Infections, Papillomavirus
Conditions
Keywords
HPV vaccine, cervical intraepithelial neoplasia (CIN), including new onset of autoimmune disease [NOAD]), new onset of chronic disease (NOCD), medically significant condition (MSC)
Brief summary
This extension study is conducted to assess the efficacy of the GSK 580299 vaccine against cervical intraepithelial neoplasia (CIN) lesions, cervical cancer and cytological abnormalities associated with human papillomavirus (HPV)-16 and/or HPV-18 or other oncogenic HPV types for an additional two years. All subjects who participated in the primary vaccination study NCT00316693 and who confirmed their interest in participating in a long term follow up study will therefore be invited to be followed for up to 48 months after administration of the first dose of vaccine. In addition, safety and persistence of the humoral immune response will be evaluated in this study. This protocol posting deals with objectives & outcome measures of the extension phase at Months 36 and 48. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00316693).
Interventions
PROCEDURELiquid-based cytology (LBC) sampling
LBC samples will be collected at Months 36 and 48 for cytology and HPV DNA testing (by PCR)
PROCEDUREBlood sampling
Blood samples will be collected at Months 36 and 48 for antibody determination
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 25 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that they can and will comply with the requirements of the protocol; * Written informed consent obtained from the subject prior to enrolment in the extension study; * A subject previously vaccinated in the NCT00316693 study. * Subjects who showed, at the last NCT00316693 study visit (at Month 24) willingness to participate in this extension study.
Exclusion criteria
* Use of any HPV vaccine other than the one administered in the NCT00316693 study; * Use of any investigational or non-registered product other than the study vaccine since last NCT00316693 study visit, or planned use during the study period; * 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; * Subjects who were diagnosed high grade or missing cytology at Month 0 in the NCT00316693 study; * Pregnant females and females who were pregnant less than 3 months ago.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Cases Associated With HPV16 and/or HPV18 Detected Within the Lesional Component of the Cervical Tissue Specimen. | From Month 0 up to Month 12 | Low-grade cervical lesions and higher lesions are defined as CIN1+, i.e. CIN grade 1 (CIN1), CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer (ICC). Detection of vaccine oncogenic Human papillomavirus (HPV) types 16 or 18 was made by polymerase chain reaction (PCR). For single type: Subjects Deoxyribonucleic acid (DNA) negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type. For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Incident Cervical Infection Associated With HPV-16 and/or 18. | From Month 0 up to Month 12 | For single type: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type. For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type. |
| Number of Subjects Reporting Cytological Abnormalities and Lesions Associated With HPV-16 and/or HPV-18. | From Month 0 up to Month 12 | Cytologically confirmed abnormalities and lesions (ASC-US+) are defined as atypical squamous cell of undetermined significance (ASC-US), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), atypical squamous cell-cannot exclude HSIL (ASC-H) and atypical glandular cells (AGC). For single type: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type. For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type. |
| Number of Subjects Reporting Cytologically Confirmed Abnormalities and Lesions Concurrently Associated With Any Oncogenic HPV Types. | From Month 0 up to Month 12 | Cytologically confirmed abnormalities and lesions (ASC-US+) are defined as ASC-US, LSIL, HSIL, ASC-H and AGC. HR= High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. |
| Number of Subjects Reporting Incident Cervical Infection With Any Oncogenic HPV Types. | From Month 0 up to Month 12 | HR=High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. |
| Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With HPV-16 and/or 18. | From Month 0 up to Month 12 | Persistent infection (12-month definition): detection of at least 2 positive HPV DNA PCR assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an approximate interval of 12 months (\>300 days). For single type: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type. For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type. |
| Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With Any Oncogenic HPV-types. | From Month 0 up to Month 12 | Persistent infection: subjects with at least 2 positive samples (difference \> than 300 days) and no negative samples in between. HR=High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. |
| Number of Subjects Reporting CIN1+ Associated With Any Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen. | From Month 0 up to Month 12 | Low-grade cervical lesions and higher lesions are defined as CIN1+, i.e. CIN1, CIN2, CIN3, AIS or ICC. HR=High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. |
| HPV-16 and HPV-18 Antibody Titers | At Month 0 and at Month 12 | Titers were expressed as Geometric Mean Titers (GMTs). Geometric mean titres were assessed by ELISA in the Cervarix Group. |
| Number of Subjects Reporting Serious Adverse Events (SAEs). | During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12 | SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. |
| Number of Subjects With New Onset of Chronic Diseases (NOCDs) Regardless of Causal Relationship to Vaccination and Intensity. | During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12 | NOCDs included autoimmune diseases, diabetes mellitus. |
| Number of Subjects With New Onset of Autoimmune Diseases (NOADs) Regardless of Causal Relationship to Vaccination and Intensity. | During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12 | — |
| Number of Subjects With Medically Significant Conditions (MSCs). | During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12 | MSCs were defined as adverse events (AEs) prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common disease. |
| Number of Subjects With Pregnancies and Pregnancy Outcomes. | During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12 (Month 48 Ext- NCT00316693). | Pregnancy outcomes are live infant, elective termination, ectopic pregnancy, stillbirth, spontaneous abortion, lost to follow-up and pregnancy ongoing. For each category it was specified if the infant presents congenital anomaly (CA) or no apparent congenital anomaly (No ACA). |
| Number of Subjects With HPV-16 and HPV-18 Antibodies Titers Equal to or Above the Assay Cut-off Values. | At Month 0 and at Month 12 | Assay cut-off values assessed were 8 Enzyme-linked Immunosorbent Assay (ELISA) units per millilitre (EL.U/mL) for HPV-16 antibodies and 7 ELISA units per millilitre (EL.U/mL) for HPV-18 antibodies in the Cervarix Group. |
Countries
Japan
Participant flow
Recruitment details
No vaccines were administered in this extension study. The mean duration of this study was aproximately 12 months for each subjects (from Month 0 up to Month 12). This study began 36 months after the first vaccination in study NCT00316693.
Pre-assignment details
Subjects were randomised in the primary vaccination study NCT00316693 to receive the Cervarix vaccine or the Aimmugen vaccine and were aged 20 - 25 years at the time of first vaccination. Only subjects showing willingness to participate in this long term follow-up study and who had signed the informed consent form entered this study.
Participants by arm
| Arm | Count |
|---|---|
| Cervarix Group subjects received 3 doses of Cervarix™ vaccine in primary vaccination study NCT00316693. | 375 |
| Aimmugen Group subjects received 3 doses of Aimmugen ™ vaccine in primary vaccination study NCT00316693. | 377 |
| Total | 752 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 8 | 12 |
| Overall Study | Other | 8 | 6 |
| Overall Study | Withdrawal by Subject | 1 | 11 |
Baseline characteristics
| Characteristic | Cervarix Group | Aimmugen Group | Total |
|---|---|---|---|
| Age, Continuous | 25.4 Years STANDARD_DEVIATION 1.72 | 25.5 Years STANDARD_DEVIATION 1.72 | 25.5 Years STANDARD_DEVIATION 1.72 |
| Sex: Female, Male Female | 375 Participants | 377 Participants | 752 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 11 / 375 | 16 / 377 |
Outcome results
Primary
Number of Subjects Reporting Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Cases Associated With HPV16 and/or HPV18 Detected Within the Lesional Component of the Cervical Tissue Specimen.
Low-grade cervical lesions and higher lesions are defined as CIN1+, i.e. CIN grade 1 (CIN1), CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer (ICC). Detection of vaccine oncogenic Human papillomavirus (HPV) types 16 or 18 was made by polymerase chain reaction (PCR). For single type: Subjects Deoxyribonucleic acid (DNA) negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type. For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type.
Time frame: From Month 0 up to Month 12
Population: The analysis was performed in subjects who were seronegative at baseline and negative for human papillomavirus (HPV) desoxyribonucleic acid (DNA) at baseline and Month 6 in the primary study (NCT00316693) for the HPV-type considered and for whom data concerning efficacy outcome measures were available in this follow-up study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Cases Associated With HPV16 and/or HPV18 Detected Within the Lesional Component of the Cervical Tissue Specimen. | CIN1+ HPV-16/18 (N=332;335) | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Cases Associated With HPV16 and/or HPV18 Detected Within the Lesional Component of the Cervical Tissue Specimen. | CIN1+ HPV-16 (N=286;289) | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Cases Associated With HPV16 and/or HPV18 Detected Within the Lesional Component of the Cervical Tissue Specimen. | CIN1+ HPV-18 (N=294;291) | 0 Subjects |
| Aimmugen Group | Number of Subjects Reporting Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Cases Associated With HPV16 and/or HPV18 Detected Within the Lesional Component of the Cervical Tissue Specimen. | CIN1+ HPV-16/18 (N=332;335) | 5 Subjects |
| Aimmugen Group | Number of Subjects Reporting Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Cases Associated With HPV16 and/or HPV18 Detected Within the Lesional Component of the Cervical Tissue Specimen. | CIN1+ HPV-16 (N=286;289) | 5 Subjects |
| Aimmugen Group | Number of Subjects Reporting Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Cases Associated With HPV16 and/or HPV18 Detected Within the Lesional Component of the Cervical Tissue Specimen. | CIN1+ HPV-18 (N=294;291) | 0 Subjects |
Secondary
HPV-16 and HPV-18 Antibody Titers
Titers were expressed as Geometric Mean Titers (GMTs). Geometric mean titres were assessed by ELISA in the Cervarix Group.
Time frame: At Month 0 and at Month 12
Population: The According-To-Protocol cohort for immunogenicity M48 EXT- NCT00316693 included all evaluable subjects for whom data concerning immunogenicity outcome measures were available in this current follow-up study for antibodies against at least one study vaccine antigen component.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | HPV-16 and HPV-18 Antibody Titers | HPV-16 [Month 0] (N=282) | 1409.9 Titers |
| Cervarix Group | HPV-16 and HPV-18 Antibody Titers | HPV-16 [Month 12] (N=291) | 1294.8 Titers |
| Cervarix Group | HPV-16 and HPV-18 Antibody Titers | HPV-18 [Month 0] (N=281) | 572.3 Titers |
| Cervarix Group | HPV-16 and HPV-18 Antibody Titers | HPV-18 [Month 12] (N=290) | 470.9 Titers |
Secondary
Number of Subjects Reporting CIN1+ Associated With Any Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen.
Low-grade cervical lesions and higher lesions are defined as CIN1+, i.e. CIN1, CIN2, CIN3, AIS or ICC. HR=High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Time frame: From Month 0 up to Month 12
Population: The analysis was performed in subjects who were DNA negative at baseline and Month 6 in the primary study (NCT00316693) for the HPV-type considered, regardless of their initial serostatus and for whom data concerning efficacy outcome measures were available in this current follow-up study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects Reporting CIN1+ Associated With Any Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen. | 8 Subjects |
| Aimmugen Group | Number of Subjects Reporting CIN1+ Associated With Any Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen. | 22 Subjects |
Secondary
Number of Subjects Reporting Cytological Abnormalities and Lesions Associated With HPV-16 and/or HPV-18.
Cytologically confirmed abnormalities and lesions (ASC-US+) are defined as atypical squamous cell of undetermined significance (ASC-US), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), atypical squamous cell-cannot exclude HSIL (ASC-H) and atypical glandular cells (AGC). For single type: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type. For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type.
Time frame: From Month 0 up to Month 12
Population: The analysis was performed in subjects who were seronegative at baseline and negative for HPV DNA at baseline and Month 6 in the primary study (NCT00316693) for the HPV-type considered and for whom data concerning efficacy outcome measures were available in this follow-up study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Cytological Abnormalities and Lesions Associated With HPV-16 and/or HPV-18. | ASC-US+ HPV-16/18 (N=332;335) | 3 Subjects |
| Cervarix Group | Number of Subjects Reporting Cytological Abnormalities and Lesions Associated With HPV-16 and/or HPV-18. | ASC-US+ HPV-16 (N=286;289) | 2 Subjects |
| Cervarix Group | Number of Subjects Reporting Cytological Abnormalities and Lesions Associated With HPV-16 and/or HPV-18. | ASC-US+ HPV-18 (N=294;291) | 1 Subjects |
| Aimmugen Group | Number of Subjects Reporting Cytological Abnormalities and Lesions Associated With HPV-16 and/or HPV-18. | ASC-US+ HPV-16/18 (N=332;335) | 11 Subjects |
| Aimmugen Group | Number of Subjects Reporting Cytological Abnormalities and Lesions Associated With HPV-16 and/or HPV-18. | ASC-US+ HPV-16 (N=286;289) | 10 Subjects |
| Aimmugen Group | Number of Subjects Reporting Cytological Abnormalities and Lesions Associated With HPV-16 and/or HPV-18. | ASC-US+ HPV-18 (N=294;291) | 2 Subjects |
Secondary
Number of Subjects Reporting Cytologically Confirmed Abnormalities and Lesions Concurrently Associated With Any Oncogenic HPV Types.
Cytologically confirmed abnormalities and lesions (ASC-US+) are defined as ASC-US, LSIL, HSIL, ASC-H and AGC. HR= High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Time frame: From Month 0 up to Month 12
Population: The analysis was performed in subjects who were DNA negative at baseline and Month 6 in the primary study (NCT00316693) for the HPV-type considered, regardless of their initial serostatus and for whom data concerning efficacy outcome measures were available in this current follow-up study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects Reporting Cytologically Confirmed Abnormalities and Lesions Concurrently Associated With Any Oncogenic HPV Types. | 33 Subjects |
| Aimmugen Group | Number of Subjects Reporting Cytologically Confirmed Abnormalities and Lesions Concurrently Associated With Any Oncogenic HPV Types. | 45 Subjects |
Secondary
Number of Subjects Reporting Incident Cervical Infection Associated With HPV-16 and/or 18.
For single type: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type. For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type.
Time frame: From Month 0 up to Month 12
Population: The analysis was performed in subjects who were seronegative at baseline and negative for HPV DNA at baseline and Month 6 in the primary study (NCT00316693) for the HPV-type considered and for whom data concerning efficacy outcome measures were available in this follow-up study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Incident Cervical Infection Associated With HPV-16 and/or 18. | Incident infection HPV-16/18 (N=332;335) | 7 Subjects |
| Cervarix Group | Number of Subjects Reporting Incident Cervical Infection Associated With HPV-16 and/or 18. | Incident infection HPV-16 (N=286;289) | 3 Subjects |
| Cervarix Group | Number of Subjects Reporting Incident Cervical Infection Associated With HPV-16 and/or 18. | Incident infection HPV-18 (N=294;291) | 5 Subjects |
| Aimmugen Group | Number of Subjects Reporting Incident Cervical Infection Associated With HPV-16 and/or 18. | Incident infection HPV-16/18 (N=332;335) | 28 Subjects |
| Aimmugen Group | Number of Subjects Reporting Incident Cervical Infection Associated With HPV-16 and/or 18. | Incident infection HPV-16 (N=286;289) | 16 Subjects |
| Aimmugen Group | Number of Subjects Reporting Incident Cervical Infection Associated With HPV-16 and/or 18. | Incident infection HPV-18 (N=294;291) | 13 Subjects |
Secondary
Number of Subjects Reporting Incident Cervical Infection With Any Oncogenic HPV Types.
HR=High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Time frame: From Month 0 up to Month 12
Population: The analysis was performed in subjects who were negative for HPV DNA at baseline and Month 6 in the primary study (NCT00316693) for the HPV-type considered, regardless of their initial serostatus and for whom data concerning efficacy outcome measures were available in this current follow-up study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects Reporting Incident Cervical Infection With Any Oncogenic HPV Types. | 87 Subjects |
| Aimmugen Group | Number of Subjects Reporting Incident Cervical Infection With Any Oncogenic HPV Types. | 98 Subjects |
Secondary
Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With Any Oncogenic HPV-types.
Persistent infection: subjects with at least 2 positive samples (difference \> than 300 days) and no negative samples in between. HR=High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Time frame: From Month 0 up to Month 12
Population: The analysis was performed in subjects who were negative for HPV DNA at baseline and Month 6 in the primary study (NCT00316693) for the HPV-type considered, regardless of their initial serostatus and for whom data concerning efficacy outcome measures were available in this current follow-up study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With Any Oncogenic HPV-types. | 19 Subjects |
| Aimmugen Group | Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With Any Oncogenic HPV-types. | 31 Subjects |
Secondary
Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With HPV-16 and/or 18.
Persistent infection (12-month definition): detection of at least 2 positive HPV DNA PCR assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an approximate interval of 12 months (\>300 days). For single type: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type. For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type.
Time frame: From Month 0 up to Month 12
Population: The analysis was performed in subjects who were seronegative at baseline and negative for HPV DNA at baseline and Month 6 in the primary study (NCT00316693) for the HPV-type considered and for whom data concerning efficacy outcome measures were available in this follow-up study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With HPV-16 and/or 18. | Persistent infection HPV-16/18 (N=257;241) | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With HPV-16 and/or 18. | Persistent infection HPV-16 (N=225;206) | 0 Subjects |
| Cervarix Group | Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With HPV-16 and/or 18. | Persistent infection HPV-18 (N=227;209) | 0 Subjects |
| Aimmugen Group | Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With HPV-16 and/or 18. | Persistent infection HPV-16/18 (N=257;241) | 9 Subjects |
| Aimmugen Group | Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With HPV-16 and/or 18. | Persistent infection HPV-16 (N=225;206) | 6 Subjects |
| Aimmugen Group | Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With HPV-16 and/or 18. | Persistent infection HPV-18 (N=227;209) | 4 Subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs).
SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.
Time frame: During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12
Population: The analysis was performed on all subjects from the Total Vaccinated cohort who came for the current follow-up study and for whom data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects Reporting Serious Adverse Events (SAEs). | 11 Subjects |
| Aimmugen Group | Number of Subjects Reporting Serious Adverse Events (SAEs). | 16 Subjects |
Secondary
Number of Subjects With HPV-16 and HPV-18 Antibodies Titers Equal to or Above the Assay Cut-off Values.
Assay cut-off values assessed were 8 Enzyme-linked Immunosorbent Assay (ELISA) units per millilitre (EL.U/mL) for HPV-16 antibodies and 7 ELISA units per millilitre (EL.U/mL) for HPV-18 antibodies in the Cervarix Group.
Time frame: At Month 0 and at Month 12
Population: The According-To-Protocol cohort for immunogenicity included all evaluable subjects for whom data concerning immunogenicity outcome measures were available in this current follow-up study for antibodies against at least one study vaccine antigen component.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Subjects With HPV-16 and HPV-18 Antibodies Titers Equal to or Above the Assay Cut-off Values. | HPV-18 >=7 EL.U/mL [at Month 0] (N=281) | 281 Subjects |
| Cervarix Group | Number of Subjects With HPV-16 and HPV-18 Antibodies Titers Equal to or Above the Assay Cut-off Values. | HPV-16 >=8 EL.U/mL [at Month 0] (N=282) | 282 Subjects |
| Cervarix Group | Number of Subjects With HPV-16 and HPV-18 Antibodies Titers Equal to or Above the Assay Cut-off Values. | HPV-16 >=8 EL.U/mL [at Month 12] (N=291) | 291 Subjects |
| Cervarix Group | Number of Subjects With HPV-16 and HPV-18 Antibodies Titers Equal to or Above the Assay Cut-off Values. | HPV-18 >=7 EL.U/mL [at Month 12] (N=290) | 290 Subjects |
Secondary
Number of Subjects With Medically Significant Conditions (MSCs).
MSCs were defined as adverse events (AEs) prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common disease.
Time frame: During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12
Population: The analysis was performed on all subjects from the Total Vaccinated cohort who came for the current follow-up study and for whom data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects With Medically Significant Conditions (MSCs). | 11 Subjects |
| Aimmugen Group | Number of Subjects With Medically Significant Conditions (MSCs). | 15 Subjects |
Secondary
Number of Subjects With New Onset of Autoimmune Diseases (NOADs) Regardless of Causal Relationship to Vaccination and Intensity.
Time frame: During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12
Population: The analysis was performed on all subjects from the Total Vaccinated cohort who came for the current follow-up study and for whom data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects With New Onset of Autoimmune Diseases (NOADs) Regardless of Causal Relationship to Vaccination and Intensity. | 2 Subjects |
| Aimmugen Group | Number of Subjects With New Onset of Autoimmune Diseases (NOADs) Regardless of Causal Relationship to Vaccination and Intensity. | 1 Subjects |
Secondary
Number of Subjects With New Onset of Chronic Diseases (NOCDs) Regardless of Causal Relationship to Vaccination and Intensity.
NOCDs included autoimmune diseases, diabetes mellitus.
Time frame: During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12
Population: The analysis was performed on all subjects from the Total Vaccinated cohort who came for the current follow-up study and for whom data were available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cervarix Group | Number of Subjects With New Onset of Chronic Diseases (NOCDs) Regardless of Causal Relationship to Vaccination and Intensity. | 2 Subjects |
| Aimmugen Group | Number of Subjects With New Onset of Chronic Diseases (NOCDs) Regardless of Causal Relationship to Vaccination and Intensity. | 2 Subjects |
Secondary
Number of Subjects With Pregnancies and Pregnancy Outcomes.
Pregnancy outcomes are live infant, elective termination, ectopic pregnancy, stillbirth, spontaneous abortion, lost to follow-up and pregnancy ongoing. For each category it was specified if the infant presents congenital anomaly (CA) or no apparent congenital anomaly (No ACA).
Time frame: During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12 (Month 48 Ext- NCT00316693).
Population: The analysis was performed on all subjects from the Total Vaccinated cohort who came for the current follow-up study and for whom data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Live infant CA | 0 Subjects |
| Cervarix Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Live infant No ACA | 28 Subjects |
| Cervarix Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Elective termination No ACA | 4 Subjects |
| Cervarix Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Spontaneous abortion No ACA | 3 Subjects |
| Cervarix Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Stillbirth No ACA | 1 Subjects |
| Cervarix Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Ectopic pregnancy | 0 Subjects |
| Cervarix Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Lost to follow-up | 0 Subjects |
| Cervarix Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Pregnancy ongoing | 1 Subjects |
| Aimmugen Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Pregnancy ongoing | 0 Subjects |
| Aimmugen Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Stillbirth No ACA | 0 Subjects |
| Aimmugen Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Live infant No ACA | 30 Subjects |
| Aimmugen Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Live infant CA | 1 Subjects |
| Aimmugen Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Lost to follow-up | 2 Subjects |
| Aimmugen Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Elective termination No ACA | 3 Subjects |
| Aimmugen Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Ectopic pregnancy | 1 Subjects |
| Aimmugen Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Spontaneous abortion No ACA | 4 Subjects |