Infections, Papillomavirus, Papillomavirus Vaccines
Conditions
Keywords
HPV vaccine, cervical cancer
Brief summary
Infection with human papillomavirus (HPV) has been clearly established as the necessary cause of cervical cancer. This study is designed to evaluate the long-term immunogenicity and safety of the 580299 HPV vaccine up to 10 years after administration of the first dose of HPV vaccine (Month 0) administered in the primary study 580299/013. This protocol posting deals with objectives & outcome measures of the extension phase from Month 60 to Month 120. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT00196924). The objectives & outcome measures of the extension phase up to Month 48 are presented in a separate protocol posting (NCT00316706).
Detailed description
Subjects were aged 10-14 years at the time of entry into the primary study. No vaccine will be administered in this extension study. Results on outcome measures describing analyses on other studies are not reported in this record. Please refer to the records mentioned in the respective outcome measure titles.
Interventions
PROCEDUREBlood sampling
Blood samples were to be collected at Months 60, 72, 84, 96, 108 and 120
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
15 Years to 24 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that they and/or their parents or legally acceptable representative (LAR) can and will comply with the requirements of the protocol should be enrolled in the study. * A female enrolled in the immunogenicity subset of study 580299-013, who received three doses of HPV vaccine and participated in the extension study of 580299-013. * Written informed assent obtained from the subject. For subjects below the legal age of consent, written informed consent must be obtained from a parent or legally acceptable representative of the subject.
Exclusion criteria
* 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. * Use of any investigational or non-registered product (drug or vaccine) or planned use during the study period. * Administration or planned administration of any HPV vaccine, other than the vaccine administered in study 580299-013. * Chronic administration of immunosuppressants or other immune-modifying drugs occurring within the three months preceding study entry. * Administration of immunoglobulins and/or any blood products occurring within the three months preceding study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values. | At Month 60 | Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer \< 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer \>= 8 or 7 EL.U/mL prior to vaccination. |
| Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers | At Month 60 | Anti-HPV-16 and 18 antibody titers are given in Geometric Mean Titers (GMTs) in Enzyme-linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Serious Adverse Events (SAEs) | From Month 48 to Month 60 | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. |
Countries
Colombia, Germany, Honduras, Panama, Taiwan
Participant flow
Recruitment details
Subjects who participated in the primary study (NCT00196924) and received 3 doses of Cervarix.
Pre-assignment details
Subjects enrolled in this study were primed with Cervarix vaccine as part of study NCT00196924. Subjects not returning for a specific visit were not withdrawn and could participate in the subsequent follow-up phases. Actual enrollment differed depending on the rate of return for the follow-up study, so not all subjects enrolled came to each visit.
Participants by arm
| Arm | Count |
|---|---|
| Cervarix Group Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule. | 529 |
| Total | 529 |
Baseline characteristics
| Characteristic | Cervarix Group |
|---|---|
| Age, Continuous Year 10 | 22.0 Years STANDARD_DEVIATION 1.4 |
| Age, Continuous Year 5 | 17.1 Years STANDARD_DEVIATION 1.4 |
| Age, Continuous Year 6 | 18.0 Years STANDARD_DEVIATION 1.4 |
| Age, Continuous Year 7 | 19.0 Years STANDARD_DEVIATION 1.39 |
| Age, Continuous Year 8 | 20.0 Years STANDARD_DEVIATION 1.4 |
| Age, Continuous Year 9 | 21.1 Years STANDARD_DEVIATION 1.42 |
| Sex: Female, Male Female | 529 Participants |
| Sex: Female, Male Male | 0 Participants |
| Sex/Gender, Customized Female | 522 Participants |
| Sex/Gender, Customized Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 9 / 397 | 20 / 529 | 20 / 523 | 8 / 522 | 15 / 507 | 6 / 495 |
Outcome results
Primary
Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers
Anti-HPV-16 and 18 antibody titers are given in Geometric Mean Titers (GMTs) in Enzyme-linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).
Time frame: At month 72
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity Month 72 which included all evaluable subjects from the primary study (NCT00196924) for whom serology results were available at the Month 72 blood sampling timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers | anti-HPV-16 Month 72 [N=502] | 1973.9 EL.U/mL |
| Cervarix Group | Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers | anti-HPV-18 Month 72 [N=502] | 762.8 EL.U/mL |
Primary
Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers
Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer \< 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer \>= 8 or 7 EL.U/mL prior to vaccination.
Time frame: At Month 120
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity Month 120 which included all evaluable subjects from the primary study (NCT00196924) for whom serology results were available at the Month 120 blood sampling timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers | Anti-HPV-16 Month 120 [N=416] | 1607.9 EL.U/mL |
| Cervarix Group | Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers | Anti-HPV-18 Month 120 [N=415] | 608 EL.U/mL |
Primary
Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers
Anti-HPV-16 and 18 antibody titers are given in Geometric Mean Titers (GMTs) in Enzyme-linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).
Time frame: At Month 84
Population: The analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity Month 84 which included all evaluable subjects from the primary study (NCT00196924) for whom serology results were available at the Month 84 blood sampling timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers | anti-HPV-016 Month 84 [N=494] | 1756.7 EL.U/mL |
| Cervarix Group | Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers | anti-HPV-018 Month 84 [N=494] | 609.7 EL.U/mL |
Primary
Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers
Anti-HPV-16 and 18 antibody titers are given in Geometric Mean Titers (GMTs) in Enzyme-linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).
Time frame: At Month 96
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity Month 96 which included all evaluable subjects from the primary study (NCT00196924) for whom serology results were available at the Month 96 blood sampling timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers | anti-HPV-16 Month 96 [N=499] | 1671.0 EL.U/mL |
| Cervarix Group | Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers | anti-HPV-18 Month 96 [N=499] | 679.0 EL.U/mL |
Primary
Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers
Anti-HPV-16 and 18 antibody titers are given in Geometric Mean Titers (GMTs) in Enzyme-linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).
Time frame: At Month 60
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity Month 60 which included all evaluable subjects from the primary study (NCT00196924) for whom serology results were available at the Month 60 blood sampling timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers | anti-HPV-16 Month 60 [N=376] | 2262.9 EL.U/mL |
| Cervarix Group | Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers | anti-HPV-18 Month 60 [N=376] | 778.6 EL.U/mL |
Primary
Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers
Anti-HPV-16 and 18 antibody titers are given in Geometric Mean Titers (GMTs) in Enzyme-linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).
Time frame: At Month 108
Population: The analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity Month 108 which included all evaluable subjects from the primary study (NCT00196924) for whom serology results were available at the Month 108 blood sampling timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers | Anti-HPV-16 Month 108 [N=392] | 1946.5 EL.U/ML |
| Cervarix Group | Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers | Anti-HPV-18 Month 108 [N=391] | 754.0 EL.U/ML |
Primary
Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values.
Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer \< 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer \>= 8 or 7 EL.U/mL prior to vaccination.
Time frame: At Month 60
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity Month 60 which included all evaluable subjects from the primary study (NCT00196924) for whom serology results were available at the Month 60 blood sampling timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values. | anti-HPV-16 Month 60 [N=353] | 353 Subjects |
| Cervarix Group | Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values. | anti-HPV-18 Month 60 [N=358] | 358 Subjects |
Primary
Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values.
Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer \< 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer \>= 8 or 7 EL.U/mL prior to vaccination.
Time frame: At Month 72
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity Month 72 which included all evaluable subjects from the primary study (NCT00196924) for whom serology results were available at the Month 72 blood sampling timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values. | anti-HPV-16 Month 72 [N=475] | 475 Subjects |
| Cervarix Group | Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values. | anti-HPV-18 Month 72 [N=478] | 478 Subjects |
Primary
Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values.
Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer \< 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer \>= 8 or 7 EL.U/mL prior to vaccination.
Time frame: At Month 84
Population: The analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity Month 84 which included all evaluable subjects from the primary study (NCT00196924) for whom serology results were available at the Month 84 blood sampling timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values. | HPV-18 Month 84 [N=473] | 473 Subjects |
| Cervarix Group | Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values. | HPV-16 Month 84 [N=469] | 469 Subjects |
Primary
Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values.
Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer \< 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer \>= 8 or 7 EL.U/mL prior to vaccination.
Time frame: At Month 96
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity Month 96 which included all evaluable subjects from the primary study (NCT00196924) for whom serology results were available at the Month 96 blood sampling timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values. | anti-HPV-16 Month 96 [N=473] | 473 Subjects |
| Cervarix Group | Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values. | anti-HPV-18 Month 96 [N=477] | 477 Subjects |
Primary
Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values.
Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer \< 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer \>= 8 or 7 EL.U/mL prior to vaccination.
Time frame: At Month 120
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity Month 120 which included all evaluable subjects from the primary study (NCT00196924) for whom serology results were available at the Month 120 blood sampling timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values. | Anti-HPV-18 Month 120 [N=395] | 395 Subjects |
| Cervarix Group | Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values. | Anti-HPV-16 Month 120 [N=393] | 393 Subjects |
Primary
Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values.
Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer \< 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer \>= 8 or 7 EL.U/mL prior to vaccination.
Time frame: At Month 108
Population: Analysis was performed on the According-To-Protocol (ATP) cohort for immunogenicity Month 108 which included all evaluable subjects from the primary study (NCT00196924) for whom serology results were available at the Month 108 blood sampling timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values. | Anti-HPV-16 Month 108 [N=374] | 372 Subjects |
| Cervarix Group | Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values. | Anti-HPV-18 Month 108 [N=370] | 368 Subjects |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: From Month 48 to Month 60
Population: The analysis was performed on the Month 60 Total Vaccinated cohort, which included all vaccinated subjects (who had received 3 doses during the primary study (NCT00196924)) for whom data were available for the Month 60 time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects With Serious Adverse Events (SAEs) | 9 Subjects |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: From Month 60 to Month 72
Population: Analysis was performed on the Month 72 Total Vaccinated cohort, which included all vaccinated subjects (who had received 3 doses during the primary study (NCT00196924)) for whom data were available for the Month 72 time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects With Serious Adverse Events (SAEs) | 20 Subjects |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: From Month 72 to Month 84
Population: Analysis was performed on the Month 84 Total Vaccinated cohort, which included all vaccinated subjects (who had received 3 doses during the primary study (NCT00196924)) for whom data were available for the Month 84 time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects With Serious Adverse Events (SAEs) | 20 Subjects |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: From Month 84 to Month 96
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects With Serious Adverse Events (SAEs) | 8 Subjects |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: From Month 96 to Month 108
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects With Serious Adverse Events (SAEs) | 15 Subjects |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: From Month 108 to Month 120
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects With Serious Adverse Events (SAEs) | 6 Subjects |