPV-16, CD8-d-IFNγ, S-, Month 36 (N=70)	7.0 (7.0 to 38.0)
Anti-HPV-16, CD8-d-IFNγ, S+, Day 0 (N=7)	29.0 (7.0 to 55.0)
Anti-HPV-16, CD8-d-IFNγ, S+, Month 13 (N=6)	25.5 (7.0 to 53.0)
Anti-HPV-16, CD8-d-IFNγ, S+, Month 18 (N=6)	7.0 (7.0 to 33.0)
Anti-HPV-16, CD8-d-IFNγ, S+, Month 36 (N=7)	7.0 (7.0 to 46.0)
Anti-HPV-16, CD8-d-IL-2, S-, Day 0 (N=77)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-IL-2, S-, Month 13 (N=73)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-IL-2, S-, Month 18 (N=73)	7.0 (7.0 to 29.0)
Anti-HPV-16, CD8-d-IL-2, S-, Month 36 (N=70)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-IL-2, S+, Day 0 (N=7)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-IL-2, S+, Month 13 (N=6)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-IL-2, S+, Month 18 (N=6)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-IL-2, S+, Month 36 (N=7)	7.0 (7.0 to 46.0)
Anti-HPV-16, CD8-d-TNFα, S-, Day 0 (N=77)	7.0 (7.0 to 27.0)
Anti-HPV-16, CD8-d-TNFα, S-, Month 13 (N=73)	7.0 (7.0 to 29.0)
Anti-HPV-16, CD8-d-TNFα, S-, Month 18 (N=73)	7.0 (7.0 to 41.0)
Anti-HPV-16, CD8-d-TNFα, S-, Month 36 (N=70)	7.0 (7.0 to 38.0)
Anti-HPV-16, CD8-d-TNFα, S+, Day 0 (N=7)	7.0 (7.0 to 7.0)
Anti-HPV-16, CD8-d-TNFα, S+, Month 13 (N=6)	20.5 (7.0 to 44.0)
Anti-HPV-16, CD8-d-TNFα, S+, Month 18 (N=6)	20.0 (7.0 to 39.0)
Anti-HPV-16, CD8-d-TNFα, S+, Month 36 (N=7)	7.0 (7.0 to 7.0)

No statistical analyses for this end point

Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific T CMI response for Cervarix 3 Group in a sub-cohort of subjects

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End point title

Cell-mediated immunogenicity related to anti-HPV-18 specific T CMI response for Cervarix 3 Group in a sub-cohort of subjects ^[16]

End point description

The CMI response was the measure of the cytokines production (IL-2, IFN-γ, TNF-α, and CD40L) by HPV-antigen specific T lymphocytes and measured by ICS assay for HPV-18. The frequency was presented as a number of cytokine-producing CD4+/CD8+ cells per million CD4+/CD8+ cells. All doubles= T cell expressing at least 2 cytokines. Results were tabulated by the pre-vaccination status of the subjects, where S- = seronegative subjects (antibody concentration < cut-off value) prior to vaccination. S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects from Cervarix 3 Group.

End point type

Secondary

End point timeframe

At Day 0 and at Months 13, 18 and 36

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 3 Group
Number of subjects analysed	82
Units: cells/million T-cells
median (inter-quartile range (Q1-Q3))
Anti-HPV-18, CD4 all doubles, S-, Day 0 (N=82)	99.0 (61.0 to 149.0)
Anti-HPV-18, CD4 all doubles, S-, Month 13 (N=77)	1499.0 (1033.0 to 2928.0)
Anti-HPV-18, CD4 all doubles, S-, Month 18 (N=77)	1222.0 (796.0 to 2116.0)
Anti-HPV-18, CD4 all doubles, S-, Month 36 (N=75)	1158.0 (606.0 to 2185.0)
Anti-HPV-18, CD4 all doubles, S+, Day 0 (N=2)	107.5 (69.0 to 146.0)
Anti-HPV-18, CD4 all doubles, S+, Month 13 (N=2)	1968.5 (1753.0 to 2184.0)
Anti-HPV-18, CD4 all doubles, S+, Month 18 (N=2)	1250.0 (1156.0 to 1344.0)
Anti-HPV-18, CD4 all doubles, S+, Month 36 (N=2)	1399.5 (1004.0 to 1795.0)
Anti-HPV-18, CD4-d-CD40L, S-, Day 0 (N=82)	82.5 (42.0 to 125.0)
Anti-HPV-18, CD4-d-CD40L, S-, Month 13 (N=77)	1472.0 (1003.0 to 2880.0)
Anti-HPV-18, CD4-d-CD40L, S-, Month 18 (N=77)	1199.0 (748.0 to 2098.0)
Anti-HPV-18, CD4-d-CD40L, S-, Month 36 (N=75)	1154.0 (563.0 to 2157.0)
Anti-HPV-18, CD4-d-CD40L, S+, Day 0 (N=2)	103.5 (65.0 to 142.0)
Anti-HPV-18, CD4-d-CD40L, S+, Month 13 (N=2)	1904.5 (1656.0 to 2153.0)
Anti-HPV-18, CD4-d-CD40L, S+, Month 18 (N=2)	1174.5 (1110.0 to 1239.0)
Anti-HPV-18, CD4-d-CD40L, S+, Month 36 (N=2)	1320.0 (918.0 to 1722.0)
Anti-HPV-18, CD4-d-IFNγ, S-, Day 0 (N=82)	35.0 (23.0 to 61.0)
Anti-HPV-18, CD4-d-IFNγ, S-, Month 13 (N=77)	349.0 (173.0 to 1221.0)
Anti-HPV-18, CD4-d-IFNγ, S-, Month 18 (N=77)	226.0 (108.0 to 575.0)
Anti-HPV-18, CD4-d-IFNγ, S-, Month 36 (N=75)	318.0 (140.0 to 766.0)
Anti-HPV-18, CD4-d-IFNγ, S+, Day 0 (N=2)	33.5 (24.0 to 43.0)
Anti-HPV-18, CD4-d-IFNγ, S+, Month 13 (N=2)	378.0 (307.0 to 449.0)
Anti-HPV-18, CD4-d-IFNγ, S+, Month 18 (N=2)	157.5 (136.0 to 179.0)
Anti-HPV-18, CD4-d-IFNγ, S+, Month 36 (N=2)	389.0 (231.0 to 547.0)
Anti-HPV-18, CD4-d-IL-2, S-, Day 0 (N=82)	58.5 (32.0 to 98.0)
Anti-HPV-18, CD4-d-IL-2, S-, Month 13 (N=77)	1398.0 (812.0 to 2743.0)
Anti-HPV-18, CD4-d-IL-2, S-, Month 18 (N=77)	1102.0 (719.0 to 1924.0)
Anti-HPV-18, CD4-d-IL-2, S-, Month 36 (N=75)	1086.0 (535.0 to 1974.0)
Anti-HPV-18, CD4-d-IL-2, S+, Day 0 (N=2)	46.5 (33.0 to 60.0)
Anti-HPV-18, CD4-d-IL-2, S+, Month 13 (N=2)	1845.0 (1544.0 to 2146.0)
Anti-HPV-18, CD4-d-IL-2, S+, Month 18 (N=2)	1151.0 (1078.0 to 1224.0)
Anti-HPV-18, CD4-d-IL-2, S+, Month 36 (N=2)	1160.0 (827.0 to 1493.0)
Anti-HPV-18, CD4-d-TNFα, S-, Day 0 (N=82)	60.5 (34.0 to 97.0)
Anti-HPV-18, CD4-d-TNFα, S-, Month 13 (N=77)	1029.0 (649.0 to 2051.0)
Anti-HPV-18, CD4-d-TNFα, S-, Month 18 (N=77)	921.0 (539.0 to 1783.0)
Anti-HPV-18, CD4-d-TNFα, S-, Month 36 (N=75)	812.0 (384.0 to 1545.0)
Anti-HPV-18, CD4-d-TNFα, S+, Day 0 (N=2)	66.5 (29.0 to 104.0)
Anti-HPV-18, CD4-d-TNFα, S+, Month 13 (N=2)	1449.5 (1317.0 to 1582.0)
Anti-HPV-18, CD4-d-TNFα, S+, Month 18 (N=2)	954.5 (873.0 to 1036.0)
Anti-HPV-18, CD4-d-TNFα, S+, Month 36 (N=2)	1127.0 (847.0 to 1407.0)
Anti-HPV-18, CD8-all doubles, S-, Day 0 (N=82)	11.0 (11.0 to 47.0)
Anti-HPV-18, CD8-all doubles, S-, Month 13 (N=77)	32.0 (11.0 to 49.0)
Anti-HPV-18, CD8-all doubles, S-, Month 18 (N=77)	34.0 (11.0 to 50.0)
Anti-HPV-18, CD8-all doubles, S-, Month 36 (N=75)	33.0 (11.0 to 56.0)
Anti-HPV-18, CD8-all doubles, S+, Day 0 (N=2)	29.0 (11.0 to 47.0)
Anti-HPV-18, CD8-all doubles, S+, Month 13 (N=2)	63.5 (39.0 to 88.0)
Anti-HPV-18, CD8-all doubles, S+, Month 18 (N=2)	11.0 (11.0 to 11.0)
Anti-HPV-18, CD8-all doubles, S+, Month 36 (N=2)	45.0 (11.0 to 79.0)
Anti-HPV-18, CD8-d-CD40L, S-, Day 0 (N=82)	7.0 (7.0 to 30.0)
Anti-HPV-18, CD8-d-CD40L, S-, Month 13 (N=77)	7.0 (7.0 to 38.0)
Anti-HPV-18, CD8-d-CD40L, S-, Month 18 (N=77)	7.0 (7.0 to 34.0)
Anti-HPV-18, CD8-d-CD40L, S-, Month 36 (N=75)	7.0 (7.0 to 38.0)
Anti-HPV-18, CD8-d-CD40L, S+, Day 0 (N=82)	25.0 (7.0 to 43.0)
Anti-HPV-18, CD8-d-CD40L, S+, Month 13 (N=2)	21.0 (7.0 to 35.0)
Anti-HPV-18, CD8-d-CD40L, S+, Month 18 (N=2)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-CD40L, S+, Month 36 (N=2)	41.0 (7.0 to 75.0)
Anti-HPV-18, CD8-d-IFNγ, S-, Day 0 (N=82)	7.0 (7.0 to 41.0)
Anti-HPV-18, CD8-d-IFNγ, S-, Month 13 (N=77)	7.0 (7.0 to 40.0)
Anti-HPV-18, CD8-d-IFNγ, S-, Month 18 (N=77)	7.0 (7.0 to 37.0)
Anti-HPV-18, CD8-d-IFNγ, S-, Month 36 (N=75)	7.0 (7.0 to 44.0)
Anti-HPV-18, CD8-d-IFNγ, S+, Day 0 (N=2)	25.0 (7.0 to 43.0)
Anti-HPV-18, CD8-d-IFNγ, S+, Month 13 (N=2)	59.5 (35.0 to 84.0)
Anti-HPV-18, CD8-d-IFNγ, S+, Month 18 (N=2)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IFNγ, S+, Month 36 (N=2)	41.0 (7.0 to 75.0)
Anti-HPV-18, CD8-d-IL-2, S-, Day 0 (N=82)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IL-2, S-, Month 13 (N=77)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IL-2, S-, Month 18 (N=77)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IL-2, S-, Month 36 (N=75)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IL-2, S+, Day 0 (N=2)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IL-2, S+, Month 13 (N=2)	45.5 (7.0 to 84.0)
Anti-HPV-18, CD8-d-IL-2, S+, Month 18 (N=2)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-IL-2, S+, Month 36 (N=2)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-TNFα, S-, Day 0 (N=72)	7.0 (7.0 to 38.0)
Anti-HPV-18, CD8-d-TNFα, S-, Month 13 (N=77)	7.0 (7.0 to 30.0)
Anti-HPV-18, CD8-d-TNFα, S-, Month 18 (N=77)	7.0 (7.0 to 40.0)
Anti-HPV-18, CD8-d-TNFα, S-, Month 36 (N=75)	7.0 (7.0 to 35.0)
Anti-HPV-18, CD8-d-TNFα, S+, Day 0 (N=2)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-TNFα, S+, Month 13 (N=2)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-TNFα, S+, Month 18 (N=2)	7.0 (7.0 to 7.0)
Anti-HPV-18, CD8-d-TNFα, S+, Month 36 (N=2)	7.0 (7.0 to 7.0)

No statistical analyses for this end point

Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific B CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

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End point title

Cell-mediated immunogenicity related to anti-HPV-16 specific B CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects ^[17]

End point description

The CMI response was assessed as being the frequency of B-cell memory of HPV-16 antigen-specific memory B-cells per million memory B-cells in subjects with detectable B-cells. The results are presented by pre-vaccination status, where S- = seronegative subjects (antibody concentration < cut-off value) prior to vaccination and S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects per study group.

End point type

Secondary

End point timeframe

At Day 0 and Months 7, 12, 24 and 36

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 1 Group	Cervarix 2 Group
Number of subjects analysed	75	63
Units: cells/million B-cells
median (inter-quartile range (Q1-Q3))
Anti-HPV-16, S-, Day 0 (N=74, 63)	1.0 (1.0 to 1.0)	1.0 (1.0 to 1.0)
Anti-HPV-16, S-, Month 7 (N=70, 46)	2155.0 (886.0 to 5421.0)	1510.0 (799.0 to 3114.0)
Anti-HPV-16, S-, Month 12 (N=55, 42)	801.0 (361.0 to 2648.0)	1145.0 (371.0 to 3215.0)
Anti-HPV-16, S-, Month 24 (N=75, 60)	318.0 (95.0 to 697.0)	594.5 (147.5 to 1133.5)
Anti-HPV-16, S-, Month 36 (N=70, 53)	560.5 (157.0 to 1012.0)	448.0 (219.0 to 821.0)
Anti-HPV-16, S+, Day 0 (N=8, 13)	1.0 (1.0 to 16.0)	1.0 (1.0 to 51.0)
Anti-HPV-16, S+, Month 7 (N=7, 11)	4838.0 (1513.0 to 11824.0)	477.0 (139.0 to 4928.0)
Anti-HPV-16, S+, Month 12 (N=2, 9)	5056.0 (5018.0 to 5094.0)	539.0 (340.0 to 2111.0)
Anti-HPV-16, S+, Month 24 (N=8, 12)	621.0 (324.5 to 1751.5)	568.5 (50.0 to 1955.0)
Anti-HPV-16, S+, Month 36 (N=6, 13)	475.0 (414.0 to 822.0)	107.0 (1.0 to 1275.0)

No statistical analyses for this end point

Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific B CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

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End point title

Cell-mediated immunogenicity related to anti-HPV-18 specific B CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects ^[18]

End point description

The cell-mediated immune response was assessed as being the frequency of B-cell memory of HPV-18 antigen-specific memory B-cells per million memory B-cells in subjects with detectable B-cells. The results are presented by pre-vaccination status, where S- = seronegative subjects (antibody concentration < cut-off value) prior to vaccination and S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects per study group.

End point type

Secondary

End point timeframe

At Day 0 and at Months 7, 12, 24 and 36

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 1 Group	Cervarix 2 Group
Number of subjects analysed	72	63
Units: cells/million B-cells
median (inter-quartile range (Q1-Q3))
Anti-HPV-18, S-, Day 0 (N=72, 63)	1.0 (1.0 to 1.0)	1.0 (1.0 to 1.0)
Anti-HPV-18, S-, Month 7 (N=67, 48)	958.0 (386.0 to 2500.0)	817.5 (368.0 to 1894.5)
Anti-HPV-18, S-, Month 24 (N=72, 61)	236.0 (61.5 to 710.0)	274.0 (71.0 to 829.0)
Anti-HPV-18, S-, Month 36 (N=67, 54)	269.0 (62.0 to 732.0)	284.5 (90.0 to 582.0)
Anti-HPV-18, S+, Day 0 (N=10, 14)	1.0 (1.0 to 44.0)	1.0 (1.0 to 22.0)
Anti-HPV-18, S+, Month 7 (N=10, 10)	2016.5 (423.0 to 2797.0)	439.5 (31.0 to 1779.0)
Anti-HPV-18, S+, Month 24 (N=11, 12)	299.0 (117.0 to 643.0)	338.5 (174.0 to 786.0)
Anti-HPV-18, S+, Month 36 (N=9, 12)	154.0 (141.0 to 427.0)	93.0 (18.0 to 762.0)

No statistical analyses for this end point

Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific B CMI response for Cervarix 3 Group in a sub-cohort of subjects

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End point title

Cell-mediated immunogenicity related to anti-HPV-16 specific B CMI response for Cervarix 3 Group in a sub-cohort of subjects ^[19]

End point description

The cell-mediated immune response was assessed as being the frequency of B-cell memory of HPV-16 antigen-specific memory B-cells per million memory B-cells in subjects with detectable B-cells. The results are presented by pre-vaccination status, where S- = seronegative subjects (antibody concentration < cut-off value) prior to vaccination and S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects from Cervarix 3 Group.

End point type

Secondary

End point timeframe

At Day 0 and at Months 13, 18 and 36

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 3 Group
Number of subjects analysed	68
Units: cells/million B-cells
median (inter-quartile range (Q1-Q3))
Anti-HPV-16, S-, Day 0 (N=66)	1.0 (1.0 to 7.0)
Anti-HPV-16, S-, Month 13 (N=68)	2809.5 (1402.5 to 5045.5)
Anti-HPV-16, S-, Month 18 (N=60)	766.0 (412.0 to 1946.5)
Anti-HPV-16, S-, Month 36 (N=67)	613.0 (322.0 to 1301.0)
Anti-HPV-16, S+, Day 0 (N=5)	1.0 (1.0 to 20.0)
Anti-HPV-16, S+, Month 13 (N=5)	5996.0 (919.0 to 7353.0)
Anti-HPV-16, S+, Month 18 (N=5)	2130.0 (808.0 to 2271.0)
Anti-HPV-16, S+, Month 36 (N=6)	425.0 (102.0 to 714.0)

No statistical analyses for this end point

Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific B CMI response for Cervarix 3 Group in a sub-cohort of subjects

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End point title

Cell-mediated immunogenicity related to anti-HPV-18 specific B CMI response for Cervarix 3 Group in a sub-cohort of subjects ^[20]

End point description

End point type

Secondary

End point timeframe

At Day 0 and at Months 13, 18 and 36

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.

End point values	Cervarix 3 Group
Number of subjects analysed	72
Units: cells/million B-cells
median (inter-quartile range (Q1-Q3))
Anti-HPV-18, S-, Day 0 (N=70)	1.0 (1.0 to 1.0)
Anti-HPV-18, S-, Month 13 (N=71)	1165.0 (602.0 to 1660.0)
Anti-HPV-18, S-, Month 18 (N=64)	561.5 (132.0 to 1213.5)
Anti-HPV-18, S-, Month 36 (N=72)	361.0 (112.0 to 724.0)
Anti-HPV-18, S+, Day 0 (N=1)	48.0 (48.0 to 48.0)
Anti-HPV-18, S+, Month 13 (N=2)	758.0 (114.0 to 1402.0)
Anti-HPV-18, S+, Month 18 (N=1)	938.0 (938.0 to 938.0)
Anti-HPV-18, S+, Month 36 (N=1)	1231.0 (1231.0 to 1231.0)

No statistical analyses for this end point

Secondary: Number of subjects with any and grade 3 solicited local symptoms

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End point title

Number of subjects with any and grade 3 solicited local symptoms

End point description

Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any solicited local symptom regardless of their intensity grade. Grade 3 pain = significant pain at rest, that prevented normal every day activity. Grade 3 redness/swelling = redness/swelling above 50 millimeters (mm). Subjects from Cervarix 1 and Cervarix 3 Groups received only 2 doses of vaccine, therefore data are presented up to Dose 2.

End point type

Secondary

End point timeframe

During the 7 day period (Days 0-6) after each vaccine dose and across doses

End point values	Cervarix 1 Group	Cervarix 2 Group	Cervarix 3 Group
Number of subjects analysed	550	480	413
Units: Subjects
Any Pain - Dose 1 (N=549, 480, 411)	461	439	354
Grade 3 Pain - Dose 1 (N=549, 480, 411)	24	21	21
Any Pain - Dose 2 (N=544, 470, 404)	446	377	323
Grade 3 Pain - Dose 2 (N=544, 470, 404)	33	25	31
Any Pain - Dose 3 (N=0, 464, 0)	0	358	0
Grade 3 Pain - Dose 3 (N=0, 464, 0)	0	20	0
Any Pain - Across doses (N=550, 480, 413)	499	461	381
Grade 3 Pain - Across doses (N=550, 480, 413)	50	53	48
Any Redness - Dose 1 (N=549, 480, 411)	167	135	126
Grade 3 Redness - Dose 1 (N=549, 480, 411)	0	2	2
Any Redness - Dose 2 (N=544, 470, 404)	180	143	153
Grade 3 Redness - Dose 2 (N=544, 470, 404)	4	5	1
Any Redness - Dose 3 (N=0, 464, 0)	0	142	0
Grade 3 Redness - Dose 3 (N=0, 464, 0)	0	5	0
Any Redness - Across doses (N=550, 480, 413)	247	212	197
Grade 3 Redness - Across doses (N=550, 480, 413)	4	10	3
Any Swelling - Dose 1 (N=549, 480, 411)	141	105	101
Grade 3 Swelling - Dose 1 (N=549, 480, 411)	3	1	4
Any Swelling - Dose 2 (N=544, 470, 404)	166	131	135
Grade 3 Swelling - Dose 2 (N=544, 470, 404)	2	4	2
Any Swelling - Dose 3 (N=0, 464, 0)	0	136	0
Grade 3 Swelling - Dose 3 (N=0, 464, 0)	0	3	0
Any Swelling - Across doses (N=550, 480, 413)	225	204	171
Grade 3 Swelling - Across doses (N=550, 480, 413)	5	6	6

No statistical analyses for this end point

Secondary: Number of subjects with any, grade 3 and related solicited general symptoms

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End point title

Number of subjects with any, grade 3 and related solicited general symptoms

End point description

Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, fever and urticaria. Any = occurrence of any solicited general symptom regardless of intensity grade or relationship to vaccination. Any Fever = axillary temperature ≥ 37.5 degrees Celsius (°C). Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever greater than (>) 39.0 °C. Related = general symptom assessed by the investigator as causally related to the vaccination. Subjects from Cervarix 1 and Cervarix 3 Groups received only 2 doses of vaccine, therefore data are presented up to Dose 2.

End point type

Secondary

End point timeframe

During the 7-day period (Days 0-6) after each vaccine dose and across doses

End point values	Cervarix 1 Group	Cervarix 2 Group	Cervarix 3 Group
Number of subjects analysed	550	480	413
Units: Subjects
Any Artharlgia - Dose 1 (N=549, 480, 411)	61	53	52
Grade 3 Arthralgia - Dose 1 (N=549, 480, 411)	8	3	3
Related Arthralgia - Dose 1 (N=549, 480, 411)	56	50	45
Any Artharlgia - Dose 2 (N=544, 470, 404)	71	56	64
Grade 3 Arthralgia - Dose 2 (N=544, 470, 404)	2	1	3
Related Arthralgia - Dose 2 (N=544, 470, 404)	64	50	57
Any Artharlgia - Dose 3 (N=0, 464, 0)	0	49	0
Grade 3 Arthralgia - Dose 3 (N=0, 464, 0)	0	3	0
Related Arthralgia - Dose 3 (N=0, 464, 0)	0	42	0
Any Artharlgia - Across doses (N=550, 480, 413)	111	107	93
Grade 3 Arthralgia -Across doses (N=550, 480, 413)	9	6	6
Related Arthralgia -Across doses (N=550, 480, 413)	105	102	83
Any Fatigue - Dose 1 (N=549, 480, 411)	181	238	156
Grade 3 Fatigue - Dose 1 (N=549, 480, 411)	7	9	10
Related Fatigue - Dose 1 (N=549, 480, 411)	153	205	129
Any Fatigue - Dose 2 (N=544, 470, 404)	167	168	144
Grade 3 Fatigue - Dose 2 (N=544, 470, 404)	9	11	14
Related Fatigue - Dose 2 (N=544, 470, 404)	149	142	119
Any Fatigue - Dose 3 (N=0, 464, 0)	0	177	0
Grade 3 Fatigue - Dose 3 (N=0, 464, 0)	0	12	0
Related Fatigue - Dose 3 (N=0, 464, 0)	0	161	0
Any Fatigue - Across doses (N=550, 480, 413)	247	310	215
Grade 3 Fatigue - Across doses (N=550, 480, 413)	14	25	21
Related Fatigue - Across doses (N=550, 480, 413)	221	294	185
Any Gastrointestinal - Dose 1 (N=549, 480, 411)	59	88	44
Grade 3 Gastrointestinal -Dose 1 (N=549, 480, 411)	1	2	3
Related Gastrointestinal -Dose 1 (N=549, 480, 411)	49	67	32
Any Gastrointestinal - Dose 2 (N=544, 470, 404)	51	50	48
Grade 3 Gastrointestinal -Dose 2 (N=544, 470, 404)	6	2	4
Related Gastrointestinal -Dose 2 (N=544, 470, 404)	34	36	40
Any Gastrointestinal - Dose 3 (N=0, 464, 0)	0	45	0
Grade 3 Gastrointestinal -Dose 3 (N=0, 464, 0)	0	7	0
Related Gastrointestinal -Dose 3 (N=0, 464, 0)	0	35	0
Any Gastrointestinal -Across doses (N=550,480,413)	98	134	77
Grade 3 Gastroint. -Across doses (N=550, 480, 413)	7	11	7
Related Gastroint. -Across doses (N=550, 480, 413)	77	106	62
Any Headache - Dose 1 (N=549, 480, 411)	133	161	128
Grade 3 Headache - Dose 1 (N=549, 480, 411)	9	10	10
Related Headache - Dose 1 (N=549, 480, 411)	104	136	104
Any Headache - Dose 2 (N=544, 470, 404)	128	129	130
Grade 3 Headache - Dose 2 (N=544, 470, 404)	14	5	6
Related Headache - Dose 2 (N=544, 470, 404)	107	108	100
Any Headache - Dose 3 (N=0, 464, 0)	0	124	0
Grade 3 Headache - Dose 3 (N=0, 464, 0)	0	11	0
Related Headache - Dose 3 (N=0, 464, 0)	0	106	0
Any Headache - Across doses (N=550, 480, 413)	204	246	185
Grade 3 Headache - Across doses (N=550, 480, 413)	19	26	16
Related Headache - Across doses (N=550, 480, 413)	176	219	148
Any Myalgia - Dose 1 (N=549, 480, 411)	206	236	160
Grade 3 Myalgia - Dose 1 (N=549, 480, 411)	16	12	8
Related Myalgia - Dose 1 (N=549, 480, 411)	191	223	140
Any Myalgia - Dose 2 (N=544, 470, 404)	196	182	150
Grade 3 Myalgia - Dose 2 (N=544, 470, 404)	13	11	10
Related Myalgia - Dose 2 (N=544, 470, 404)	182	171	136
Any Myalgia - Dose 3 (N=0, 464, 0)	0	158	0
Grade 3 Myalgia - Dose 3 (N=0, 464, 0)	0	8	0
Related Myalgia - Dose 3 (N=0, 464, 0)	0	150	0
Any Myalgia - Across doses (N=550, 480, 413)	278	295	221
Grade 3 Myalgia - Across doses (N=550, 480, 413)	24	25	15
Related Myalgia - Across doses (N=550, 480, 413)	265	285	201
Any Rash - Dose 1 (N=549, 480, 411)	17	8	15
Grade 3 Rash - Dose 1 (N=549, 480, 411)	1	0	0
Related Rash - Dose 1 (N=549, 480, 411)	13	5	13
Any Rash - Dose 2 (N=544, 470, 404)	17	11	16
Grade 3 Rash - Dose 2 (N=544, 470, 404)	1	0	0
Related Rash - Dose 2 (N=544, 470, 404)	13	10	16
Any Rash - Dose 3 (N=0, 464, 0)	0	8	0
Grade 3 Rash - Dose 3 (N=0, 464, 0)	0	0	0
Related Rash - Dose 3 (N=0, 464, 0)	0	5	0
Any Rash - Across doses (N=550, 480, 413)	33	25	29
Grade 3 Rash - Across doses (N=550, 480, 413)	2	0	0
Related Rash - Across doses (N=550, 480, 413)	26	18	28
Any Fever - Dose 1 (N=549, 480, 411)	24	17	18
Grade 3 Fever - Dose 1 (N=549, 480, 411)	1	0	0
Related Fever - Dose 1 (N=549, 480, 411)	15	12	15
Any Fever - Dose 2 (N=544, 470, 404)	21	15	25
Grade 3 Fever - Dose 2 (N=544, 470, 404)	1	3	1
Related Fever - Dose 2 (N=544, 470, 404)	17	12	18
Any Fever - Dose 3 (N=0, 464, 0)	0	29	0
Grade 3 Fever - Dose 3 (N=0, 464, 0)	0	0	0
Related Fever - Dose 3 (N=0, 464, 0)	0	25	0
Any Fever - Across doses (N=550, 480, 413)	41	48	42
Grade 3 Fever - Across doses (N=550, 480, 413)	2	3	1
Related Fever - Across doses (N=550, 480, 413)	29	39	32
Any Urticaria - Dose 1 (N=549, 480, 411)	9	7	4
Grade 3 Urticaria - Dose 1 (N=549, 480, 411)	1	1	0
Related Urticaria - Dose 1 (N=549, 480, 411)	7	3	4
Any Urticaria - Dose 2 (N=544, 470, 404)	7	9	9
Grade 3 Urticaria - Dose 2 (N=544, 470, 404)	0	0	0
Related Urticaria - Dose 2 (N=544, 470, 404)	6	7	8
Any Urticaria - Dose 3 (N=0, 464, 0)	0	5	0
Grade 3 Urticaria - Dose 3 (N=0, 464, 0)	0	0	0
Related Urticaria - Dose 3 (N=0, 464, 0)	0	3	0
Any Urticaria - Across doses (N=550, 480, 413)	15	15	13
Grade 3 Urticaria - Across doses (N=550, 480, 413)	1	1	0
Related Urticaria - Across doses (N=550, 480, 413)	13	11	12

No statistical analyses for this end point

Secondary: Number of subjects with any, grade 3 and related unsolicited adverse events (AEs)

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End point title

Number of subjects with any, grade 3 and related unsolicited adverse events (AEs)

End point description

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any = any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 = unsolicited AE preventing normal activity. Related = unsolicited AE assessed by the investigator as causally related to the study vaccination.

End point type

Secondary

End point timeframe

During the 30-day (Days 0-29) post-vaccination period

End point values	Cervarix 1 Group	Cervarix 2 Group	Cervarix 3 Group
Number of subjects analysed	550	482	415
Units: Subjects
Any unsolicited AEs	97	167	74
Grade 3 unsolicited AEs	2	17	6
Related unsolicited AEs	11	24	13

No statistical analyses for this end point

Secondary: Number of subjects with any potential Immune-Mediated Diseases (pIMDs)

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End point title

Number of subjects with any potential Immune-Mediated Diseases (pIMDs)

End point description

pIMDs are a subset of AEs that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. The data for Cervarix 1 and 2 Groups are only presented up to Month 13, as the data were only collected up to Month 13 for those 2 groups.

End point type

Secondary

End point timeframe

From Day 0 up to Month 13 (for Cervarix 1 Group and Cervarix 2 Group) and from Day 0 up to Month 18 (for Cervarix 3 Group)

End point values	Cervarix 1 Group	Cervarix 2 Group	Cervarix 3 Group
Number of subjects analysed	550	482	415
Units: Subjects
Any pIMDs,from Day 0 up to Month 13(N=550,482,415)	2	2	2
Any pIMDs, from Day 0 up to Month 18 (N=0, 0, 415)	0	0	2

No statistical analyses for this end point

Secondary: Number of subjects with Medically Significant Conditions (MSCs)

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End point title

Number of subjects with Medically Significant Conditions (MSCs)

End point description

MSC include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.

End point type

Secondary

End point timeframe

From Day 0 up to Month 36 (throughout the study period)

End point values	Cervarix 1 Group	Cervarix 2 Group	Cervarix 3 Group
Number of subjects analysed	550	482	415
Units: Subjects	134	153	87

No statistical analyses for this end point

Secondary: Number of subjects with any, related and fatal serious adverse events (SAEs)

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End point title

Number of subjects with any, related and fatal serious adverse events (SAEs)

End point description

SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject. Any = any SAE regardless of intensity grade or relation to vaccination. Related = SAE assessed by the investigator as causally related to the study vaccination.

End point type

Secondary

End point timeframe

From Day 0 up to Month 36 (throughout the study period)

End point values	Cervarix 1 Group	Cervarix 2 Group	Cervarix 3 Group
Number of subjects analysed	550	482	415
Units: Subjects
Any SAEs	20	28	24
Related SAEs	0	0	1
Fatal SAEs	0	0	0

No statistical analyses for this end point

Secondary: Number of subjects reporting pregnancies and outcomes of reported pregnancies

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End point title

Number of subjects reporting pregnancies and outcomes of reported pregnancies

End point description

Outcomes of reported pregnancies were: Ectopic pregnancy, Elective termination NO apparent congenital anomaly (ACA), Live Infant NO ACA, Stillbirth NO ACA.

End point type

Secondary

End point timeframe

From Day 0 up to Month 36 (throughout the study period)

End point values	Cervarix 1 Group	Cervarix 2 Group	Cervarix 3 Group
Number of subjects analysed	1	34	1
Units: Subjects
Ectopic pregnancy	0	1	0
Elective termination NO ACA	0	2	0
Live Infant NO ACA	1	30	1
Stillbirth NO ACA	0	1	0

No statistical analyses for this end point

Secondary: Number of subjects completing the vaccination course

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End point title

Number of subjects completing the vaccination course

End point description

The number of subjects completing the vaccination course was assessed as the number of subjects with at least one dose received during the study.

End point type

Secondary

End point timeframe

From Day 0 up to Month 13

End point values	Cervarix 1 Group	Cervarix 2 Group	Cervarix 3 Group
Number of subjects analysed	550	482	415
Units: Subjects	550	482	415

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited symptoms were collected during the 7-day period (Days 0-6) after vaccination. Unsolicited AEs were collected during the 30-day period (Days 0-29) after vaccination. SAEs were collected from Day 0 to Month 36.

Adverse event reporting additional description

The occurrence of reported AEs (all/related) was not available and encoded as equal to the number of subjects affected. For the systematically assessed other (non-serious) adverse events, the number of exposed subjects included those from Total Vaccinated cohort who had the symptom sheet completed.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

Cervarix 1 Group

Reporting group description

Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Months 0 and 6. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

Reporting group title

Cervarix 2 Group

Reporting group description

Female subjects aged 15 to 25 years at the time of the first vaccination, who received 3 doses of the Cervarix vaccine at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

Reporting group title

Cervarix 3 Group

Reporting group description

Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Months 0 and 12. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

Serious adverse events	Cervarix 1 Group	Cervarix 2 Group	Cervarix 3 Group
Total subjects affected by serious adverse events
subjects affected / exposed	20 / 550 (3.64%)	28 / 482 (5.81%)	24 / 415 (5.78%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Medulloblastoma
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholesteatoma
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Synovial sarcoma
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Uterine leiomyoma
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Circulatory collapse
subjects affected / exposed	0 / 550 (0.00%)	0 / 482 (0.00%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Ectopic pregnancy termination
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Hyperemesis gravidarum
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Premature baby
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abortion threatened
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Postpartum haemorrhage
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Stillbirth
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	0 / 550 (0.00%)	0 / 482 (0.00%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anaphylactic reaction
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian cyst ruptured
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Transient tachypnoea of the newborn
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory disorder
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tonsillar hypertrophy
subjects affected / exposed	0 / 550 (0.00%)	0 / 482 (0.00%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Psychotic disorder
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Schizoaffective disorder
subjects affected / exposed	0 / 550 (0.00%)	2 / 482 (0.41%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Foot fracture
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Forearm fracture
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Carbon monoxide poisoning
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intentional overdose
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ligament rupture
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Traumatic intracranial haemorrhage
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Alcohol poisoning
subjects affected / exposed	0 / 550 (0.00%)	0 / 482 (0.00%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Supraventricular tachycardia
subjects affected / exposed	0 / 550 (0.00%)	0 / 482 (0.00%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Seizure
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VIIth nerve paralysis
subjects affected / exposed	0 / 550 (0.00%)	0 / 482 (0.00%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphadenitis
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Strabismus
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal strangulated hernia
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal pain lower
subjects affected / exposed	0 / 550 (0.00%)	0 / 482 (0.00%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Anal haemorrhage
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 550 (0.00%)	0 / 482 (0.00%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dyspepsia
subjects affected / exposed	0 / 550 (0.00%)	0 / 482 (0.00%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Faecaloma
subjects affected / exposed	0 / 550 (0.00%)	0 / 482 (0.00%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic gastritis
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
IgA nephropathy
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocrine disorders
Autoimmune thyroiditis
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Synovial cyst
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Systemic lupus erythematosus
subjects affected / exposed	0 / 550 (0.00%)	0 / 482 (0.00%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Dengue fever
subjects affected / exposed	1 / 550 (0.18%)	4 / 482 (0.83%)	3 / 415 (0.72%)
occurrences causally related to treatment / all	0 / 1	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis bacterial
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	1 / 550 (0.18%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tubo-ovarian abscess
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	1 / 550 (0.18%)	1 / 482 (0.21%)	2 / 415 (0.48%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Otitis media chronic
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infectious mononucleosis
subjects affected / exposed	0 / 550 (0.00%)	0 / 482 (0.00%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pelvic inflammatory disease
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Salpingitis
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Salpingo-oophoritis
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Otitis media acute
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pelvic infection
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 550 (0.00%)	0 / 482 (0.00%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 550 (0.00%)	3 / 482 (0.62%)	5 / 415 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	2 / 550 (0.36%)	1 / 482 (0.21%)	2 / 415 (0.48%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypovolaemia
subjects affected / exposed	0 / 550 (0.00%)	1 / 482 (0.21%)	1 / 415 (0.24%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Type 1 diabetes mellitus
subjects affected / exposed	1 / 550 (0.18%)	0 / 482 (0.00%)	0 / 415 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Cervarix 1 Group	Cervarix 2 Group	Cervarix 3 Group
Total subjects affected by non serious adverse events
subjects affected / exposed	513 / 550 (93.27%)	466 / 482 (96.68%)	387 / 415 (93.25%)
General disorders and administration site conditions
Pain
subjects affected / exposed ^[1]	499 / 550 (90.73%)	461 / 480 (96.04%)	381 / 413 (92.25%)
occurrences all number	499	461	381
Redness
subjects affected / exposed ^[2]	247 / 550 (44.91%)	212 / 480 (44.17%)	197 / 413 (47.70%)
occurrences all number	247	212	197
Swelling
subjects affected / exposed ^[3]	225 / 550 (40.91%)	204 / 480 (42.50%)	171 / 413 (41.40%)
occurrences all number	225	204	171
Arthralgia
subjects affected / exposed ^[4]	111 / 550 (20.18%)	107 / 480 (22.29%)	93 / 413 (22.52%)
occurrences all number	111	107	93
Fatigue
subjects affected / exposed ^[5]	247 / 550 (44.91%)	310 / 480 (64.58%)	215 / 413 (52.06%)
occurrences all number	247	310	215
Gastrointestinal symptoms
subjects affected / exposed ^[6]	98 / 550 (17.82%)	134 / 480 (27.92%)	77 / 413 (18.64%)
occurrences all number	98	134	77
Headache
subjects affected / exposed ^[7]	204 / 550 (37.09%)	246 / 480 (51.25%)	185 / 413 (44.79%)
occurrences all number	204	246	185
Myalgia
subjects affected / exposed ^[8]	278 / 550 (50.55%)	295 / 480 (61.46%)	221 / 413 (53.51%)
occurrences all number	278	295	221
Rash
subjects affected / exposed ^[9]	33 / 550 (6.00%)	25 / 480 (5.21%)	29 / 413 (7.02%)
occurrences all number	33	25	29
Fever
subjects affected / exposed ^[10]	41 / 550 (7.45%)	48 / 480 (10.00%)	42 / 413 (10.17%)
occurrences all number	41	48	42
Infections and infestations
Nasopharyngitis
subjects affected / exposed	22 / 550 (4.00%)	27 / 482 (5.60%)	14 / 415 (3.37%)
occurrences all number	22	27	14

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.

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Were there any global substantial amendments to the protocol? Yes

26 Nov 2013

The HPV-070 protocol is being amended for the following reason: The assay used to measure anti-HPV-16/-18 antibody concentrations at the designated laboratory was improved to increase the assay precision by changing the assay cut-off value from 8 EL.U/mL to 19 EL.U/mL for HPV-16 and from 7 EL.U/mL to 18 EL.U/mL for HPV-18. This change in the assay was implemented for the testing of samples from Month 18 onwards.

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: Number of seroconverted subjects for Anti- Human Papilloma virus 16 (Anti-HPV-16) and Anti-Human Papilloma Virus 18 (Anti-HPV-18) antibodies in Cervarix 1 Group and Cervarix 2 Group at Month 7

Primary: Number of seroconverted subjects for Anti- Human Papilloma virus 16 (Anti-HPV-16) and Anti-Human Papilloma Virus 18 (Anti-HPV-18) antibodies in Cervarix 1 Group and Cervarix 2 Group at Month 7

Primary: Anti-HPV-16 and anti-HPV-18 antibody concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Month 7

Primary: Anti-HPV-16 and anti-HPV-18 antibody concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Month 7

Secondary: Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 1 Group and Cervarix 2 Group at Day 0 and at Months 7, 12, 18, 24 and 36

Secondary: Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 1 Group and Cervarix 2 Group at Day 0 and at Months 7, 12, 18, 24 and 36

Secondary: Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Day 0 and at Months 7, 12, 18, 24 and 36

Secondary: Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Day 0 and at Months 7, 12, 18, 24 and 36

Secondary: Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 3 Group

Secondary: Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 3 Group

Secondary: Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 3 Group

Secondary: Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 3 Group

Secondary: Anti-HPV-16 and Anti-HPV-18 antibody Titers [by Pseudovirion-Based Neutralisation Assay (PBNA)] in a subset of subjects from Cervarix 3 Group

Secondary: Anti-HPV-16 and Anti-HPV-18 antibody Titers [by Pseudovirion-Based Neutralisation Assay (PBNA)] in a subset of subjects from Cervarix 3 Group

Secondary: Anti-HPV-16 and Anti-HPV-18 Antibody Titers (by PBNA) in a Subset of Subjects From Cervarix 1 Group and Cervarix 2 Group

Secondary: Anti-HPV-16 and Anti-HPV-18 Antibody Titers (by PBNA) in a Subset of Subjects From Cervarix 1 Group and Cervarix 2 Group

Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific T cell-mediated immune response (CMI) for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific T cell-mediated immune response (CMI) for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific T CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific T CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific T CMI response for Cervarix 3 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific T CMI response for Cervarix 3 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific T CMI response for Cervarix 3 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific T CMI response for Cervarix 3 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific B CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific B CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific B CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific B CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific B CMI response for Cervarix 3 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific B CMI response for Cervarix 3 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific B CMI response for Cervarix 3 Group in a sub-cohort of subjects

Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific B CMI response for Cervarix 3 Group in a sub-cohort of subjects

Secondary: Number of subjects with any and grade 3 solicited local symptoms

Secondary: Number of subjects with any and grade 3 solicited local symptoms

Secondary: Number of subjects with any, grade 3 and related solicited general symptoms

Secondary: Number of subjects with any, grade 3 and related solicited general symptoms

Secondary: Number of subjects with any, grade 3 and related unsolicited adverse events (AEs)

Secondary: Number of subjects with any, grade 3 and related unsolicited adverse events (AEs)

Secondary: Number of subjects with any potential Immune-Mediated Diseases (pIMDs)

Secondary: Number of subjects with any potential Immune-Mediated Diseases (pIMDs)

Secondary: Number of subjects with Medically Significant Conditions (MSCs)

Secondary: Number of subjects with Medically Significant Conditions (MSCs)

Secondary: Number of subjects with any, related and fatal serious adverse events (SAEs)

Secondary: Number of subjects with any, related and fatal serious adverse events (SAEs)

Secondary: Number of subjects reporting pregnancies and outcomes of reported pregnancies

Secondary: Number of subjects reporting pregnancies and outcomes of reported pregnancies

Secondary: Number of subjects completing the vaccination course

Secondary: Number of subjects completing the vaccination course

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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