Vaccine To Prevent Cervical Intraepithelial Neoplasia or Cervical Cancer in Younger Healthy Participants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00128661
First received: August 8, 2005
Last updated: May 24, 2012
Last verified: May 2012
Results First Received: December 15, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions: Cervical Cancer
Precancerous Condition
Interventions: Biological: human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine
Biological: hepatitis A inactivated virus vaccine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Solicited symptoms were collected for 3730 and 3740 subjects instead of the 3727 and 3739 subjects who were randomized in the study in the Cervarix and the Havrix groups, respectively. These 4 sujects received both vaccines and were included in the denominator of both arm based on the actual vaccine type administered.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Participant Flow:   Overall Study
    Cervarix Group     Havrix Group  
STARTED     3727     3739  
COMPLETED     3453     3481  
NOT COMPLETED     274     258  
Adverse Event                 14                 11  
Lost to Follow-up                 10                 7  
Withdrawal by Subject                 243                 232  
Unspecified                 7                 8  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Total Total of all reporting groups

Baseline Measures
    Cervarix Group     Havrix Group     Total  
Number of Participants  
[units: participants]
  3727     3739     7466  
Age  
[units: Years]
Mean ± Standard Deviation
     
Years     21.1  ± 2.3     21.1  ± 2.3     21.1  ± 2.3  
Gender  
[units: Subjects]
     
Female     3727     3739     7466  
Male     0     0     0  



  Outcome Measures
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1.  Primary:   Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.   [ Time Frame: From Month 6 up to Month 48 ]

Measure Type Primary
Measure Title Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.
Measure Description

CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer.

Preceding cervical cytology means the last cervical cytology specimen collected before the histopathology specimen was obtained.

Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) by polymerase chain reaction (PCR) at Month 0 and Month 6 for the corresponding HPV-type.

Time Frame From Month 6 up to Month 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2635     2677  
Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.  
[units: Events]
   
HPV16 Associated CIN2+ (N=2464;2452)     1     9  
HPV18 Associated CIN2+ (N=2567; 2593)     0     2  
HPV16 and/or 18 Associated CIN2+ (N=2635;2677)     1     10  

No statistical analysis provided for Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.



2.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: From Month 6 up to Month 48 ]

Measure Type Secondary
Measure Title Number of Cervical Infection With HPV16 or HPV18.
Measure Description Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
Time Frame From Month 6 up to Month 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2635     2677  
Number of Cervical Infection With HPV16 or HPV18.  
[units: Events]
   
HPV16 Cervical Infection (N=2464;2452)     50     251  
HPV18 Cervical Infection (N=2567;2593)     32     177  
HPV16 and/or 18 Cervical Infection (N=2635;2677)     78     387  

No statistical analysis provided for Number of Cervical Infection With HPV16 or HPV18.



3.  Secondary:   Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type   [ Time Frame: From Month 6 up to Month 48 ]

Measure Type Secondary
Measure Title Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type
Measure Description

Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68 detected by polymerase chain reaction (PRC) in the preceding cervical cytology specimen.

Note: The assay did not distinguish between HPV types 68 and 73.

CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer

Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type

Time Frame From Month 6 up to Month 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2643     2697  
Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type  
[units: Events]
   
HPV16 Associated CIN2+ (N=2464;2452)     1     9  
HPV18 Associated CIN2+ (N=2567,2593)     0     2  
HPV31 Associated CIN2+ (N=2525;2546)     1     6  
HPV33 Associated CIN2+ (N=2596;2645)     0     3  
HPV35 Associated CIN2+ (N=2593;2631)     0     4  
HPV39 Associated CIN2+ (N=2528;2581)     0     0  
HPV45 Associated CIN2+ (N=2573;2622)     1     1  
HPV51 Associated CIN2+ (N=2453;2539)     1     6  
HPV52 Associated CIN2+ (N=2456;2505)     5     10  
HPV56 Associated CIN2+ (N=2524;2564)     1     5  
HPV58 Associated CIN2+ (N=2551;2595)     2     5  
HPV59 Associated CIN2+ (N=2576;2637)     3     3  
HPV68 and/or 73 Associated CIN2+ (N=2519;2576)     1     4  
Non 16/18 Onco HPV Associated CIN2+ (N=2643;2697)     11     28  
Any Oncogenic HPV Associated CIN2+ (N=2643;2697)     11     33  

No statistical analysis provided for Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type



4.  Secondary:   Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases   [ Time Frame: From Month 6 up to Month 48 ]

Measure Type Secondary
Measure Title Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases
Measure Description

Persistent incident HPV-16 and /or HPV-18 cervical infection had to fulfil the following criteria: first detection after the 6-month visit, 2 same type HPV positive (by PCR) test results 10+ months apart, and no intervening HPV negative tests for the corresponding type.

Persistent HPV16 or HPV18 cervical infection = detection of the same HPV type by polymerase chain reaction (PCR) in cervical samples from all consecutive evaluations over approximately 12 months.

Subjects were HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type.

Time Frame From Month 6 up to Month 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2635     2677  
Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases  
[units: Events]
   
Persistent HPV16 Infection (N=2464,2452)     10     71  
Persistent HPV18 Infection (N=2567;2593)     0     37  
Persistent HPV16 and/or 18 Infection (N=2635;2677)     10     104  

No statistical analysis provided for Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases



5.  Secondary:   Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.   [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]

Measure Type Secondary
Measure Title Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.
Measure Description

Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Enzyme linked immunosorbent assay (ELISA) and expressed as geometric mean titers (GMTs).

Seronegative subjects = antibody concentration below 8 ELISA Units per millilitre (EL.U/mL) prior to vaccination.

Seropositive subjects=antibody concentration equal to or above 8 EL.U/mL prior to vaccination.

Immunogenicity subcohort = subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7)

Time Frame Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ATP cohort for immunogenicity included subjects who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and during the 48-month follow-up period, who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6) and for whom immunogenicity results were available.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  196     157  
Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.  
[units: Titers]
Geometric Mean ( 95% Confidence Interval )
   
HPV-16 [before vaccination] (N=194;156)     6.7  
  ( 5.7 to 7.8 )  
  8.2  
  ( 6.7 to 10.0 )  
HPV-16 [at Month 1] (N=196,157)     646.6  
  ( 549.3 to 761.1 )  
  7.9  
  ( 6.5 to 9.6 )  
HPV-16 [at Month 6] (N=195,156)     771.5  
  ( 668.3 to 890.7 )  
  8.4  
  ( 6.9 to 10.3 )  
HPV-16 [at Month 7] (N=195,157)     3261  
  ( 2959 to 3595 )  
  8.5  
  ( 6.9 to 10.3 )  
HPV-16 [at Month 12] (N=182,146)     2090  
  ( 1822 to 2398 )  
  8.3  
  ( 6.7 to 10.4 )  
HPV-16 [at Month 18] (N=25,17)     1045  
  ( 776.0 to 1408 )  
  10.4  
  ( 4.8 to 22.7 )  
HPV-16 [at Month 24] (N=175,137)     1486  
  ( 1293 to 1709 )  
  8.6  
  ( 6.9 to 10.7 )  
HPV-16 [at Month 30] (N=19,15)     1070  
  ( 747.5 to 1532 )  
  11.9  
  ( 5.1 to 28.0 )  
HPV-16 [at Month 36] (N=163,132)     1256  
  ( 1080 to 1461 )  
  9.0  
  ( 7.4 to 11.0 )  
HPV-16 [at Month 42] (N=22,18)     1259  
  ( 879.4 to 1802 )  
  6.1  
  ( 4.0 to 9.4 )  
HPV-16 [at Month 48] (N=172,131)     1155  
  ( 1009 to 1322 )  
  9.5  
  ( 7.7 to 11.7 )  

No statistical analysis provided for Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.



6.  Secondary:   Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort   [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]

Measure Type Secondary
Measure Title Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort
Measure Description

Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohortby Enzyme linked immunosorbent assay (ELISA) and expressed as geometric mean titers (GMTs).

Seronegative (Sero-) subjects=antibody concentration below 7 EL.U/mL prior to vaccination.

Seropositive (Sero+) subjects=antibody concentration equal to or above 7 EL.U/mL prior to vaccination.

Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).

Time Frame Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ATP cohort for immunogenicity included subjects who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and during the 48-month follow-up period, who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6) and for whom immunogenicity results were available.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  203     175  
Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort  
[units: Titers]
Geometric Mean ( 95% Confidence Interval )
   
HPV-18 [before vaccination] (N=200;173)     5.4  
  ( 4.8 to 6.1 )  
  6.2  
  ( 5.2 to 7.4 )  
HPV-18 [at Month 1] (N=203;170)     372.7  
  ( 322.8 to 430.3 )  
  6.4  
  ( 5.4 to 7.6 )  
HPV-18 [at Month 6] (N=203;175)     532.2  
  ( 467.5 to 605.9 )  
  6.7  
  ( 5.6 to 7.9 )  
HPV-18 [at Month 7] (N=202;175)     3276  
  ( 3001 to 3576 )  
  6.8  
  ( 5.7 to 8.1 )  
HPV-18 [at Month 12] (N=190;166)     1082  
  ( 942.0 to 1242 )  
  7.0  
  ( 5.7 to 8.5 )  
HPV-18 [at Month 18] (N=28;20)     502.4  
  ( 339.1 to 744.5 )  
  6.7  
  ( 3.8 to 12.1 )  
HPV-18 [at Month 24] (N=178;150)     633.0  
  ( 551.5 to 726.6 )  
  6.9  
  ( 5.6 to 8.4 )  
HPV-18 [at Month 30] (N=17;19)     403.8  
  ( 257.8 to 632.5 )  
  6.4  
  ( 3.8 to 10.5 )  
HPV-18 [at Month 36] (N=168;145)     519.7  
  ( 449.3 to 601.1 )  
  6.0  
  ( 5.0 to 7.2 )  
HPV-18 [at Month 42] (N=25;19)     582.4  
  ( 422.9 to 801.9 )  
  5.5  
  ( 3.6 to 8.4 )  
HPV-18 [at Month 48] (N=179;149)     470.1  
  ( 411.2 to 537.4 )  
  6.6  
  ( 5.5 to 8.0 )  

No statistical analysis provided for Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort



7.  Secondary:   HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)   [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]

Measure Type Secondary
Measure Title HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)
Measure Description

Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Inhibition Enzyme Immunoassay (EIA) and expressed as geometric mean antibody titers (GMTs).

Seronegative (Sero-) subjects=antibody concentration below 41 EL.U/mL prior to vaccination.

Seropositive (Sero+) subjects=antibody concentration equal to or above 41 EL.U/mL prior to vaccination.

Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).

Time Frame Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ATP cohort for immunogenicity included subjects who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and during the 48-month follow-up period, who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6) and for whom immunogenicity results were available.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  196     158  
HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)  
[units: Titers]
Geometric Mean ( 95% Confidence Interval )
   
HPV-16 [before vaccination] (N=196;158)     21.1  
  ( 20.5 to 21.8 )  
  21.4  
  ( 20.6 to 22.3 )  
HPV-16 [at Month 1] (N=182;155)     58.5  
  ( 48.3 to 70.8 )  
  21.5  
  ( 20.7 to 22.3 )  
HPV-16 [at Month 6] (N=189;156)     80.9  
  ( 70.3 to 93.1 )  
  21.5  
  ( 20.6 to 22.4 )  
HPV-16 [at Month 7] (N=193;158)     1047  
  ( 926.3 to 1183 )  
  21.4  
  ( 20.6 to 22.3 )  
HPV-16 [at Month 12] (N=175;146)     291.4  
  ( 253.7 to 334.8 )  
  22.6  
  ( 20.8 to 24.5 )  
HPV-16 [at Month 18] (N=24;17)     116.6  
  ( 83.2 to 163.3 )  
  20.5  
  ( 20.5 to 20.5 )  
HPV-16 [at Month 24] (N=169;138)     184.6  
  ( 163.0 to 209.1 )  
  21.4  
  ( 20.6 to 22.3 )  
HPV-16 [at Month 30] (N=18;15)     112.4  
  ( 78.7 to 160.6 )  
  20.5  
  ( 20.5 to 20.5 )  
HPV-16 [at Month 36] (N=162;132)     139.7  
  ( 122.5 to 159.5 )  
  20.8  
  ( 20.2 to 21.3 )  
HPV-16 [at Month 42] (N=22;18)     126.9  
  ( 89.9 to 179.1 )  
  20.5  
  ( 20.5 to 20.5 )  
HPV-16 [at Month 48] (N=168;133)     131.8  
  ( 115.5 to 150.5 )  
  21.0  
  ( 20.4 to 21.7 )  

No statistical analysis provided for HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)



8.  Secondary:   HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)   [ Time Frame: Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48 ]

Measure Type Secondary
Measure Title HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)
Measure Description

Titers were assessed for the 600 subjects enrolled into the immunogenicity subcohort by Inhibition Enzyme Immunoassay (EIA) and expressed as geometric mean antibody titers (GMTs).

Seronegative (Sero-) subjects=antibody concentration below 110 EL.U/mL prior to vaccination.

Seropositive (Sero+) subjects=antibody concentration equal to or above 110 EL.U/mL prior to vaccination.

Immunogenicity subcohort=subset of 600 subjects from the 2 groups of the ATP cohort: subjects attended 1 extra clinic visit approximately 1 month (30 to 60 days) after the last dose was administered (Month 7).

Time Frame Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The ATP cohort for immunogenicity included subjects who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and during the 48-month follow-up period, who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6) and for whom immunogenicity results were available.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  203     176  
HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)  
[units: Titers]
Geometric Mean ( 95% Confidence Interval )
   
HPV-18 [before vaccination] (N=203;176)     55.0  
  ( 55.0 to 55.0 )  
  55.7  
  ( 54.7 to 56.7 )  
HPV-18 [at Month 1] (N=197;173)     99.1  
  ( 88.0 to 111.5 )  
  55.3  
  ( 54.7 to 55.8 )  
HPV-18 [at Month 6] (N=195;175)     111.4  
  ( 100.2 to 123.9 )  
  55.4  
  ( 54.6 to 56.3 )  
HPV-18 [at Month 7] (N=198;176)     823.6  
  ( 737.7 to 919.5 )  
  55.0  
  ( 55.0 to 55.0 )  
HPV-18 [at Month 12] (N=182;166)     231.1  
  ( 203.2 to 262.7 )  
  56.7  
  ( 54.7 to 58.8 )  
HPV-18 [at Month 18] (N=28;20)     121.8  
  ( 89.5 to 165.8 )  
  55.0  
  ( 55.0 to 55.0 )  
HPV-18 [at Month 24] (N=170;154)     140.8  
  ( 123.8 to 160.2 )  
  55.0  
  ( 55.0 to 55.0 )  
HPV-18 [at Month 30] (N=17;19)     89.5  
  ( 67.6 to 118.7 )  
  55.0  
  ( 55.0 to 55.0 )  
HPV-18 [at Month 36] (N=167;145)     107.9  
  ( 96.0 to 121.2 )  
  55.0  
  ( 55.0 to 55.0 )  
HPV-18 [at Month 42] (N=25;19)     103.3  
  ( 80.3 to 132.9 )  
  55.0  
  ( 55.0 to 55.0 )  
HPV-18 [at Month 48 (N=179;150)     96.9  
  ( 87.7 to 107.0 )  
  56.7  
  ( 54.0 to 59.6 )  

No statistical analysis provided for HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)



9.  Secondary:   Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.   [ Time Frame: Within 60 minutes after vaccination ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.
Measure Description Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).
Time Frame Within 60 minutes after vaccination  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  3730     3740  
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.  
[units: Subjects]
   
Any pain     1627     1610  
Grade 3 pain     25     20  
Any redness     544     501  
Grade 3 redness > 50 mm     0     2  
Any swelling     207     201  
Grade 3 swelling > 50 mm     0     1  

No statistical analysis provided for Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.



10.  Secondary:   Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.   [ Time Frame: Within 60 minutes after vaccination ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.
Measure Description Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and fever (Fever = oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy.Grade 3 urticaria = urticaria distributed on at least 4 body areas. Grade 3 fever = oral temperature > 39.0°C.
Time Frame Within 60 minutes after vaccination  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  3730     3740  
Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.  
[units: Subjects]
   
Any fatigue     512     502  
Grade 3 fatigue     6     5  
Any myalgia     257     232  
Grade 3 myalgia     0     1  
Any arthralgia     58     64  
Grade 3 arthralgia     0     1  
Any gastrointestinal     191     171  
Grade 3 gastrointestinal     0     0  
Any headache     714     718  
Grade 3 headache     2     0  
Any rash     15     17  
Grade 3 rash     0     0  
Any urticaria     19     21  
Grade 3 urticaria     0     0  
Fever (oral) >= 37.5°C     472     477  
Fever (oral) > 39.0°C     0     0  

No statistical analysis provided for Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.



11.  Secondary:   Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.   [ Time Frame: From Day 3 to Day 6 after vaccination ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.
Measure Description Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).
Time Frame From Day 3 to Day 6 after vaccination  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  380     376  
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.  
[units: Subjects]
   
Any pain     202     74  
Grade 3 pain     0     0  
Any redness     6     1  
Grade 3 redness     1     0  
Any swelling     23     1  
Grade 3 swelling     7     0  

No statistical analysis provided for Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.



12.  Secondary:   Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.   [ Time Frame: From Day 3 to Day 6 after vaccination ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.
Measure Description Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and fever (Fever = oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal everyday activities as assessed by inability to attend work or school and which necessitated the administration of corrective therapy.Grade 3 urticaria = urticaria distributed on at least 4 body areas. Grade 3 fever = oral temperature > 39.0°C.
Time Frame From Day 3 to Day 6 after vaccination  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  380     376  
Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.  
[units: Subjects]
   
Any pain     214     189  
Grade 3 pain     2     0  
Any myalgia     250     211  
Grade 3 myalgia     1     0  
Any arthralgia     44     32  
Grade 3 arthralgia     0     0  
Any gastrointestinal     157     119  
Grade 3 gastrointestinal     0     1  
Any headache     247     242  
Grade 3 headache     1     2  
Any rash     31     26  
Grade 3 rash     0     0  
Any urticaria     3     1  
Grade 3 urticaria     0     0  
Fever (oral) >= 37.5°C     43     37  
Fever (oral) > 39.0°C     0     0  

No statistical analysis provided for Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.



13.  Secondary:   Number of Subjects Reporting Serious Adverse Events (SAEs).   [ Time Frame: During the entire study period (From Month 0 up to Month 48). ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Serious Adverse Events (SAEs).
Measure Description SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.
Time Frame During the entire study period (From Month 0 up to Month 48).  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  3727     3739  
Number of Subjects Reporting Serious Adverse Events (SAEs).  
[units: Subjects]
  912     891  

No statistical analysis provided for Number of Subjects Reporting Serious Adverse Events (SAEs).



14.  Secondary:   Number of Subjects Reporting Unsolicited Adverse Events (AEs).   [ Time Frame: During the entire study period (From Month 0 up to Month 48). ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Unsolicited Adverse Events (AEs).
Measure Description An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.
Time Frame During the entire study period (From Month 0 up to Month 48).  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  3727     3739  
Number of Subjects Reporting Unsolicited Adverse Events (AEs).  
[units: Subjects]
  3228     3254  

No statistical analysis provided for Number of Subjects Reporting Unsolicited Adverse Events (AEs).



15.  Secondary:   Number of Subjects With All Possible Pregnancy Outcomes   [ Time Frame: During the entire study period (From Month 0 up to Month 48). ]

Measure Type Secondary
Measure Title Number of Subjects With All Possible Pregnancy Outcomes
Measure Description The range of possible pregnancy outcomes was: Pregnancy loss, Pregnancy resolved alive, and Unresolved pregnancy.
Time Frame During the entire study period (From Month 0 up to Month 48).  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was performed on the Total Vaccinated Cohort, on all pregnant subjects.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2123     2129  
Number of Subjects With All Possible Pregnancy Outcomes  
[units: subjects]
   
Pregnancy loss     317     294  
Pregnancy resolved alive     1756     1766  
Unresolved pregnancy     50     69  

No statistical analysis provided for Number of Subjects With All Possible Pregnancy Outcomes



16.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: During the first year of follow-up period ]

Measure Type Secondary
Measure Title Number of Cervical Infection With HPV16 or HPV18.
Measure Description Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
Time Frame During the first year of follow-up period  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2380     2420  
Number of Cervical Infection With HPV16 or HPV18.  
[units: Events]
   
HPV16 Cervical Infection (N=2242;2232)     21     37  
HPV18 Cervical Infection (N=2330;2347)     7     29  
HPV16 and/or 18 Cervical Infection (N=2380;2420)     27     64  

No statistical analysis provided for Number of Cervical Infection With HPV16 or HPV18.



17.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: During the second year of follow-up period ]

Measure Type Secondary
Measure Title Number of Cervical Infection With HPV16 or HPV18.
Measure Description Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
Time Frame During the second year of follow-up period  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2313     2349  
Number of Cervical Infection With HPV16 or HPV18.  
[units: Events]
   
HPV16 Cervical Infection (N=2170;2176)     10     77  
HPV18 Cervical Infection (N=2269;2307)     9     47  
HPV16 and/or 18 Cervical Infection (N=2313;2349)     18     117  

No statistical analysis provided for Number of Cervical Infection With HPV16 or HPV18.



18.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: During the third year of follow-up period ]

Measure Type Secondary
Measure Title Number of Cervical Infection With HPV16 or HPV18.
Measure Description Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
Time Frame During the third year of follow-up period  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2232     2196  
Number of Cervical Infection With HPV16 or HPV18.  
[units: Events]
   
HPV16 Cervical Infection (N=2097;2026)     6     60  
HPV18 Cervical Infection (N=2200;2196)     6     44  
HPV16 and/or 18 Cervical Infection (N=2236;2166)     11     88  

No statistical analysis provided for Number of Cervical Infection With HPV16 or HPV18.



19.  Secondary:   Number of Cervical Infection With HPV16 or HPV18.   [ Time Frame: From the fourth year follow-up period ]

Measure Type Secondary
Measure Title Number of Cervical Infection With HPV16 or HPV18.
Measure Description Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) (by PCR) at Month 0 and Month 6 for the corresponding HPV-type
Time Frame From the fourth year follow-up period  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The According-To-Protocol (ATP) cohort for efficacy included subjects with efficacy data available, who received 3 doses of vaccine, who were HPV DNA- for the corresponding type at enrollment and at the time of administration of the 3rd dose (Month 6) and who did not have a biopsy or treatment during the vaccination phase (prior to the Month 6).

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  2421     2325  
Number of Cervical Infection With HPV16 or HPV18.  
[units: Events]
   
HPV16 Cervical Infection (N=2277;2139)     13     77  
HPV18 Cervical Infection (N=2389;2325)     10     57  
HPV16 and/or 18 Cervical Infection (N=2421;2261)     22     118  

No statistical analysis provided for Number of Cervical Infection With HPV16 or HPV18.



20.  Secondary:   Number of Subjects Reporting Unsolicited Adverse Events (AEs).   [ Time Frame: within 30 days (Days 0-29) after vaccination ]

Measure Type Secondary
Measure Title Number of Subjects Reporting Unsolicited Adverse Events (AEs).
Measure Description An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.
Time Frame within 30 days (Days 0-29) after vaccination  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Total Vaccinated cohort included all vaccinated subjects with at least 1 vaccine administration documented.

Reporting Groups
  Description
Cervarix Group Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
Havrix Group Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.

Measured Values
    Cervarix Group     Havrix Group  
Number of Participants Analyzed  
[units: participants]
  3727     3739  
Number of Subjects Reporting Unsolicited Adverse Events (AEs).  
[units: Subjects]
  1638     1536  

No statistical analysis provided for Number of Subjects Reporting Unsolicited Adverse Events (AEs).




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The following analysis "occurence of histopathologically confirmed CIN2+ cases associated with HPV16 or HPV18 infection was not performed, in accordance with the Statistical Analysis Plan submitted to the FDA.


  More Information