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Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' Human Papillomavirus (HPV) Vaccine (GSK-580299) and Merck's Gardasil Vaccine When Administered According to Alternative 2-dose Schedules in 9-14 Year Old Females

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT01462357
Collaborator
(none)
1,079
Enrollment
21
Locations
3
Arms
47.2
Actual Duration (Months)
51.4
Patients Per Site
1.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the immunogenicity and the safety of Cervarix administered according to a 2-dose schedule at 0, 6 months compared to Gardasil, administered according to a 2-dose schedule at 0, 6 months or the standard 3-dose schedule of 0, 2, 6 months in 9-14 years old healthy females.

Condition or Disease Intervention/Treatment Phase
  • Biological: Cervarix
  • Biological: Gardasil
  • Drug: Placebo
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1079 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' HPV-16/18 L1 AS04 Vaccine and Merck's Gardasil Vaccine When Administered According to Alternative 2-dose Schedules in 9-14 Year Old Females
Actual Study Start Date :
Nov 21, 2011
Actual Primary Completion Date :
Oct 27, 2015
Actual Study Completion Date :
Oct 27, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cervarix 2 dose Group

Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.

Biological: Cervarix
2 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Day 0 and Month 6.

Drug: Placebo
2 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 2 to maintain blinding.
Experimental: Gardasil 2 dose Group

Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.

Biological: Gardasil
2 or 3 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes or vials to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Day 0 and Month 6 (Gardasil 2 dose Group) or at Day 0, Month 2 and Month 6 (Gardasil 3 dose Group), respectively.

Drug: Placebo
2 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 2 to maintain blinding.
Experimental: Gardasil 3 dose Group

Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.

Biological: Gardasil
2 or 3 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes or vials to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Day 0 and Month 6 (Gardasil 2 dose Group) or at Day 0, Month 2 and Month 6 (Gardasil 3 dose Group), respectively.

Outcome Measures

Primary Outcome Measures

  1. Number of Seroconverted Subjects for Anti-HPV-16/18 Antibodies as Assessed by Enzyme-Linked Immunosorbent Assay (ELISA) at Month 7 Based on the ATP Cohort for Immunogenicity [At Month 7 (i.e. one month after the last dose of study vaccine)]

    Seroconversion was defined as the appearance of antibodies (i.e. anti-HPV-16 and anti-HPV-18 antibody titers greater than or equal to (≥) 19 and 18 ELISA units per milliliter (EL.U/mL), respectively), in the serum of subjects seronegative before vaccination.

  2. Anti-HPV-16/18 Antibody Titers as Assessed by ELISA at Month 7 Based on the ATP Cohort for Immunogenicity [At Month 7 (i.e. one month after the last dose of study vaccine)]

    Anti-HPV 16/18 antibody titers were presented as Geometric Mean Titers (GMTs) and expressed in EL.U/mL.

  3. Anti-HPV-16/18 Antibody Titers as Assessed by ELISA at Month 7 Based on the Total Vaccinated Cohort (TVC) [At Month 7 (i.e. one month after the last dose of study vaccine)]

    Anti-HPV 16/18 antibody titers were presented as Geometric Mean Titers (GMTs) and expressed in EL.U/mL.

Secondary Outcome Measures

  1. Anti-HPV-16/18 Seroconversion Rates as Assessed by ELISA [At Day 0 and Months 12, 18, 24 and 36]

    Seroconversion was defined as the appearance of antibodies (i.e. anti-HPV-16 and anti-HPV-18 antibody titers ≥ 19 and 18 EL.U/mL, respectively) in the serum of subjects seronegative before vaccination.

  2. Anti-HPV-16/18 Antibody Titers as Assessed by ELISA [At Day 0 and Months 12, 18, 24 and 36]

    Anti-HPV 16/18 antibody titers were presented as GMTs and expressed in EL.U/mL based on ELISA.

  3. Anti-HPV-16/18 Antibody Titers as Assessed by ELISA at Month 36 [At Month 36]

    Data at Month 36 were also expressed as International Units per milliliter (IU/mL). Conversion factor from EU/mL to IU/mL was determined to be 1/6.1 for HPV-16 and 1/5.7 for HPV-18, using the WHO International Standards (NIBSC codes 05-134 and 10-140 for HPV-16 and HPV-18, respectively). The assay cut-offs were therefore 3.1 IU/mL and 3.2 IU/mL for anti-HPV-16 and anti-HPV-18 antibodies, respectively.

  4. Anti-HPV-16/18 Seroconversion Rates as Assessed by Pseudovirion-based Neutralization Assay (PBNA) in a Subset of Subjects, Based on the Month 36 ATP Cohort for Immunogenicity [At Day 0 and Months 7, 12, 18, 24 and 36]

    Seroconversion was defined as the appearance of antibodies (i.e. anti-HPV-16 and anti-HPV-18 antibody titers ≥40 ED50) in the serum of subjects seronegative before vaccination. The assay was performed on a subset of approximately 100 subjects per study group.

  5. Anti-HPV-16/18 Antibody Titers as Assessed by PBNA in a Subset of Subjects, Based on the Month 36 ATP Cohort for Immunogenicity [At Day 0 and Months 7, 12, 18, 24 and 36]

    Anti-HPV 16/18 antibody titers were presented as GMT and expressed in titers using the PBNA. The assay was performed on a subset of approximately 100 subjects per study group.

  6. Anti-HPV-16/18 Seroconversion Rates as Assessed by PBNA in a Subset of Subjects, Based on the Month 36 TVC [At Day 0 and Months 7, 12, 18, 24 and 36]

    Seroconversion was defined as the appearance of antibodies (i.e. anti-HPV-16 and anti-HPV-18 antibody titers ≥40 ED50) in the serum of subjects seronegative before vaccination. The assay was performed on a subset of approximately 100 subjects per study group.

  7. Anti-HPV-16/18 Antibody Titers as Assessed by PBNA in a Subset of Subjects, Based on the Month 36 TVC [At Day 0 and Months 7, 12, 18, 24 and 36]

    Anti-HPV 16/18 antibody titers were presented as GMT and expressed in titers using the PBNA. The assay was performed on a subset of approximately 100 subjects per study group.

  8. T-cell-mediated Immune Responses in the Sub-cohort for Cell-Mediated Immunity (CMI) [At Day 0 and Months 7, 12, 24 and 36]

    Among immune markers expressed were Interleukin-2 (IL-2), Interferon-gamma (IFN-γ), Tumour necrosis factor-alpha (TNF-α) and CD40-ligand (CD40-L). The assay was performed on a sub-cohort of approximately 100 subjects per study group.

  9. B-cell-mediated Immune Responses in the Sub-cohort for CMI [At Day 0 and Months 7, 12, 24 and 36]

    The frequency of B-cell Elispot response to HPV-16/18 by overall status was presented. The assay was performed on a sub-cohort of approximately 100 subjects per study group.

  10. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [During the 7-day period (from the day of vaccination up to 6 subsequent days) following vaccination after each dose and across doses]

    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimetres (mm) of injection site.

  11. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [During the 7-day period (from the day of vaccination up to 6 subsequent days) following vaccination after each dose and across doses]

    Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, temperature [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)] and urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever above (>) 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

  12. Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [During the 30-day (from the day of vaccination up to 29 subsequent days) post-vaccination period]

    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 was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

  13. Number of Subjects With Potentially Immune Mediated Diseases (pIMDs) [From Day 0 up to Month 12]

    pIMDs were defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

  14. Number of Subjects With Medically Significant Conditions (MSCs) [From Day 0 up to Month 36 (throughout the study period)]

    MSCs were defined as AEs prompting emergency room (ER) or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs not related to common diseases. Common diseases include: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.

  15. Number of Subjects With Serious Adverse Events (SAEs) [From Day 0 up to Month 36 (throughout the study period)]

    SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.

  16. Number of Subjects With SAEs Related to the Investigational Product, to Study Participation, to GSK Concomitant Products or Any Fatal SAE [From Day 0 up to Month 36 (throughout the study period)]

    SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. Related = an event assessed by the investigator as causally related to the investigational product, to study participation or to GSK concomitant products.

  17. Number of Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies [From Day 0 up to Month 36 (throughout the study period)]

    Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant congenital anomaly (CA), Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up and Pregnancy ongoing.

  18. Number of Subjects Using a Concomitant Medication Throughout the Study Period [From Day 0 up to Month 36 (throughout the study period) following vaccination after each dose and across doses]

    The number of subjects who have used any concomitant medication, as well as any antipyretic, any prophylactic antipyretic and any antibiotic.

  19. Number of Subjects Completing the Vaccination Schedule [From Day 0 up to Month 36 (throughout the study period)]

    The number of subjects who have completed the three-dose vaccination schedule in all groups.

Eligibility Criteria

Criteria

Ages Eligible for Study:
9 Years to 14 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:

  • Subjects who the investigator believes can and will comply with the requirements of the protocol and subjects who the investigator believes their parent(s)/Legally Acceptable Representative(s) (LAR[s]) can and will comply with the requirements of the protocol.

  • A female between, and including, 9 and 14 years of age at the time of the first vaccination.

  • Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to enrolment in the study. In addition, if capable, the subject should sign and personally date a written informed assent.

  • Healthy subjects as established by medical history and clinical examination before entering into the study.

  • Female subjects of non-childbearing potential may be enrolled in the study.

  • Female subjects of childbearing potential may be enrolled in the study, if the subject:

  • has practiced adequate contraception for 30 days prior to vaccination, and

  • has a negative pregnancy test on the day of vaccination, and

  • has agreed to continue adequate contraception during the entire treatment period and for two months after completion of the vaccination series.

Exclusion Criteria:

  • Pregnant or breastfeeding.

  • A woman planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the vaccination phase of the study, i.e. up to two months after the last vaccine dose.

  • Previous vaccination against HPV or planned administration of another HPV vaccine during the study other than those foreseen in the protocol.

  • Child in care.

  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 36).

  • Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.

  • History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccines.

  • Cancer or autoimmune disease under treatment.

  • Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before each dose of vaccine. Administration of routine meningococcal, hepatitis B, hepatitis A, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccine up to 8 days before each dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window.

  • Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).

  • Previous administration of vaccine components.

  • Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

  • Family history of congenital or hereditary immunodeficiency.

  • Major congenital defects or serious chronic illness.

  • Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests, which in the opinion of the investigator precludes administration of the study vaccine.

  • Acute disease and/or fever at the time of enrolment.

  • Drug and/or alcohol abuse.

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Dax France 40100
2 GSK Investigational Site Draguignan France 83300
3 GSK Investigational Site Essey les Nancy France 54270
4 GSK Investigational Site Le Havre France 76620
5 GSK Investigational Site Nice France 06300
6 GSK Investigational Site Paris cedex 20 France 75970
7 GSK Investigational Site Rosiers d'Egletons France 19300
8 GSK Investigational Site Saint Cyr Sur Loir France 37540
9 GSK Investigational Site Seysses France 31600
10 GSK Investigational Site Tours France 37100
11 GSK Investigational Site Pokfulam Hong Kong
12 GSK Investigational Site Shatin Hong Kong
13 GSK Investigational Site Singapore Singapore 119074
14 GSK Investigational Site Singapore Singapore 169608
15 GSK Investigational Site Singapore Singapore 228510
16 GSK Investigational Site Singapore Singapore 229899
17 GSK Investigational Site Singapore Singapore 529889
18 GSK Investigational Site Singapore Singapore 768826
19 GSK Investigational Site Eskilstuna Sweden SE-631 88
20 GSK Investigational Site Linköping Sweden SE-581 85
21 GSK Investigational Site Örebro Sweden SE-701 16

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01462357
Other Study ID Numbers:
  • 115411
  • 2011-002035-26
First Posted:
Oct 31, 2011
Last Update Posted:
Nov 15, 2019
Last Verified:
Oct 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by GlaxoSmithKline
Human papillomavirus
Safety
HPV vaccine
Immune response

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail 1079 subjects entered this study, of which 4 subjects signed an informed consent but did not receive a single dose of the vaccine and were hence not counted as starting the study.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Period Title: Overall Study
STARTED 359 358 358
COMPLETED 351 339 346
NOT COMPLETED 8 19 12

Baseline Characteristics

Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group Total
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Total of all reporting groups
Overall Participants 359 358 358 1075
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
11.5
(1.64)
11.5
(1.56)
11.6
(1.64)
11.53
(1.61)
Sex: Female, Male (Count of Participants)
Female
359
100%
358
100%
358
100%
1075
100%
Male
0
0%
0
0%
0
0%
0
0%
Race/Ethnicity, Customized (Count of Participants)
African Heritage / African American
4
1.1%
6
1.7%
4
1.1%
14
1.3%
Asian - Central / South Asian Heritage
1
0.3%
1
0.3%
2
0.6%
4
0.4%
Asian - East Asian Heritage
179
49.9%
178
49.7%
179
50%
536
49.9%
Asian - South East Asian Heritage
81
22.6%
78
21.8%
83
23.2%
242
22.5%
White - Arabic / North African Heritage
5
1.4%
7
2%
7
2%
19
1.8%
White - Caucasian / European Heritage
89
24.8%
86
24%
83
23.2%
258
24%
White - Caucasian / African Heritage
0
0%
1
0.3%
0
0%
1
0.1%
African - White / Caucasian Heritage
0
0%
1
0.3%
0
0%
1
0.1%

Outcome Measures

1. Primary Outcome
Title Number of Seroconverted Subjects for Anti-HPV-16/18 Antibodies as Assessed by Enzyme-Linked Immunosorbent Assay (ELISA) at Month 7 Based on the ATP Cohort for Immunogenicity
Description Seroconversion was defined as the appearance of antibodies (i.e. anti-HPV-16 and anti-HPV-18 antibody titers greater than or equal to (≥) 19 and 18 ELISA units per milliliter (EL.U/mL), respectively), in the serum of subjects seronegative before vaccination.
Time Frame At Month 7 (i.e. one month after the last dose of study vaccine)

Outcome Measure Data

Analysis Population Description
The analysis was based on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available at the specified time point and who were seronegative before vaccination.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 334 331 333
Anti-HPV-16
330
91.9%
327
91.3%
322
89.9%
Anti-HPV-18
334
93%
331
92.5%
333
93%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cervarix 2 Dose Group, Gardasil 2 Dose Group
Comments Immune response to anti-HPV-16 in terms of seroconversion rates (SCR): To evaluate sequentially if the immunogenicity (as determined by ELISA) of Cervarix vaccine administered according to a 2-dose schedule at 0, 6 months is non-inferior to that of Gardasil vaccine administered according to a 2-dose schedule at 0, 6 months, 1 month after the last dose (Month 7), in initially seronegative subjects.
Type of Statistical Test Non-Inferiority
Comments Non-inferiority with respect to seroconversion was shown if, one month after the last dose, for both anti-HPV-16 and anti-HPV-18 antibodies, the upper limit of the 95% confidence interval (CI) for the difference (Gardasil 2 dose Group minus Cervarix 2 dose Group) was below 5%.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference in SCR
Estimated Value 0
Confidence Interval (2-Sided) 95%
-1.16 to 1.15
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cervarix 2 Dose Group, Gardasil 2 Dose Group
Comments Immune response to anti-HPV-18 in terms of SCR: To evaluate sequentially if the immunogenicity (as determined by ELISA) of Cervarix vaccine administered according to a 2-dose schedule at 0, 6 months is non-inferior to that of Gardasil vaccine administered according to a 2-dose schedule at 0, 6 months, 1 month after the last dose (Month 7), in initially seronegative subjects.
Type of Statistical Test Non-Inferiority
Comments Non-inferiority with respect to seroconversion was shown if, one month after the last dose, for both anti-HPV-16 and anti-HPV-18 antibodies, the upper limit of the 95% confidence interval (CI) for the difference (Gardasil 2 dose Group minus Cervarix 2 dose Group) was below 5%.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Difference in SCR
Estimated Value 0
Confidence Interval (2-Sided) 95%
-1.15 to 1.14
Parameter Dispersion Type:
Value:
Estimation Comments
2. Primary Outcome
Title Anti-HPV-16/18 Antibody Titers as Assessed by ELISA at Month 7 Based on the ATP Cohort for Immunogenicity
Description Anti-HPV 16/18 antibody titers were presented as Geometric Mean Titers (GMTs) and expressed in EL.U/mL.
Time Frame At Month 7 (i.e. one month after the last dose of study vaccine)

Outcome Measure Data

Analysis Population Description
The analysis was based on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom immunogenicity data were available at the specified time point and who were seronegative before vaccination.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 334 331 333
Anti-HPV-16
8244.1
5056.0
4807.4
Anti-HPV-18
5277.4
1207.2
1653.5
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cervarix 2 Dose Group, Gardasil 2 Dose Group
Comments Immune response to anti-HPV-16 in terms of Geometric Mean Titers (GMT): To evaluate sequentially if the immunogenicity (as determined by ELISA) of Cervarix vaccine administered according to a 2-dose schedule at 0, 6 months is non-inferior to that of Gardasil vaccine administered according to a 2-dose schedule at 0, 6 months, 1 month after the last dose (Month 7), in initially seronegative subjects.
Type of Statistical Test Non-Inferiority
Comments Non-inferiority with respect to GMT was shown if, one month after the last dose, for both anti-HPV-16 and anti-HPV-18 antibodies, the upper limit of the 95% CI for the GMT ratio (Gardasil 2 dose Group divided by Cervarix 2 dose Group) was below 2.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.54 to 0.69
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cervarix 2 Dose Group, Gardasil 2 Dose Group
Comments Immune response to anti-HPV-18 in terms of GMT: To evaluate sequentially if the immunogenicity (as determined by ELISA) of Cervarix vaccine administered according to a 2-dose schedule at 0, 6 months is non-inferior to that of Gardasil vaccine administered according to a 2-dose schedule at 0, 6 months, 1 month after the last dose (Month 7), in initially seronegative subjects.
Type of Statistical Test Non-Inferiority
Comments Non-inferiority with respect to GMT was shown if, one month after the last dose, for both anti-HPV-16 and anti-HPV-18 antibodies, the upper limit of the 95% confidence interval (CI) for the GMT ratio (Gardasil 2 dose Group divided by Cervarix 2 dose Group) was below 2.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
0.20 to 0.26
Parameter Dispersion Type:
Value:
Estimation Comments
3. Primary Outcome
Title Anti-HPV-16/18 Antibody Titers as Assessed by ELISA at Month 7 Based on the Total Vaccinated Cohort (TVC)
Description Anti-HPV 16/18 antibody titers were presented as Geometric Mean Titers (GMTs) and expressed in EL.U/mL.
Time Frame At Month 7 (i.e. one month after the last dose of study vaccine)

Outcome Measure Data

Analysis Population Description
The analysis was based on the TVC which included all subjects, regardless of serostatus, who received at least one dose of vaccine in this study and for whom data were available at the specified time point.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 357 353 351
Anti-HPV-16
8256.4
4886.1
4789.2
Anti-HPV-18
5267.8
1166.3
1635.8
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cervarix 2 Dose Group, Gardasil 2 Dose Group
Comments Anti-HPV-18 immune response: To evaluate sequentially if the immunogenicity (as determined by ELISA) of Cervarix vaccine administered according to a 2-dose schedule at 0, 6 months is superior to that of Gardasil vaccine administered according to a 2-dose schedule at 0, 6 months, in 9-14 year-old females, 1 month after the last dose (Month 7) regardless of serostatus.
Type of Statistical Test Superiority
Comments Superiority was shown if the lower limit of the 95% CI for the ratio of GMTs (Cervarix 2 dose Group divided by Gardasil 2 dose Group) was above 1 for anti-HPV-18 antibodies.
Statistical Test of Hypothesis p-Value 0.0001
Comments
Method ANOVA
Comments
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 4.52
Confidence Interval (2-Sided) 95%
3.97 to 5.13
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cervarix 2 Dose Group, Gardasil 2 Dose Group
Comments Anti-HPV-16 immune response: To evaluate sequentially if the immunogenicity (as determined by ELISA) of Cervarix vaccine administered according to a 2-dose schedule at 0, 6 months is superior to that of Gardasil vaccine administered according to a 2-dose schedule at 0, 6 months, in 9-14 year-old females, 1 month after the last dose (Month 7) regardless of serostatus.
Type of Statistical Test Superiority
Comments Superiority was shown if the lower limit of the 95% CI for the ratio of GMTs (Cervarix 2 dose Group divided by Gardasil 2 dose Group) was above 1 for anti-HPV-16 antibodies.
Statistical Test of Hypothesis p-Value 0.0001
Comments
Method ANOVA
Comments
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.69
Confidence Interval (2-Sided) 95%
1.49 to 1.91
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Anti-HPV-16/18 Seroconversion Rates as Assessed by ELISA
Description Seroconversion was defined as the appearance of antibodies (i.e. anti-HPV-16 and anti-HPV-18 antibody titers ≥ 19 and 18 EL.U/mL, respectively) in the serum of subjects seronegative before vaccination.
Time Frame At Day 0 and Months 12, 18, 24 and 36

Outcome Measure Data

Analysis Population Description
The analysis was based on the Month 36 ATP cohort for immunogenicity, which included subjects who returned for blood sampling at Month 36, for whom data concerning immunogenicity outcome measures were available at the specified time points and who were seronegative before vaccination.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 322 310 320
Anti-HPV-16, Day 0
0
0%
0
0%
0
0%
Anti-HPV-18, Day 0
0
0%
0
0%
0
0%
Anti-HPV-16, Month 12
316
88%
305
85.2%
308
86%
Anti-HPV-18, Month 12
320
89.1%
309
86.3%
319
89.1%
Anti-HPV-16, Month 18
316
88%
304
84.9%
309
86.3%
Anti-HPV-18, Month 18
320
89.1%
294
82.1%
313
87.4%
Anti-HPV-16, Month 24
314
87.5%
303
84.6%
307
85.8%
Anti-HPV-18, Month 24
318
88.6%
287
80.2%
308
86%
Anti-HPV-16, Month 36
318
88.6%
304
84.9%
308
86%
Anti-HPV-18, Month 36
322
89.7%
267
74.6%
297
83%
5. Secondary Outcome
Title Anti-HPV-16/18 Antibody Titers as Assessed by ELISA
Description Anti-HPV 16/18 antibody titers were presented as GMTs and expressed in EL.U/mL based on ELISA.
Time Frame At Day 0 and Months 12, 18, 24 and 36

Outcome Measure Data

Analysis Population Description
The analysis was based on the Month 36 ATP cohort for immunogenicity, which included subjects who returned for blood sampling at Month 36, for whom data concerning immunogenicity outcome measures were available at the specified time points and who were seronegative before vaccination.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 322 310 320
Anti-HPV-16, Day 0
9.5
9.5
9.5
Anti-HPV-18, Day 0
9.0
9.0
9.0
Anti-HPV-16, Month 12
2209.2
1294.8
1600.7
Anti-HPV-18, Month 12
1299.3
266.6
478.5
Anti-HPV-16, Month 18
1488.8
684.4
824.0
Anti-HPV-18, Month 18
754.2
134.8
231.3
Anti-HPV-16, Month 24
1285.0
514.1
637.1
Anti-HPV-18, Month 24
613.7
106.3
182.0
Anti-HPV-16, Month 36
1061.4
379.8
472.4
Anti-HPV-18, Month 36
486.5
71.0
119.1
6. Secondary Outcome
Title Anti-HPV-16/18 Antibody Titers as Assessed by ELISA at Month 36
Description Data at Month 36 were also expressed as International Units per milliliter (IU/mL). Conversion factor from EU/mL to IU/mL was determined to be 1/6.1 for HPV-16 and 1/5.7 for HPV-18, using the WHO International Standards (NIBSC codes 05-134 and 10-140 for HPV-16 and HPV-18, respectively). The assay cut-offs were therefore 3.1 IU/mL and 3.2 IU/mL for anti-HPV-16 and anti-HPV-18 antibodies, respectively.
Time Frame At Month 36

Outcome Measure Data

Analysis Population Description
The analysis was based on the Month 36 ATP cohort for immunogenicity, which included subjects who returned for blood sampling at Month 36, for whom data concerning immunogenicity outcome measures were available at the specified time point and who were seronegative before vaccination.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 322 310 320
Anti-HPV-16
174.0
62.3
77.4
Anti-HPV-18
85.3
12.5
20.9
7. Secondary Outcome
Title Anti-HPV-16/18 Seroconversion Rates as Assessed by Pseudovirion-based Neutralization Assay (PBNA) in a Subset of Subjects, Based on the Month 36 ATP Cohort for Immunogenicity
Description Seroconversion was defined as the appearance of antibodies (i.e. anti-HPV-16 and anti-HPV-18 antibody titers ≥40 ED50) in the serum of subjects seronegative before vaccination. The assay was performed on a subset of approximately 100 subjects per study group.
Time Frame At Day 0 and Months 7, 12, 18, 24 and 36

Outcome Measure Data

Analysis Population Description
The analysis was based on the Month 36 ATP cohort for immunogenicity, which included a subset of approximately 100 subjects per study group, who returned for blood sampling at Month 36, for whom immunogenicity data were available at the specified time point and who were seronegative before vaccination.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 89 87 91
Anti-HPV-16, Day 0
0
0%
0
0%
0
0%
Anti-HPV-18, Day 0
0
0%
0
0%
0
0%
Anti-HPV-16, Month 7
89
24.8%
85
23.7%
91
25.4%
Anti-HPV-18, Month 7
89
24.8%
87
24.3%
91
25.4%
Anti-HPV-16, Month 12
88
24.5%
85
23.7%
91
25.4%
Anti-HPV-18, Month 12
88
24.5%
86
24%
91
25.4%
Anti-HPV-16, Month 18
88
24.5%
83
23.2%
89
24.9%
Anti-HPV-18, Month 18
87
24.2%
77
21.5%
89
24.9%
Anti-HPV-16, Month 24
86
24%
83
23.2%
90
25.1%
Anti-HPV-18, Month 24
86
24%
75
20.9%
88
24.6%
Anti-HPV-16, Month 36
89
24.8%
85
23.7%
91
25.4%
Anti-HPV-18, Month 36
89
24.8%
75
20.9%
86
24%
8. Secondary Outcome
Title Anti-HPV-16/18 Antibody Titers as Assessed by PBNA in a Subset of Subjects, Based on the Month 36 ATP Cohort for Immunogenicity
Description Anti-HPV 16/18 antibody titers were presented as GMT and expressed in titers using the PBNA. The assay was performed on a subset of approximately 100 subjects per study group.
Time Frame At Day 0 and Months 7, 12, 18, 24 and 36

Outcome Measure Data

Analysis Population Description
The analysis was based on the Month 36 ATP cohort for immunogenicity, which included a subset of approximately 100 subjects per study group, who returned for blood sampling at Month 36, for whom immunogenicity data were available at the specified time point and who were seronegative before vaccination.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 89 87 91
Anti-HPV-16, Day 0
20.0
20.0
20.0
Anti-HPV-18, Day 0
20.0
20.0
20.0
Anti-HPV-16, Month 7
52868.5
19130.1
22182.7
Anti-HPV-18, Month 7
24068.5
4726.5
8243.9
Anti-HPV-16, Month 12
10695.9
4280.1
5843.8
Anti-HPV-18, Month 12
3683.3
689.0
1788.6
Anti-HPV-16, Month 18
8436.3
2129.7
2987.2
Anti-HPV-18, Month 18
2426.3
295.7
812.1
Anti-HPV-16, Month 24
5036.7
1211.8
1967.2
Anti-HPV-18, Month 24
1763.0
237.1
573.1
Anti-HPV-16, Month 36
4357.8
1128.9
1577.0
Anti-HPV-18, Month 36
1613.9
185.8
472.8
9. Secondary Outcome
Title Anti-HPV-16/18 Seroconversion Rates as Assessed by PBNA in a Subset of Subjects, Based on the Month 36 TVC
Description Seroconversion was defined as the appearance of antibodies (i.e. anti-HPV-16 and anti-HPV-18 antibody titers ≥40 ED50) in the serum of subjects seronegative before vaccination. The assay was performed on a subset of approximately 100 subjects per study group.
Time Frame At Day 0 and Months 7, 12, 18, 24 and 36

Outcome Measure Data

Analysis Population Description
The analysis was based on the Month 36 TVC, which included a subset of approximately 100 subjects per study group, who received at least one dose of vaccine in this study, for whom data were available at the specified time points and who were seronegative before vaccination.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 99 92 98
Anti-HPV-16, Day 0
0
0%
0
0%
0
0%
Anti-HPV-18, Day 0
0
0%
0
0%
0
0%
Anti-HPV-16, Month 7
99
27.6%
90
25.1%
98
27.4%
Anti-HPV-18, Month 7
99
27.6%
92
25.7%
98
27.4%
Anti-HPV-16, Month 12
97
27%
90
25.1%
98
27.4%
Anti-HPV-18, Month 12
98
27.3%
91
25.4%
98
27.4%
Anti-HPV-16, Month 18
97
27%
88
24.6%
96
26.8%
Anti-HPV-18, Month 18
97
27%
82
22.9%
96
26.8%
Anti-HPV-16, Month 24
95
26.5%
87
24.3%
97
27.1%
Anti-HPV-18, Month 24
96
26.7%
79
22.1%
94
26.3%
Anti-HPV-16, Month 36
97
27%
90
25.1%
98
27.4%
Anti-HPV-18, Month 36
97
27%
80
22.3%
92
25.7%
10. Secondary Outcome
Title Anti-HPV-16/18 Antibody Titers as Assessed by PBNA in a Subset of Subjects, Based on the Month 36 TVC
Description Anti-HPV 16/18 antibody titers were presented as GMT and expressed in titers using the PBNA. The assay was performed on a subset of approximately 100 subjects per study group.
Time Frame At Day 0 and Months 7, 12, 18, 24 and 36

Outcome Measure Data

Analysis Population Description
The analysis was based on the Month 36 TVC, which included a subset of approximately 100 subjects per study group, who received at least one dose of vaccine in this study, for whom data were available at the specified time points and who were seronegative before vaccination.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 99 92 98
Anti-HPV-16, Day 0
20.0
20.0
20.0
Anti-HPV-18, Day 0
20.0
20.0
20.0
Anti-HPV-16, Month 7
50000.7
18573.7
22294.2
Anti-HPV-18, Month 7
23576.9
4563.7
8042.1
Anti-HPV-16, Month 12
10039.6
4174.9
5766.0
Anti-HPV-18, Month 12
3546.9
670.3
1801.4
Anti-HPV-16, Month 18
7508.8
2070.2
2961.5
Anti-HPV-18, Month 18
2240.5
294.5
797.6
Anti-HPV-16, Month 24
4609.1
1193.9
1932.0
Anti-HPV-18, Month 24
1638.6
239.7
564.6
Anti-HPV-16, Month 36
4011.7
1111.4
1517.2
Anti-HPV-18, Month 36
1513.7
185.8
468.6
11. Secondary Outcome
Title T-cell-mediated Immune Responses in the Sub-cohort for Cell-Mediated Immunity (CMI)
Description Among immune markers expressed were Interleukin-2 (IL-2), Interferon-gamma (IFN-γ), Tumour necrosis factor-alpha (TNF-α) and CD40-ligand (CD40-L). The assay was performed on a sub-cohort of approximately 100 subjects per study group.
Time Frame At Day 0 and Months 7, 12, 24 and 36

Outcome Measure Data

Analysis Population Description
The analysis was based on the Month 36 ATP cohort for immunogenicity, which included a sub-cohort of approximately 100 subjects per study group, who returned for blood sampling at Month 36 and for whom data concerning immunogenicity outcome measures were available at the specified time point.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 67 60 74
CD4+ All doubles, Anti-HPV-16, Day 0
10
22
33
CD4+ All doubles, Anti-HPV-18, Day 0
28
47.5
26
CD4+ All doubles, Anti-HPV-16, Month 7
1662
872
1121
CD4+ All doubles, Anti-HPV-18, Month 7
897
427
640
CD4+ All doubles, Anti-HPV-16, Month 12
916
585.5
819.5
CD4+ All doubles, Anti-HPV-18, Month 12
789
327
446
CD4+ All doubles, Anti-HPV-16, Month 24
1068.5
750.5
968.5
CD4+ All doubles, Anti-HPV-18, Month 24
645
352
578
CD4+ All doubles, Anti-HPV-16, Month 36
1012
685
842.5
CD4+ All doubles, Anti-HPV-18, Month 36
682
350
516
CD4-d-CD40L, Anti-HPV-16, Day 0
1
14
30
CD4-d-CD40L, Anti-HPV-18, Day 0
14
39.5
27.5
CD4-d-CD40L, Anti-HPV-16, Month 7
1515
779
1025.5
CD4-d-CD40L, Anti-HPV-18, Month 7
866
386.5
574
CD4-d-CD40L, Anti-HPV-16, Month 12
889
524
761.5
CD4-d-CD40L, Anti-HPV-18, Month 12
688
317
383.5
CD4-d-CD40L, Anti-HPV-16, Month 24
1045.5
736
937
CD4-d-CD40L, Anti-HPV-18, Month 24
639
332
564
CD4-d-CD40L, Anti-HPV-16, Month 36
957
685
778.5
CD4-d-CD40L, Anti-HPV-18, Month 36
671
337
499
CD4-d- IFNγ, Anti-HPV-16, Day 0
12
19
1
CD4-d- IFNγ, Anti-HPV-18, Day 0
14
13.5
3.5
CD4-d- IFNγ, Anti-HPV-16, Month 7
365
320
422.5
CD4-d- IFNγ, Anti-HPV-18, Month 7
242
133.5
181
CD4-d- IFNγ, Anti-HPV-16, Month 12
326
235
356
CD4-d- IFNγ, Anti-HPV-18, Month 12
175
112
164
CD4-d- IFNγ, Anti-HPV-16, Month 24
300.5
317.5
421
CD4-d- IFNγ, Anti-HPV-18, Month 24
171
112
220
CD4-d-IFNγ, Anti-HPV-16, Month 36
253.5
301
270.5
CD4-d-IFNγ, Anti-HPV-18, Month 36
193
109
155
CD4-d-IL-2, Anti-HPV-16, Day 0
14
25
33
CD4-d-IL-2, Anti-HPV-18, Day 0
1
36.5
22
CD4-d-IL-2, Anti-HPV-16, Month 7
1357
712.5
866
CD4-d-IL-2, Anti-HPV-18, Month 7
737
304
486
CD4-d-IL-2, Anti-HPV-16, Month 12
832
479
674.5
CD4-d-IL-2, Anti-HPV-18, Month 12
620
259
354
CD4-d-IL-2, Anti-HPV-16, Month 24
855
579.5
700
CD4-d-IL-2, Anti-HPV-18, Month 24
494
240
426
CD4-d-IL-2, Anti-HPV-16, Month 36
784
517
680
CD4-d-IL-2, Anti-HPV-18, Month 36
507
274
341
CD4-d-TNFα, Anti-HPV-16, Day 0
6
33
16
CD4-d-TNFα, Anti-HPV-18, Day 0
27
22.5
23
CD4-d-TNFα, Anti-HPV-16, Month 7
1111
625
796
CD4-d-TNFα, Anti-HPV-18, Month 7
647
283.5
457
CD4-d-TNFα, Anti-HPV-16, Month 12
790
482
716
CD4-d-TNFα, Anti-HPV-18, Month 12
674
266
384.5
CD4-d-TNFα, Anti-HPV-16, Month 24
795.5
563.5
760.5
CD4-d-TNFα, Anti-HPV-18, Month 24
510
239
522
CD4-d-TNFα, Anti-HPV-16, Month 36
786.5
547
724.5
CD4-d-TNFα, Anti-HPV-18, Month 36
588
301
479
CD8-All Doubles, Anti-HPV-16, Day 0
1
4
1
CD8-All Doubles, Anti-HPV-18, Day 0
1
1
1
CD8-All Doubles, Anti-HPV-16, Month 7
1
1
1
CD8-All Doubles, Anti-HPV-18, Month 7
1
1
1
CD8-All Doubles, Anti-HPV-16, Month 12
1
1
1
CD8-All Doubles, Anti-HPV-18, Month 12
1
1
1
CD8-All Doubles, Anti-HPV-16, Month 24
1
1
1
CD8-All Doubles, Anti-HPV-18, Month 24
1
1
1
CD8-All doubles, Anti-HPV-16, Month 36
1
1
1
CD8-All doubles, Anti-HPV-18, Month 36
4
2
1
CD8-d-CD40L, Anti-HPV-16, Day 0
1
1
1
CD8-d-CD40L, Anti-HPV-18, Day 0
1
1
1
CD8-d-CD40L, Anti-HPV-16, Month 7
1
1
1
CD8-d-CD40L, Anti-HPV-18, Month 7
1
1
1
CD8-d-CD40L, Anti-HPV-16, Month 12
1
1
1
CD8-d-CD40L, Anti-HPV-18, Month 12
1
1
1
CD8-d-CD40L, Anti-HPV-16, Month 24
1
1
1
CD8-d-CD40L, Anti-HPV-18, Month 24
1
1
1
CD8-d-CD40L, Anti-HPV-16, Month 36
1
1
1
CD8-d-CD40L, Anti-HPV-18, Month 36
1
1
1
CD8-d-IFNγ, Anti-HPV-16, Day 0
1
1
1
CD8-d-IFNγ, Anti-HPV-18, Day 0
1
1
1
CD8-d-IFNγ, Anti-HPV-16, Month 7
1
1
1
CD8-d-IFNγ, Anti-HPV-18, Month 7
1
1
1
CD8-d-IFNγ, Anti-HPV-16, Month 12
1
1
1
CD8-d-IFNγ, Anti-HPV-18, Month 12
1
1
1
CD8-d-IFNγ, Anti-HPV-16, Month 24
1
1
1
CD8-d-IFNγ, Anti-HPV-18, Month 24
1
1
1
CD8-d-IFNγ, Anti-HPV-16, Month 36
1
1
1
CD8-d-IFNγ, Anti-HPV-18, Month 36
1
2
1
CD8-d-IL-2, Anti-HPV-16, Day 0
1
1
1
CD8-d-IL-2, Anti-HPV-18, Day 0
1
1
1
CD8-d-IL-2, Anti-HPV-16, Month 7
1
1
1
CD8-d-IL-2, Anti-HPV-18, Month 7
1
1
1
CD8-d-IL-2, Anti-HPV-16, Month 12
1
1
1
CD8-d-IL-2, Anti-HPV-18, Month 12
1
1
1
CD8-d-IL-2, Anti-HPV-16, Month 24
1
1
1
CD8-d-IL-2, Anti-HPV-18, Month 24
1
1
1
CD8-d-IL-2, Anti-HPV-16, Month 36
1
1
1
CD8-d-IL-2, Anti-HPV-18, Month 36
1
1
1
CD8-d-TNFα, Anti-HPV-16, Day 0
1
1
1
CD8-d-TNFα, Anti-HPV-18, Day 0
1
1
1
CD8-d-TNFα, Anti-HPV-16, Month 7
1
1
1
CD8-d-TNFα, Anti-HPV-18, Month 7
1
1
1
CD8-d-TNFα, Anti-HPV-16, Month 12
1
1
1
CD8-d-TNFα, Anti-HPV-18, Month 12
1
1
1
CD8-d-TNFα, Anti-HPV-16, Month 24
1
1
1
CD8-d-TNFα, Anti-HPV-18, Month 24
1
1
1
CD8-d-TNFα, Anti-HPV-16, Month 36
1
1
1
CD8-d-TNFα, Anti-HPV-18, Month 36
1
1
1
12. Secondary Outcome
Title B-cell-mediated Immune Responses in the Sub-cohort for CMI
Description The frequency of B-cell Elispot response to HPV-16/18 by overall status was presented. The assay was performed on a sub-cohort of approximately 100 subjects per study group.
Time Frame At Day 0 and Months 7, 12, 24 and 36

Outcome Measure Data

Analysis Population Description
The analysis was based on the Month 36 ATP cohort for immunogenicity, which included a sub-cohort of approximately 100 subjects per study group, who returned for blood sampling at Month 36 and for whom data concerning immunogenicity outcome measures were available at the specified time point.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 71 65 76
HPV-16, Day 0
1
1
1
HPV-18, Day 0
1
1
1
HPV-16, Month 7
1733
1254
733
HPV-18, Month 7
558
155
111
HPV-16, Month 12
408
278
289
HPV-18, Month 12
249
69
69
HPV-16, Month 24
270
218.5
249
HPV-18, Month 24
128.5
57.5
111
HPV-16, Month 36
353
382.5
246
HPV-18, Month 36
116
25
63
13. Secondary Outcome
Title Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimetres (mm) of injection site.
Time Frame During the 7-day period (from the day of vaccination up to 6 subsequent days) following vaccination after each dose and across doses

Outcome Measure Data

Analysis Population Description
The analysis was based on the TVC, which included all subjects with at least one study vaccine administered and who had their symptom sheet completed.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 359 357 356
Any Pain - Dose 1
311
86.6%
235
65.6%
231
64.5%
Any Pain - Dose 2
193
53.8%
183
51.1%
215
60.1%
Any Pain - Dose 3
280
78%
194
54.2%
222
62%
Any Pain - Across doses
329
91.6%
276
77.1%
295
82.4%
Grade 3 Pain - Dose 1
22
6.1%
4
1.1%
6
1.7%
Grade 3 Pain - Dose 2
8
2.2%
8
2.2%
8
2.2%
Grade 3 Pain - Dose 3
23
6.4%
11
3.1%
10
2.8%
Grade 3 Pain - Across doses
42
11.7%
17
4.7%
18
5%
Any Redness - Dose 1
137
38.2%
84
23.5%
87
24.3%
Any Redness - Dose 2
100
27.9%
84
23.5%
99
27.7%
Any Redness - Dose 3
133
37%
92
25.7%
102
28.5%
Any Redness - Across doses
191
53.2%
134
37.4%
157
43.9%
Grade 3 Redness - Dose 1
0
0%
0
0%
1
0.3%
Grade 3 Redness - Dose 2
0
0%
0
0%
0
0%
Grade 3 Redness - Dose 3
0
0%
0
0%
1
0.3%
Grade 3 Redness - Across doses
0
0%
0
0%
2
0.6%
Any Swelling - Dose 1
112
31.2%
44
12.3%
39
10.9%
Any Swelling - Dose 2
63
17.5%
35
9.8%
76
21.2%
Any Swelling - Dose 3
113
31.5%
67
18.7%
85
23.7%
Any Swelling - Across doses
163
45.4%
98
27.4%
118
33%
Grade 3 Swelling - Dose 1
3
0.8%
0
0%
0
0%
Grade 3 Swelling - Dose 2
0
0%
0
0%
0
0%
Grade 3 Swelling - Dose 3
2
0.6%
0
0%
2
0.6%
Grade 3 Swelling - Across doses
5
1.4%
0
0%
2
0.6%
14. Secondary Outcome
Title Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, temperature [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)] and urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever above (>) 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
Time Frame During the 7-day period (from the day of vaccination up to 6 subsequent days) following vaccination after each dose and across doses

Outcome Measure Data

Analysis Population Description
The analysis was based on the TVC, which included all subjects with at least one study vaccine administered and who had their symptom sheet completed.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 359 357 356
Any Arthralgia - Dose 1
44
12.3%
50
14%
39
10.9%
Any Arthralgia - Dose 2
23
6.4%
30
8.4%
34
9.5%
Any Arthralgia - Dose 3
31
8.6%
38
10.6%
35
9.8%
Any Arthralgia - Across doses
68
18.9%
81
22.6%
67
18.7%
Grade 3 Arthralgia - Dose 1
5
1.4%
1
0.3%
1
0.3%
Grade 3 Arthralgia - Dose 2
1
0.3%
2
0.6%
1
0.3%
Grade 3 Arthralgia - Dose 3
2
0.6%
3
0.8%
1
0.3%
Grade 3 Arthralgia - Across doses
6
1.7%
4
1.1%
1
0.3%
Related Arthralgia - Dose 1
29
8.1%
32
8.9%
28
7.8%
Related Arthralgia - Dose 2
17
4.7%
17
4.7%
18
5%
Related Arthralgia - Dose 3
20
5.6%
27
7.5%
27
7.5%
Related Arthralgia - Across doses
51
14.2%
55
15.4%
51
14.2%
Any Fatigue - Dose 1
163
45.4%
157
43.9%
168
46.9%
Any Fatigue - Dose 2
103
28.7%
104
29.1%
119
33.2%
Any Fatigue - Dose 3
108
30.1%
97
27.1%
103
28.8%
Any Fatigue - Across doses
192
53.5%
199
55.6%
193
53.9%
Grade 3 Fatigue - Dose 1
7
1.9%
10
2.8%
5
1.4%
Grade 3 Fatigue - Dose 2
12
3.3%
3
0.8%
2
0.6%
Grade 3 Fatigue - Dose 3
7
1.9%
3
0.8%
3
0.8%
Grade 3 Fatigue - Across doses
18
5%
15
4.2%
7
2%
Related Fatigue - Dose 1
103
28.7%
102
28.5%
98
27.4%
Related Fatigue - Dose 2
68
18.9%
66
18.4%
67
18.7%
Related Fatigue - Dose 3
70
19.5%
67
18.7%
67
18.7%
Related Fatigue - Across doses
152
42.3%
151
42.2%
143
39.9%
Any Gastrointestinal - Dose 1
34
9.5%
52
14.5%
44
12.3%
Any Gastrointestinal - Dose 2
19
5.3%
22
6.1%
23
6.4%
Any Gastrointestinal - Dose 3
16
4.5%
29
8.1%
24
6.7%
Any Gastrointestinal - Across doses
55
15.3%
74
20.7%
70
19.6%
Grade 3 Gastrointestinal - Dose 1
3
0.8%
2
0.6%
2
0.6%
Grade 3 Gastrointestinal - Dose 2
2
0.6%
1
0.3%
0
0%
Grade 3 Gastrointestinal - Dose 3
1
0.3%
4
1.1%
2
0.6%
Grade 3 Gastrointestinal - Across doses
5
1.4%
6
1.7%
3
0.8%
Related Gastrointestinal - Dose 1
21
5.8%
26
7.3%
22
6.1%
Related Gastrointestinal - Dose 2
8
2.2%
17
4.7%
6
1.7%
Related Gastrointestinal - Dose 3
10
2.8%
20
5.6%
17
4.7%
Related Gastrointestinal - Across doses
32
8.9%
49
13.7%
40
11.2%
Any Headache - Dose 1
102
28.4%
87
24.3%
90
25.1%
Any Headache - Dose 2
62
17.3%
64
17.9%
73
20.4%
Any Headache - Dose 3
63
17.5%
54
15.1%
65
18.2%
Any Headache - Across doses
147
40.9%
133
37.2%
151
42.2%
Grade 3 Headache - Dose 1
7
1.9%
6
1.7%
1
0.3%
Grade 3 Headache - Dose 2
6
1.7%
2
0.6%
4
1.1%
Grade 3 Headache - Dose 3
7
1.9%
1
0.3%
1
0.3%
Grade 3 Headache - Across doses
17
4.7%
7
2%
4
1.1%
Related Headache - Dose 1
61
17%
51
14.2%
48
13.4%
Related Headache - Dose 2
39
10.9%
37
10.3%
41
11.5%
Related Headache - Dose 3
45
12.5%
33
9.2%
42
11.7%
Related Headache - Across doses
107
29.8%
88
24.6%
100
27.9%
Any Myalgia - Dose 1
131
36.5%
101
28.2%
101
28.2%
Any Myalgia - Dose 2
59
16.4%
60
16.8%
80
22.3%
Any Myalgia - Dose 3
77
21.4%
68
19%
72
20.1%
Any Myalgia - Across doses
166
46.2%
143
39.9%
136
38%
Grade 3 Myalgia - Dose 1
5
1.4%
3
0.8%
2
0.6%
Grade 3 Myalgia - Dose 2
2
0.6%
3
0.8%
2
0.6%
Grade 3 Myalgia - Dose 3
3
0.8%
4
1.1%
5
1.4%
Grade 3 Myalgia - Across doses
8
2.2%
8
2.2%
6
1.7%
Related Myalgia - Dose 1
91
25.3%
70
19.6%
67
18.7%
Related Myalgia - Dose 2
36
10%
40
11.2%
51
14.2%
Related Myalgia - Dose 3
50
13.9%
49
13.7%
46
12.8%
Related Myalgia - Across doses
128
35.7%
111
31%
100
27.9%
Any Rash - Dose 1
14
3.9%
7
2%
10
2.8%
Any Rash - Dose 2
10
2.8%
5
1.4%
8
2.2%
Any Rash - Dose 3
7
1.9%
5
1.4%
4
1.1%
Any Rash - Across doses
25
7%
16
4.5%
18
5%
Grade 3 Rash - Dose 1
0
0%
0
0%
0
0%
Grade 3 Rash - Dose 2
0
0%
0
0%
0
0%
Grade 3 Rash - Dose 3
0
0%
0
0%
0
0%
Grade 3 Rash - Across doses
0
0%
0
0%
0
0%
Related Rash - Dose 1
6
1.7%
5
1.4%
6
1.7%
Related Rash - Dose 2
6
1.7%
3
0.8%
4
1.1%
Related Rash - Dose 3
6
1.7%
3
0.8%
3
0.8%
Related Rash - Across doses
16
4.5%
10
2.8%
12
3.4%
Any Temperature ( ≥ 37.5°C) - Dose 1
19
5.3%
23
6.4%
18
5%
Any Temperature ( ≥ 37.5°C) - Dose 2
13
3.6%
21
5.9%
19
5.3%
Any Temperature ( ≥ 37.5°C) - Dose 3
32
8.9%
22
6.1%
22
6.1%
Any Temperature ( ≥ 37.5°C) - Across doses
53
14.8%
59
16.5%
47
13.1%
Grade 3 Temperature ( > 39.0°C) - Dose 1
2
0.6%
2
0.6%
2
0.6%
Grade 3 Temperature ( > 39.0°C) - Dose 2
0
0%
0
0%
2
0.6%
Grade 3 Temperature ( > 39.0°C) - Dose 3
6
1.7%
0
0%
0
0%
Grade 3 Temperature ( > 39.0°C) - Across doses
7
1.9%
2
0.6%
4
1.1%
Related Temperature - Dose 1
13
3.6%
11
3.1%
7
2%
Related Temperature - Dose 2
8
2.2%
9
2.5%
11
3.1%
Related Temperature - Dose 3
19
5.3%
12
3.4%
15
4.2%
Related Temperature - Across doses
35
9.7%
31
8.7%
30
8.4%
Any Urticaria - Dose 1
15
4.2%
7
2%
12
3.4%
Any Urticaria - Dose 2
8
2.2%
5
1.4%
12
3.4%
Any Urticaria - Dose 3
11
3.1%
4
1.1%
9
2.5%
Any Urticaria - Across doses
28
7.8%
13
3.6%
25
7%
Grade 3 Urticaria - Dose 1
2
0.6%
0
0%
0
0%
Grade 3 Urticaria - Dose 2
0
0%
1
0.3%
0
0%
Grade 3 Urticaria - Dose 3
2
0.6%
0
0%
0
0%
Grade 3 Urticaria - Across doses
4
1.1%
1
0.3%
0
0%
Related Urticaria - Dose 1
7
1.9%
6
1.7%
7
2%
Related Urticaria - Dose 2
5
1.4%
4
1.1%
4
1.1%
Related Urticaria - Dose 3
6
1.7%
4
1.1%
2
0.6%
Related Urticaria - Across doses
15
4.2%
11
3.1%
9
2.5%
15. Secondary Outcome
Title Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
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 was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.
Time Frame During the 30-day (from the day of vaccination up to 29 subsequent days) post-vaccination period

Outcome Measure Data

Analysis Population Description
The analysis was based on the TVC, which included all subjects with at least one study vaccine administered.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 359 358 358
Subjects with any AE(s)
91
25.3%
96
26.8%
101
28.2%
Subjects with any Grade 3 AE(s)
18
5%
8
2.2%
20
5.6%
Subjects with any Related AE(s)
8
2.2%
14
3.9%
15
4.2%
16. Secondary Outcome
Title Number of Subjects With Potentially Immune Mediated Diseases (pIMDs)
Description pIMDs were defined as a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
Time Frame From Day 0 up to Month 12

Outcome Measure Data

Analysis Population Description
The analysis was based on the TVC, which included all subjects with at least one study vaccine administered.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 359 358 358
Count of Participants [Participants]
3
0.8%
3
0.8%
0
0%
17. Secondary Outcome
Title Number of Subjects With Medically Significant Conditions (MSCs)
Description MSCs were defined as AEs prompting emergency room (ER) or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs not related to common diseases. Common diseases include: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.
Time Frame From Day 0 up to Month 36 (throughout the study period)

Outcome Measure Data

Analysis Population Description
The analysis was based on the TVC, which included all subjects with at least one study vaccine administered.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 359 358 358
Count of Participants [Participants]
77
21.4%
79
22.1%
63
17.6%
18. Secondary Outcome
Title Number of Subjects With Serious Adverse Events (SAEs)
Description SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.
Time Frame From Day 0 up to Month 36 (throughout the study period)

Outcome Measure Data

Analysis Population Description
The analysis was based on the TVC, which included all subjects with at least one study vaccine administered.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 359 358 358
Count of Participants [Participants]
21
5.8%
11
3.1%
14
3.9%
19. Secondary Outcome
Title Number of Subjects With SAEs Related to the Investigational Product, to Study Participation, to GSK Concomitant Products or Any Fatal SAE
Description SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. Related = an event assessed by the investigator as causally related to the investigational product, to study participation or to GSK concomitant products.
Time Frame From Day 0 up to Month 36 (throughout the study period)

Outcome Measure Data

Analysis Population Description
The analysis was based on the TVC, which included all subjects with at least one study vaccine administered.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 359 358 358
Related SAE(s)
0
0%
0
0%
0
0%
Fatal SAE(s)
0
0%
0
0%
1
0.3%
20. Secondary Outcome
Title Number of Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies
Description Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant congenital anomaly (CA), Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up and Pregnancy ongoing.
Time Frame From Day 0 up to Month 36 (throughout the study period)

Outcome Measure Data

Analysis Population Description
The analysis was based on the TVC, which included all subjects with the study vaccine administered and who reported any pregnancies and outcomes of reported pregnancies.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 0 0 1
Live infant NO ACA
0
0%
0
0%
0
0%
Live infant CA
0
0%
0
0%
0
0%
Elective termination NO ACA
0
0%
0
0%
1
0.3%
Elective termination CA
0
0%
0
0%
0
0%
Ectopic pregnancy
0
0%
0
0%
0
0%
Spontaneous abortion NO ACA
0
0%
0
0%
0
0%
Stillbirth NO ACA
0
0%
0
0%
0
0%
Stillbirth CA
0
0%
0
0%
0
0%
Lost to follow up
0
0%
0
0%
0
0%
Pregnancy ongoing
0
0%
0
0%
0
0%
Missing
0
0%
0
0%
0
0%
21. Secondary Outcome
Title Number of Subjects Using a Concomitant Medication Throughout the Study Period
Description The number of subjects who have used any concomitant medication, as well as any antipyretic, any prophylactic antipyretic and any antibiotic.
Time Frame From Day 0 up to Month 36 (throughout the study period) following vaccination after each dose and across doses

Outcome Measure Data

Analysis Population Description
The analysis was based on the TVC, which included all subjects with at least one study vaccine administered.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 359 358 358
Any, Dose 1
85
23.7%
87
24.3%
93
26%
Any antipyretic, Dose 1
51
14.2%
53
14.8%
47
13.1%
Prophylactic antipyretic, Dose 1
4
1.1%
0
0%
0
0%
Any antibiotic, Dose 1
15
4.2%
13
3.6%
23
6.4%
Prophylactic antibiotic, Dose 1
0
0%
0
0%
0
0%
Any, Dose 2
52
14.5%
55
15.4%
47
13.1%
Any antipyretic, Dose 2
32
8.9%
26
7.3%
29
8.1%
Prophylactic antipyretic, Dose 2
0
0%
1
0.3%
2
0.6%
Any antibiotic, Dose 2
8
2.2%
13
3.6%
12
3.4%
Prophylactic antibiotic, Dose 2
0
0%
0
0%
0
0%
Any, Dose 3
90
25.1%
83
23.2%
81
22.6%
Any antipyretic, Dose 3
48
13.4%
45
12.6%
38
10.6%
Prophylactic antipyretic, Dose 3
3
0.8%
1
0.3%
0
0%
Any antibiotic, Dose 3
28
7.8%
21
5.9%
24
6.7%
Prophylactic antibiotic, Dose 3
0
0%
0
0%
0
0%
Any, Across doses
171
47.6%
157
43.9%
161
45%
Any antipyretic, Across doses
110
30.6%
102
28.5%
95
26.5%
Prophylactic antipyretic, Across doses
5
1.4%
2
0.6%
2
0.6%
Any antibiotic, Across doses
48
13.4%
42
11.7%
50
14%
Prophylactic antibiotic, Across doses
0
0%
0
0%
0
0%
22. Secondary Outcome
Title Number of Subjects Completing the Vaccination Schedule
Description The number of subjects who have completed the three-dose vaccination schedule in all groups.
Time Frame From Day 0 up to Month 36 (throughout the study period)

Outcome Measure Data

Analysis Population Description
The analysis was based on the TVC, which included all subjects with at least one study vaccine administered.
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Measure Participants 359 358 358
Count of Participants [Participants]
351
97.8%
339
94.7%
346
96.6%

Adverse Events

Time Frame Solicited local and general symptoms: during the 7-day period after vaccination. Unsolicited AEs: during the 30-day period after vaccination. SAEs: throughout the study period (from Day 0 up to Month 36).
Adverse Event Reporting Description
Arm/Group Title Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Arm/Group Description Subjects who received 2 doses of Cervarix vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 2 doses of Gardasil vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm. Subjects who received 3 doses of Gardasil vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
All Cause Mortality
Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/359 (0%) 0/358 (0%) 1/358 (0.3%)
Serious Adverse Events
Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 21/359 (5.8%) 11/358 (3.1%) 14/358 (3.9%)
Blood and lymphatic system disorders
Lymphadenitis 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Ear and labyrinth disorders
Vertigo positional 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Gastrointestinal disorders
Abdominal pain 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Abdominal pain lower 0/359 (0%) 0 1/358 (0.3%) 1 0/358 (0%) 0
Colitis ulcerative 1/359 (0.3%) 1 0/358 (0%) 0 0/358 (0%) 0
Mouth cyst 0/359 (0%) 0 1/358 (0.3%) 1 0/358 (0%) 0
Immune system disorders
Anaphylactic reaction 1/359 (0.3%) 1 0/358 (0%) 0 0/358 (0%) 0
Anaphylactic shock 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Infections and infestations
Gastroenteritis 3/359 (0.8%) 3 0/358 (0%) 0 0/358 (0%) 0
Upper respiratory tract infection 2/359 (0.6%) 2 0/358 (0%) 0 1/358 (0.3%) 1
Appendicitis 1/359 (0.3%) 1 1/358 (0.3%) 1 0/358 (0%) 0
Pneumonia 1/359 (0.3%) 1 0/358 (0%) 0 1/358 (0.3%) 1
Epstein-Barr virus infection 1/359 (0.3%) 1 0/358 (0%) 0 0/358 (0%) 0
Gastroenteritis rotavirus 1/359 (0.3%) 1 0/358 (0%) 0 0/358 (0%) 0
Gastroenteritis viral 0/359 (0%) 0 1/358 (0.3%) 1 0/358 (0%) 0
Influenza 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Lung abscess 0/359 (0%) 0 1/358 (0.3%) 1 0/358 (0%) 0
Peritonitis 0/359 (0%) 0 1/358 (0.3%) 1 0/358 (0%) 0
Post procedural infection 1/359 (0.3%) 1 0/358 (0%) 0 0/358 (0%) 0
Tonsillitis 1/359 (0.3%) 1 0/358 (0%) 0 0/358 (0%) 0
Viral infection 0/359 (0%) 0 1/358 (0.3%) 1 0/358 (0%) 0
Injury, poisoning and procedural complications
Foot fracture 2/359 (0.6%) 2 0/358 (0%) 0 0/358 (0%) 0
Ankle fracture 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Contusion 1/359 (0.3%) 1 0/358 (0%) 0 0/358 (0%) 0
Forearm fracture 1/359 (0.3%) 1 0/358 (0%) 0 0/358 (0%) 0
Foreign body 1/359 (0.3%) 1 0/358 (0%) 0 0/358 (0%) 0
Joint dislocation 0/359 (0%) 0 1/358 (0.3%) 1 0/358 (0%) 0
Overdose 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Tendon injury 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Musculoskeletal and connective tissue disorders
Juvenile idiopathic arthritis 1/359 (0.3%) 1 0/358 (0%) 0 0/358 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Teratoma 0/359 (0%) 0 1/358 (0.3%) 1 0/358 (0%) 0
Nervous system disorders
Epilepsy 0/359 (0%) 0 1/358 (0.3%) 1 0/358 (0%) 0
Presyncope 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Seizure 0/359 (0%) 0 1/358 (0.3%) 1 0/358 (0%) 0
Syncope 1/359 (0.3%) 1 0/358 (0%) 0 0/358 (0%) 0
Tension headache 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous incomplete 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Psychiatric disorders
Completed suicide 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Depression 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Reproductive system and breast disorders
Menorrhagia 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Vulval ulceration 0/359 (0%) 0 0/358 (0%) 0 1/358 (0.3%) 1
Respiratory, thoracic and mediastinal disorders
Asthma 2/359 (0.6%) 2 1/358 (0.3%) 1 0/358 (0%) 0
Skin and subcutaneous tissue disorders
Eczema 0/359 (0%) 0 1/358 (0.3%) 1 0/358 (0%) 0
Erythema nodosum 1/359 (0.3%) 1 0/358 (0%) 0 0/358 (0%) 0
Vascular disorders
Orthostatic hypotension 1/359 (0.3%) 1 0/358 (0%) 0 0/358 (0%) 0
Other (Not Including Serious) Adverse Events
Cervarix 2 Dose Group Gardasil 2 Dose Group Gardasil 3 Dose Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 343/359 (95.5%) 321/358 (89.7%) 324/358 (90.5%)
Gastrointestinal disorders
Gastrointestinal disorder 55/359 (15.3%) 69 74/358 (20.7%) 103 70/358 (19.6%) 91
General disorders
Fatigue 192/359 (53.5%) 374 199/358 (55.6%) 359 193/358 (53.9%) 390
Pain 329/359 (91.6%) 784 277/358 (77.4%) 613 295/358 (82.4%) 669
Pyrexia 59/359 (16.4%) 70 64/358 (17.9%) 71 53/358 (14.8%) 65
Swelling 163/359 (45.4%) 288 98/358 (27.4%) 146 118/358 (33%) 200
Infections and infestations
Nasopharyngitis 8/359 (2.2%) 10 11/358 (3.1%) 12 20/358 (5.6%) 22
Upper respiratory tract infection 27/359 (7.5%) 31 29/358 (8.1%) 33 31/358 (8.7%) 34
Musculoskeletal and connective tissue disorders
Arthralgia 68/359 (18.9%) 98 82/358 (22.9%) 119 67/358 (18.7%) 108
Myalgia 166/359 (46.2%) 267 144/358 (40.2%) 230 136/358 (38%) 254
Nervous system disorders
Headache 149/359 (41.5%) 241 134/358 (37.4%) 213 152/358 (42.5%) 232
Skin and subcutaneous tissue disorders
Erythema 191/359 (53.2%) 370 135/358 (37.7%) 261 157/358 (43.9%) 288
Rash 26/359 (7.2%) 32 16/358 (4.5%) 17 18/358 (5%) 23
Urticaria 28/359 (7.8%) 36 13/358 (3.6%) 16 25/358 (7%) 33

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title GSK Response Center
Organization GlaxoSmithKline
Phone 866-435-7343
Email GSKClinicalSupportHD@gsk.com
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01462357
Other Study ID Numbers:
  • 115411
  • 2011-002035-26
First Posted:
Oct 31, 2011
Last Update Posted:
Nov 15, 2019
Last Verified:
Oct 1, 2019