Infections, Papillomavirus
Conditions
Keywords
Human papillomavirus infection,, cervical cancer, HPV vaccine,
Brief summary
Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. Vaccination of pre-teens and adolescents, ideally before sexual debut and thus before exposure to oncogenic HPV, is a rational strategy for prevention of cervical cancer, and so HPV vaccination could complement the existing pre-adolescent/adolescent vaccination programs. Therefore, this Phase IIIb study is designed to evaluate the safety and immunogenicity of co-administering a commercially available vaccine with GSK Biologicals' HPV-16/18 L1 AS04 (Cervarix ®) vaccine as compared to the administration of either vaccine alone. This Protocol Posting has been updated in order to comply with the FDA AA, Sept 2007.
Interventions
BIOLOGICALCervarix™
Three doses of vaccine administered intramuscularly with the second and third dose given one month and six months after the first dose
BIOLOGICALTwinrix ™ Paediatric
Three doses of vaccine administered intramuscularly with the second and third dose given one month and six months after the first dose
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
9 Years to 15 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that they and/or their legally acceptable representatives (LARs) can and will comply with the requirements of the protocol should be enrolled in the study. * A female between, and including, 9 and 15 years of age (has not attained her 16th birthday) at the time of the first vaccination. * Written informed consent obtained from the subject prior to enrolment. For subjects below the legal age of consent, written informed consent must be obtained from the subject's LAR, and written informed assent must be obtained from the subject. * Healthy subjects as established by medical history and clinical examination before entering into the study. * Subjects must not be pregnant. * Subjects must be of non-childbearing potential, or if the subject is of childbearing potential, she must be abstinent or use adequate contraception for 30 days prior to vaccination and must agree to continue such precautions for two months after completion of the vaccination series.
Exclusion criteria
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 12). * Concurrently participating in another clinical study, at any time during the study period (up to the Month 12 telephone contact), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). * Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. * Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after each dose of vaccine(s). Administration of routine vaccines may be allowed up to 8 days before the first dose * A subject planning to become pregnant, likely to become pregnant or planning to discontinue contraceptive precautions during the study period and up to two months after the last vaccine dose. * Pregnant or breastfeeding women. * Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period. * Previous administration of components of the investigational vaccine. * Previous vaccination against hepatitis A or B planned administration of any hepatitis A or B vaccine other than that foreseen by the study protocol during the study period. * History of hepatitis A or B infection. * Known exposure to hepatitis A or B within the previous 6 weeks. * Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests. * Cancer or autoimmune disease under treatment. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccines * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination * Acute disease at the time of enrolment. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Seroconverted for Anti-hepatitis A (Anti-HAV) Antibodies | At Month 7 | Seroconversion is defined as the appearance of anti-HAV antibodies \[i.e., antibody titer greater than or equal to 15 milli-international units/milliliter (mIU/mL)\] in the sera of subjects seronegative (antibody titer below 15 mIU/mL) before vaccination. |
| Anti-Heptatis A (HAV) Antibody Titers. | At Month 7 | Titers are given as Geometric Mean Titers (GMTs) expressed as mIU/mL. |
| Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies | At Month 7 | A subject seroprotected against HBs is a subject with antibody titers greater than or equal to 10 mIU/mL. |
| Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | At Month 7 | Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values = 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies. |
| Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers | At Month 7 | Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-HAV Antibody Titers | One month after the second dose of vaccine | Titers are given as geometric mean titers (GMTs) expressed as mIU/mL. |
| Number of Subjects Seroconverted and Number of Subjects Seroprotected for Anti-HBs Antibodies | One month after the second dose of vaccine | Seroconversion is defined as the appearance of anti-HBs antibodies (i.e., antibody titer greater than or equal to 3.3 mIU/mL) in the sera of subjects seronegative (with antibody titers below 3.3 mIU/mL) before vaccination. A seroprotected subject against HBs is a subject with antibody titers greater than or equal to 10 mIU/mL. |
| Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | One month after the second dose of vaccine | Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values assessed include 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies. |
| Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers | One month after the second dose of vaccine | Titers are given as Geometric Mean Titers (GMTs) expressed as EL.U/mL. |
| Anti-HBs Antibody Titers | At Month 7 | Titers are given as Geometric Mean Titers (GMTs)expressed as mIU/mL. |
| Number of Subjects Reporting Solicited General Symptoms | During the 7-day period following vaccination | Solicited general symptoms assessed include arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, temperature \[axillary route, greater than or equal to 37.5 degree Celsius (°C)\] and urticaria. |
| Number of Subjects Reporting Medically Significant Conditions | Throughout the active phase of the study (up to Month 7) | Medically significant conditions include adverse events (AEs) prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury. |
| Number of Subjects Reporting Unsolicited Adverse Events | During the 30-day period following any vaccination | Unsolicited adverse events include any adverse event 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. |
| Number of Subjects Reporting Serious Adverse Events (SAE) | Throughout the study (up to Month 12) | 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. |
| Number of Subjects Reporting Solicited Local Symptoms | During the 7-day period (Day 0-6) following vaccination | Solicited local symptoms assessed include injection site pain, redness and swelling. Data are presented across doses. |
| Number of Subjects Seroconverted for Anti-HBs Antibodies | At month 7 | Seroconversion is defined as the appearance of anti-HBs antibodies (i.e., antibody titer greater than or equal to 3.3 mIU/mL) in the sera of subjects seronegative (with antibody titers below 3.3 mIU/mL) before vaccination. |
| Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies in Vaccine Recipients Aged 9 Years | At Month 7 | Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values = 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies. |
| Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers in Vaccine Recipients Aged 9 Years | At Month 7 | Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL). |
| Number of Subjects Seroconverted for Anti-HAV Antibodies | One month after the second dose of vaccine | Seroconversion is defined as the appearance of anti-HAV antibodies (i.e., antibody titer greater than or equal to 15 mIU/mL) in the sera of subjects seronegative (antibody titer below 15 mIU/mL) before vaccination. |
Countries
Canada, Denmark, Hungary, Sweden
Participant flow
Pre-assignment details
Although the total number of enrolled subjects for this study was 814, one subject did not receive any study vaccine and was therefore not considered as started in the 'Participant Flow' section.
Participants by arm
| Arm | Count |
|---|---|
| Cervarix™ & Twinrix™ Group Subjects received 3 doses of Human Papilloma Virus (HPV) vaccine co-administered with combined Hepatitis A & Hepatitis B (HAB) vaccine (Months 0, 1 & 6). | 272 |
| Cervarix™ Group Subjects received 3 doses of HPV vaccine (Months 0, 1 & 6). | 270 |
| Twinrix™ Group Subjects received 3 doses of HAB vaccine (Months 0, 1 & 6). | 271 |
| Total | 813 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 1 | 3 |
Baseline characteristics
| Characteristic | Cervarix™ & Twinrix™ Group | Cervarix™ Group | Twinrix™ Group | Total |
|---|---|---|---|---|
| Age, Continuous | 11.2 years STANDARD_DEVIATION 2.04 | 11.2 years STANDARD_DEVIATION 2.02 | 11.2 years STANDARD_DEVIATION 1.99 | 11.2 years STANDARD_DEVIATION 2.01 |
| Sex: Female, Male Female | 272 Participants | 270 Participants | 271 Participants | 813 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 258 / 272 | 256 / 270 | 224 / 271 |
| serious Total, serious adverse events | 2 / 272 | 4 / 270 | 4 / 271 |
Outcome results
Primary
Anti-Heptatis A (HAV) Antibody Titers.
Titers are given as Geometric Mean Titers (GMTs) expressed as mIU/mL.
Time frame: At Month 7
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity, in subjects seronegative for anti-HAV before vaccination (i.e. with antibody titer below 15 mIU/mL).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cervarix™ & Twinrix™ Group | Anti-Heptatis A (HAV) Antibody Titers. | 4504.2 mIU/mL |
| Twinrix™ Group | Anti-Heptatis A (HAV) Antibody Titers. | 5288.4 mIU/mL |
Primary
Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers
Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).
Time frame: At Month 7
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity, in subjects seronegative for the corresponding HPV type before vaccination, i.e. with antibody titers below 8 EL.U/mL for anti-HPV-16 antibodies and below 7 EL.U/mL for anti-HPV-18 antibodies.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix™ & Twinrix™ Group | Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers | Anti-HPV-16 GMTs | 22993.5 EL.U/mL |
| Cervarix™ & Twinrix™ Group | Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers | Anti-HPV-18 GMTs | 8671.2 EL.U/mL |
| Cervarix™ Group | Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers | Anti-HPV-16 GMTs | 26981.9 EL.U/mL |
| Cervarix™ Group | Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers | Anti-HPV-18 GMTs | 11182.7 EL.U/mL |
Primary
Number of Subjects Seroconverted for Anti-hepatitis A (Anti-HAV) Antibodies
Seroconversion is defined as the appearance of anti-HAV antibodies \[i.e., antibody titer greater than or equal to 15 milli-international units/milliliter (mIU/mL)\] in the sera of subjects seronegative (antibody titer below 15 mIU/mL) before vaccination.
Time frame: At Month 7
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity, in subjects seronegative for anti-HAV before vaccination (i.e. with antibody titer below 15 mIU/mL).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix™ & Twinrix™ Group | Number of Subjects Seroconverted for Anti-hepatitis A (Anti-HAV) Antibodies | 240 Participants |
| Twinrix™ Group | Number of Subjects Seroconverted for Anti-hepatitis A (Anti-HAV) Antibodies | 242 Participants |
Primary
Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies
Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values = 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.
Time frame: At Month 7
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity, in subjects seronegative for the corresponding HPV type before vaccination, i.e. with antibody titers below 8 EL.U/mL for anti-HPV-16 antibodies and below 7 EL.U/mL for anti-HPV-18 antibodies.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix™ & Twinrix™ Group | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-16 | 228 Participants |
| Cervarix™ & Twinrix™ Group | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-18 | 238 Participants |
| Cervarix™ Group | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-16 | 233 Participants |
| Cervarix™ Group | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-18 | 241 Participants |
Primary
Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies
A subject seroprotected against HBs is a subject with antibody titers greater than or equal to 10 mIU/mL.
Time frame: At Month 7
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity, in subjects seronegative for anti-HBs before vaccination, i.e. with anti-HBs antibody titer greater than or equal to 3.3 mIU/mL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix™ & Twinrix™ Group | Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies | 175 Participants |
| Twinrix™ Group | Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies | 161 Participants |
Secondary
Anti-HAV Antibody Titers
Titers are given as geometric mean titers (GMTs) expressed as mIU/mL.
Time frame: One month after the second dose of vaccine
Population: Analysis was performed on a subset from the ATP cohort for analysis of immunogenicity, in subjects for which a blood sample was taken at Month 2 and were seronegative for anti-HAV before vaccination, i.e. with anti-HAV antibody titers below 15 mIU/mL.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cervarix™ & Twinrix™ Group | Anti-HAV Antibody Titers | 467.0 mIU/mL |
| Twinrix™ Group | Anti-HAV Antibody Titers | 513.9 mIU/mL |
Secondary
Anti-HBs Antibody Titers
Titers are given as Geometric Mean Titers (GMTs)expressed as mIU/mL.
Time frame: At Month 7
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity, in subjects seronegative for anti-HBs before vaccination, i.e. with anti-HBs antibody titers below 3.3 mIU/mL.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cervarix™ & Twinrix™ Group | Anti-HBs Antibody Titers | 3136.5 mIU/mL |
| Twinrix™ Group | Anti-HBs Antibody Titers | 5646.5 mIU/mL |
Secondary
Anti-HBs Antibody Titers
Titers are given as geometric mean titers (GMTs) expressed as mIU/mL.
Time frame: One month after the second dose of vaccine
Population: Analysis was performed on a subset from the ATP cohort for analysis of immunogenicity, in subjects for which a blood sample was taken at Month 2 and were seronegative for anti-HBs before vaccination, i.e. with antibody titers below 3.3 mIU/mL.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cervarix™ & Twinrix™ Group | Anti-HBs Antibody Titers | 33.7 mIU/mL |
| Twinrix™ Group | Anti-HBs Antibody Titers | 43.0 mIU/mL |
Secondary
Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers
Titers are given as Geometric Mean Titers (GMTs) expressed as EL.U/mL.
Time frame: One month after the second dose of vaccine
Population: Analysis was performed on a subset from the ATP cohort for analysis of immunogenicity, in subjects for which a blood sample was taken at Month 2 and were seronegative for the corresponding HPV type before vaccination, i.e. with antibody titers below 8 EL.U/mL for anti-HPV-16 antibodies and below 7 EL.U/mL for anti-HPV-18 antibodies.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix™ & Twinrix™ Group | Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers | Anti-HPV-16 GMTs | 5215.2 EL.U/mL |
| Cervarix™ & Twinrix™ Group | Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers | Anti-HPV-18 GMTs | 4496.8 EL.U/mL |
| Cervarix™ Group | Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers | Anti-HPV-16 GMTs | 4967.2 EL.U/mL |
| Cervarix™ Group | Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers | Anti-HPV-18 GMTs | 4266.5 EL.U/mL |
Secondary
Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers in Vaccine Recipients Aged 9 Years
Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).
Time frame: At Month 7
Population: Analysis was performed in 9-year old subjects from the ATP cohort for analysis of immunogenicity, who were seronegative for the corresponding HPV type before vaccination, i.e. with antibody titers below 8 EL.U/mL for anti-HPV-16 antibodies and below 7 EL.U/mL for anti-HPV-18 antibodies.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 9-Year Old Cervarix Vaccine Recipients | Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers in Vaccine Recipients Aged 9 Years | Anti-HPV-16 GMTs | 32170.2 EL.U/mL |
| 9-Year Old Cervarix Vaccine Recipients | Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers in Vaccine Recipients Aged 9 Years | Anti-HPV-18 GMTs | 12257.1 EL.U/mL |
Secondary
Number of Subjects Reporting Medically Significant Conditions
Medically significant conditions include adverse events (AEs) prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
Time frame: Throughout the active phase of the study (up to Month 7)
Population: Analysis was performed on the Total Vaccinated Cohort, on subjects with available data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Medically Significant Conditions | 22 Participants |
| Cervarix™ Group | Number of Subjects Reporting Medically Significant Conditions | 23 Participants |
| Twinrix™ Group | Number of Subjects Reporting Medically Significant Conditions | 31 Participants |
Secondary
Number of Subjects Reporting Medically Significant Conditions
Medically significant conditions include adverse events (AEs) prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
Time frame: Throughout the safety follow-up (from Month 7 up to Month 12)
Population: Analysis was performed on the Total Vaccinated Cohort, on subjects with available data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Medically Significant Conditions | 2 Participants |
| Cervarix™ Group | Number of Subjects Reporting Medically Significant Conditions | 2 Participants |
| Twinrix™ Group | Number of Subjects Reporting Medically Significant Conditions | 1 Participants |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAE)
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: Throughout the study (up to Month 12)
Population: Analysis was performed on the Total Vaccinated Cohort, on subjects with available data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Serious Adverse Events (SAE) | 2 Participants |
| Cervarix™ Group | Number of Subjects Reporting Serious Adverse Events (SAE) | 4 Participants |
| Twinrix™ Group | Number of Subjects Reporting Serious Adverse Events (SAE) | 4 Participants |
Secondary
Number of Subjects Reporting Solicited General Symptoms
Solicited general symptoms assessed include arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, temperature \[axillary route, greater than or equal to 37.5 degree Celsius (°C)\] and urticaria.
Time frame: During the 7-day period following vaccination
Population: Analysis was performed on the Total Vaccinated Cohort, on subjects with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Headache | 125 Participants |
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Fatigue | 122 Participants |
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Gastrointestinal | 70 Participants |
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Fever | 24 Participants |
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Urticaria | 6 Participants |
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Rash | 18 Participants |
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Arthralgia | 50 Participants |
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Myalgia | 103 Participants |
| Cervarix™ Group | Number of Subjects Reporting Solicited General Symptoms | Fever | 28 Participants |
| Cervarix™ Group | Number of Subjects Reporting Solicited General Symptoms | Rash | 21 Participants |
| Cervarix™ Group | Number of Subjects Reporting Solicited General Symptoms | Urticaria | 11 Participants |
| Cervarix™ Group | Number of Subjects Reporting Solicited General Symptoms | Myalgia | 99 Participants |
| Cervarix™ Group | Number of Subjects Reporting Solicited General Symptoms | Gastrointestinal | 65 Participants |
| Cervarix™ Group | Number of Subjects Reporting Solicited General Symptoms | Fatigue | 133 Participants |
| Cervarix™ Group | Number of Subjects Reporting Solicited General Symptoms | Headache | 124 Participants |
| Cervarix™ Group | Number of Subjects Reporting Solicited General Symptoms | Arthralgia | 45 Participants |
| Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Urticaria | 9 Participants |
| Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Arthralgia | 40 Participants |
| Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Fatigue | 119 Participants |
| Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Fever | 14 Participants |
| Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Gastrointestinal | 72 Participants |
| Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Headache | 110 Participants |
| Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Myalgia | 75 Participants |
| Twinrix™ Group | Number of Subjects Reporting Solicited General Symptoms | Rash | 12 Participants |
Secondary
Number of Subjects Reporting Solicited Local Symptoms
Solicited local symptoms assessed include injection site pain, redness and swelling. Data are presented across doses.
Time frame: During the 7-day period (Day 0-6) following vaccination
Population: Analysis was performed on the Total Vaccinated Cohort, on subjects with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Solicited Local Symptoms | Swelling | 146 Participants |
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Solicited Local Symptoms | Redness | 155 Participants |
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Solicited Local Symptoms | Pain | 251 Participants |
| Cervarix™ Group | Number of Subjects Reporting Solicited Local Symptoms | Swelling | 137 Participants |
| Cervarix™ Group | Number of Subjects Reporting Solicited Local Symptoms | Pain | 250 Participants |
| Cervarix™ Group | Number of Subjects Reporting Solicited Local Symptoms | Redness | 170 Participants |
| Twinrix™ Group | Number of Subjects Reporting Solicited Local Symptoms | Redness | 74 Participants |
| Twinrix™ Group | Number of Subjects Reporting Solicited Local Symptoms | Pain | 202 Participants |
| Twinrix™ Group | Number of Subjects Reporting Solicited Local Symptoms | Swelling | 56 Participants |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events
Unsolicited adverse events include any adverse event reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.
Time frame: During the 30-day period following any vaccination
Population: Analysis was performed on the Total Vaccinated Cohort, on subjects with available data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix™ & Twinrix™ Group | Number of Subjects Reporting Unsolicited Adverse Events | 83 Participants |
| Cervarix™ Group | Number of Subjects Reporting Unsolicited Adverse Events | 96 Participants |
| Twinrix™ Group | Number of Subjects Reporting Unsolicited Adverse Events | 83 Participants |
Secondary
Number of Subjects Seroconverted and Number of Subjects Seroprotected for Anti-HBs Antibodies
Seroconversion is defined as the appearance of anti-HBs antibodies (i.e., antibody titer greater than or equal to 3.3 mIU/mL) in the sera of subjects seronegative (with antibody titers below 3.3 mIU/mL) before vaccination. A seroprotected subject against HBs is a subject with antibody titers greater than or equal to 10 mIU/mL.
Time frame: One month after the second dose of vaccine
Population: Analysis was performed on a subset from the ATP cohort for analysis of immunogenicity, in subjects for which a blood sample was taken at Month 2 and were seronegative for anti-HBs with antibody titers below 3.3 mIU/mL.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix™ & Twinrix™ Group | Number of Subjects Seroconverted and Number of Subjects Seroprotected for Anti-HBs Antibodies | Seroconverted | 68 Participants |
| Cervarix™ & Twinrix™ Group | Number of Subjects Seroconverted and Number of Subjects Seroprotected for Anti-HBs Antibodies | Seroprotected | 60 Participants |
| Twinrix™ Group | Number of Subjects Seroconverted and Number of Subjects Seroprotected for Anti-HBs Antibodies | Seroconverted | 56 Participants |
| Twinrix™ Group | Number of Subjects Seroconverted and Number of Subjects Seroprotected for Anti-HBs Antibodies | Seroprotected | 53 Participants |
Secondary
Number of Subjects Seroconverted for Anti-HAV Antibodies
Seroconversion is defined as the appearance of anti-HAV antibodies (i.e., antibody titer greater than or equal to 15 mIU/mL) in the sera of subjects seronegative (antibody titer below 15 mIU/mL) before vaccination.
Time frame: One month after the second dose of vaccine
Population: Analysis was performed on a subset from the ATP cohort for analysis of immunogenicity, in subjects for which a blood sample was taken at Month 2 and were seronegative for anti-HAV before vaccination, i.e. with anti-HAV antibody titers below 15 mIU/mL.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix™ & Twinrix™ Group | Number of Subjects Seroconverted for Anti-HAV Antibodies | 112 Participants |
| Twinrix™ Group | Number of Subjects Seroconverted for Anti-HAV Antibodies | 112 Participants |
Secondary
Number of Subjects Seroconverted for Anti-HBs Antibodies
Seroconversion is defined as the appearance of anti-HBs antibodies (i.e., antibody titer greater than or equal to 3.3 mIU/mL) in the sera of subjects seronegative (with antibody titers below 3.3 mIU/mL) before vaccination.
Time frame: At month 7
Population: Analysis was performed on the ATP cohort for analysis of immunogenicity, in subjects seronegative for anti-HBs before vaccination.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix™ & Twinrix™ Group | Number of Subjects Seroconverted for Anti-HBs Antibodies | 175 Participants |
| Twinrix™ Group | Number of Subjects Seroconverted for Anti-HBs Antibodies | 161 Participants |
Secondary
Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies
Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values assessed include 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.
Time frame: One month after the second dose of vaccine
Population: Analysis was performed on a subset from the ATP cohort for analysis of immunogenicity, in subjects for which a blood sample was taken at Month 2 and were seronegative for the corresponding HPV type before vaccination, i.e. with antibody titers below 8 EL.U/mL for anti-HPV-16 antibodies and below 7 EL.U/mL for anti-HPV-18 antibodies.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix™ & Twinrix™ Group | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-16 | 105 Participants |
| Cervarix™ & Twinrix™ Group | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-18 | 112 Participants |
| Cervarix™ Group | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-16 | 106 Participants |
| Cervarix™ Group | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-18 | 111 Participants |
Secondary
Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies in Vaccine Recipients Aged 9 Years
Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values = 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.
Time frame: At Month 7
Population: Analysis was performed in 9-year old subjects from the ATP cohort for analysis of immunogenicity, who were seronegative for the corresponding HPV type before vaccination, i.e. with antibody titers below 8 EL.U/mL for anti-HPV-16 antibodies and below 7 EL.U/mL for anti-HPV-18 antibodies.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 9-Year Old Cervarix Vaccine Recipients | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies in Vaccine Recipients Aged 9 Years | Anti-HPV-16 | 156 Participants |
| 9-Year Old Cervarix Vaccine Recipients | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies in Vaccine Recipients Aged 9 Years | Anti-HPV-18 | 161 Participants |