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

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)

Population: 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.

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)

Population: 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.

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)

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: 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.

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)

Population: The analysis was based on the TVC, which included all subjects with at least one study vaccine administered.

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)

Population: 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.

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

Population: The analysis was based on the TVC, which included all subjects with at least one study vaccine administered.

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

Population: 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.

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

Population: 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.

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

Population: The analysis was based on the TVC, which included all subjects with at least one study vaccine administered.

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)

Population: The analysis was based on the TVC, which included all subjects with at least one study vaccine administered.

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

Population: The analysis was based on the TVC, which included all subjects with at least one study vaccine administered.

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)

Population: The analysis was based on the TVC, which included all subjects with at least one study vaccine administered.

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)

Population: The analysis was based on the TVC, which included all subjects with at least one study vaccine administered.

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

Population: 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.