Infections, Papillomavirus
Conditions
Keywords
Human Papillomavirus
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/adolescents platform. Therefore, this Phase IIIb study is designed to evaluate the safety and immunogenicity of co-administering Boostrix polio (dTpa-IPV) with GSK Biologicals' (580299)HPV-16/18 L1 AS04 vaccine (Cervarix TM) as compared to the administration of either vaccine alone. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Interventions
BIOLOGICALBoostrix ® Polio
One dose of vaccine administered intramuscularly
BIOLOGICALGSK Biologicals' HPV-16/18 L1 AS04 vaccine (Cervarix TM)
Three doses of vaccine administered intramuscularly, with the second and third dose give one month and six months after the first dose respectively
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
10 Years to 18 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that they and their parents/legally acceptable representatives can, and will, comply with the requirements of the protocol should be enrolled in the study. * A female between, and including, 10 and 18 years of age at the time of the first vaccination. * Written informed consent/assent obtained from the subject prior to enrolment. For subjects above the legal age of consent, written informed consent must be obtained from the subject. For subjects below legal age of consent, written informed consent obtained from the subject's parent/LAR, and written informed assent must be obtained from the subject. * Healthy subjects, as established by medical history and history-directed physical examination, before entering into the study. * Previously completed routine childhood vaccinations according to the recommended vaccination schedule at the time. * Subjects must have a negative urine pregnancy test. * Subject must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series. Subjects who reach menarche during the study, and therefore become of childbearing potential, must agree to follow the same precautions.
Exclusion criteria
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 12/13). * Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). * 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 up to 8 days before the first dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window. * A woman 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 * Administration of a diphtheria, tetanus, pertussis (DTP) vaccine, diphtheria-tetanus (Td) booster or dTpa vaccine within the previous five years. * Administration of a pre-school booster of Oral Polio Vaccine (OPV) or Inactivated Polio Virus (IPV) vaccine (4 or 5th dose) within the previous five years. * Hypersensitivity to latex. * Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality or thrombocytopenia, 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. * History of encephalopathy within seven days of administration of a previous dose of pertussis vaccine that is not attributable to another identifiable cause. * Temperature of \>=40°C within 48 hours of receipt of a prior dose of DTP vaccine (DTPw and/or DTPa), not due to another identifiable cause. * Collapse or shock-like state within 48 hours of receipt of a prior dose of DTP vaccine (DTPw and/or DTPa). * Seizures with or without fever within three days of a prior dose of DTP vaccine (Diphtheria, Tetanus, whole cell Pertussis vaccine DTPw and/or Diphtheria, Tetanus, acellular Pertussis vaccine DTPa). * Persistent, inconsolable crying lasting \>=3 hours, occurring within 48 hours of a prior dose of DTP vaccine (DTPw and/or DTPa). * Severe Arthus-type hypersensitivity reactions following a prior dose of tetanus toxoid within the previous 10 years. * Known exposure to diphtheria or household exposure to pertussis within 30 days before (i.e., Day 0-29) vaccination with Diphtheria, Tetanus, acellular Pertussis and inactivated polio virus vaccine (dTpa-IPV). * Diphtheria and/or tetanus and/or pertussis and/or polio diagnosed within 30 days before (i.e., Day 0-29) vaccination with dTpa-IPV. * Presence of a contra-indication to vaccination according to the product leaflet of the commercially available dTpa-IPV vaccine. * 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 3 months preceding the first dose of study vaccine or planned administration during the study period. Enrolment will be postponed until the subject is outside the specified window.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Seroprotected Against Diphtheria and Tetanus | One month after vaccination with Boostrix Polio | Seroprotection against diphtheria and tetanus is defined as anti-diphtheria and anti-tetanus antibody titres greater than or equal to 0.1 International Units per Milliliter (≥ 0.1 IU/mL). |
| Titers of Anti-pertussis Toxoid (Anti-PT), Anti-pertactin Toxoid (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) Antibodies | One month after vaccination with Boostrix Polio | Titers are given as geometric mean titers (GMTs) calculated on all subjects and expressed as Enzyme-linked Immunosorbent Assay Units per Milliliter (EL.U/mL). |
| Number of Subjects Seroprotected Against Poliovirus Type 1 (Polio 1), Polio 2 and Polio 3 | One month after vaccination with Boostrix Polio | Seroprotection against polio 1, 2 and 3 is defined as anti-polio 1, 2 and 3 antibody titers greater than or equal to 8 Effective Dose 50% (≥ 8 ED50). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Titers of Anti-diphtheria and Anti-tetanus Antibodies | One month after vaccination with Boostrix-Polio | Titers are given as Geometric Mean Titers (GMTs) and expressed as IU/mL. |
| Number of Subjects With Anti-diphtheria and Anti-tetanus Antibody Titers Above 1.0 International Units Per Milliliter (IU/mL) | One month after vaccination with Boostrix Polio | Anti-diphtheria and anti-tetanus antibodies cut-off value assessed include 1.0 IU/mL. |
| Anti-poliovirus Type 1 (Anti-polio 1), Anti-polio 2 and Anti-polio 3 Antibody Titers | One month after vaccination with Boostrix Polio | Titers are given as Geometric Mean Titers (GMTs). The titer is a serum dilution giving 50 percent reduction of signal compared to control without serum. |
| Number of Subjects With Booster Response to Diphtheria and Tetanus | One month after vaccination with Boostrix Polio | Booster responses to diphtheria and tetanus were defined as: * For initially seronegative subjects (pre-vaccination titer below cut-off value of 0.1 International Units per Milliliter): antibody titers at least four times the cut-off (post-vaccination titer greater than or equal to 0.4 IU/mL), and * For initially seropositive subjects (pre-vaccination titer greater than or equal to 0.1 IU/mL): an increase in antibody titers of at least four times the pre-vaccination titer. |
| Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-HPV-18 Antibodies After Completing the Cervarix Vaccination Course | One month post Cervarix Dose 3 (Month 7/8) | 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. |
| Number of Subjects Reporting Solicited Symptoms | During the 7-day period (Day 0-6) following each vaccination | Solicited local symptoms assessed include pain, redness and swelling at the injection site. Solicited general symptoms assessed include arthralgia, fatigue, fever (above 37.5 degree Celsius), gastrointestinal symptoms, headache, myalgia, rash and urticaria. |
| Number of Subjects Reporting Unsolicited Adverse Events | During the 30-day period (Day 0-29) following vaccination | Unsolicited adverse event = Any adverse event (AE) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. |
| Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (MSAEs) | During the active phase of the study (up to Month 7/8) and during the safety follow-up (up to Month 12/13) | NOCDs assessed include e.g. autoimmune disorders, asthma, type I diabetes. MSAEs assessed include AEs prompting emergency room or physician visits that are not related to common diseases or SAEs that are not related to common diseases. |
| Number of Subjects Reporting Serious Adverse Events (SAEs) | During the active phase of the study (up to Month 7/8) and during the safety follow-up (up to Month 12/13) | Serious adverse events assessed include medical occurrences that results 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 With Booster Response to Pertussis Toxoid (PT), Pertactin Toxoid (PRN) and Filamentous Hemagglutinin (FHA) | One month after vaccination with Boostrix Polio | Booster response to PT, FHA and PRN were defined as: * For initially seronegative subjects \[pre-vaccination titer below cut-off value of 5 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL)\]: antibody titers at least 4 times the cut-off, * For initially seropositive subjects with pre-vaccination titer above 5 EL.U/mL and \< 20 EL.U/mL: an increase in antibody titers of at least 4 times the pre-vaccination titer, * For initially seropositive subjects with pre-vaccination titer above 20 EL.U/mL: an increase in antibody titers of at least 2 times the pre-vaccination titer. |
| Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies After Incomplete Cervarix Vaccination Course | One month post Dose 1 | 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. |
| Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies After Completing the Cervarix Vaccination Course | One month post Cervarix Dose 3 (Month 7/8)] | Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL). |
Countries
France, Germany, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cervarix Group Subjects who received GSK Biologicals HPV 16/18 vaccine 580299 (CervarixTM) at Month 0, 1 and 6. | 248 |
| Cervarix + Boostrix Polio Group Subjects who received GSK Biologicals HPV 16/18 vaccine 580299 (CervarixTM) at Month 0, 1 and 6 with co-administration of Boostrix™ Polio at Month 0. | 255 |
| Boostrix Polio → Cervarix Group Subjects who received Boostrix™ Polio at Month 0 and GSK Biologicals HPV 16/18 vaccine 580299 (CervarixTM) at Month 1, 2 and 7. | 248 |
| Total | 751 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 2 | 5 |
| Overall Study | Withdrawal by Subject | 1 | 3 | 0 |
Baseline characteristics
| Characteristic | Cervarix Group | Cervarix + Boostrix Polio Group | Boostrix Polio → Cervarix Group | Total |
|---|---|---|---|---|
| Age, Continuous Active phase (up to Month 7/8) | 13.9 years STANDARD_DEVIATION 2.59 | 14.0 years STANDARD_DEVIATION 2.43 | 13.9 years STANDARD_DEVIATION 2.47 | 13.9 years STANDARD_DEVIATION 2.5 |
| Age, Continuous Safety follow-up (up to Month 12/13) | 13.9 years STANDARD_DEVIATION 2.58 | 13.9 years STANDARD_DEVIATION 2.41 | 13.8 years STANDARD_DEVIATION 2.46 | 13.9 years STANDARD_DEVIATION 2.48 |
| Sex: Female, Male Female | 248 Participants | 255 Participants | 248 Participants | 751 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 | 232 / 248 | 245 / 255 | 242 / 248 |
| serious Total, serious adverse events | 3 / 248 | 4 / 255 | 3 / 248 |
Outcome results
Primary
Number of Subjects Seroprotected Against Diphtheria and Tetanus
Seroprotection against diphtheria and tetanus is defined as anti-diphtheria and anti-tetanus antibody titres greater than or equal to 0.1 International Units per Milliliter (≥ 0.1 IU/mL).
Time frame: One month after vaccination with Boostrix Polio
Population: Analysis was performed on the Month 1 According-to-Protocol (ATP) cohort for analysis of immunogenicity and only on those subjects vaccinated with Boostrix Polio.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix + Boostrix Polio Group | Number of Subjects Seroprotected Against Diphtheria and Tetanus | Diphtheria | 238 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Seroprotected Against Diphtheria and Tetanus | Tetanus | 240 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Seroprotected Against Diphtheria and Tetanus | Diphtheria | 233 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Seroprotected Against Diphtheria and Tetanus | Tetanus | 233 Participants |
Primary
Number of Subjects Seroprotected Against Poliovirus Type 1 (Polio 1), Polio 2 and Polio 3
Seroprotection against polio 1, 2 and 3 is defined as anti-polio 1, 2 and 3 antibody titers greater than or equal to 8 Effective Dose 50% (≥ 8 ED50).
Time frame: One month after vaccination with Boostrix Polio
Population: Analysis was performed on the Month 1 According-to-Protocol (ATP) cohort for analysis of immunogenicity and only on those subjects vaccinated with Boostrix Polio and with available results for the defined antigen.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix + Boostrix Polio Group | Number of Subjects Seroprotected Against Poliovirus Type 1 (Polio 1), Polio 2 and Polio 3 | Polio 2 | 240 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Seroprotected Against Poliovirus Type 1 (Polio 1), Polio 2 and Polio 3 | Polio 1 | 239 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Seroprotected Against Poliovirus Type 1 (Polio 1), Polio 2 and Polio 3 | Polio 3 | 239 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Seroprotected Against Poliovirus Type 1 (Polio 1), Polio 2 and Polio 3 | Polio 1 | 231 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Seroprotected Against Poliovirus Type 1 (Polio 1), Polio 2 and Polio 3 | Polio 2 | 232 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Seroprotected Against Poliovirus Type 1 (Polio 1), Polio 2 and Polio 3 | Polio 3 | 232 Participants |
Primary
Titers of Anti-pertussis Toxoid (Anti-PT), Anti-pertactin Toxoid (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) Antibodies
Titers are given as geometric mean titers (GMTs) calculated on all subjects and expressed as Enzyme-linked Immunosorbent Assay Units per Milliliter (EL.U/mL).
Time frame: One month after vaccination with Boostrix Polio
Population: Analysis was performed on the Month 1 According-to-Protocol (ATP) cohort for analysis of immunogenicity and only on those subjects vaccinated with Boostrix Polio.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix + Boostrix Polio Group | Titers of Anti-pertussis Toxoid (Anti-PT), Anti-pertactin Toxoid (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) Antibodies | Anti-PT | 84.2 EL.U/mL |
| Cervarix + Boostrix Polio Group | Titers of Anti-pertussis Toxoid (Anti-PT), Anti-pertactin Toxoid (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) Antibodies | Anti-FHA | 611.7 EL.U/mL |
| Cervarix + Boostrix Polio Group | Titers of Anti-pertussis Toxoid (Anti-PT), Anti-pertactin Toxoid (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) Antibodies | Anti-PRN | 426.2 EL.U/mL |
| Boostrix Polio → Cervarix Group | Titers of Anti-pertussis Toxoid (Anti-PT), Anti-pertactin Toxoid (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) Antibodies | Anti-PT | 75.4 EL.U/mL |
| Boostrix Polio → Cervarix Group | Titers of Anti-pertussis Toxoid (Anti-PT), Anti-pertactin Toxoid (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) Antibodies | Anti-FHA | 615.2 EL.U/mL |
| Boostrix Polio → Cervarix Group | Titers of Anti-pertussis Toxoid (Anti-PT), Anti-pertactin Toxoid (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) Antibodies | Anti-PRN | 360.0 EL.U/mL |
Secondary
Anti-poliovirus Type 1 (Anti-polio 1), Anti-polio 2 and Anti-polio 3 Antibody Titers
Titers are given as Geometric Mean Titers (GMTs). The titer is a serum dilution giving 50 percent reduction of signal compared to control without serum.
Time frame: One month after vaccination with Boostrix Polio
Population: Analysis was performed on the Month 1 According-to-Protocol (ATP) cohort for analysis of immunogenicity and only on those subjects vaccinated with Boostrix Polio.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix + Boostrix Polio Group | Anti-poliovirus Type 1 (Anti-polio 1), Anti-polio 2 and Anti-polio 3 Antibody Titers | Anti-polio 1 | 2045.1 titer |
| Cervarix + Boostrix Polio Group | Anti-poliovirus Type 1 (Anti-polio 1), Anti-polio 2 and Anti-polio 3 Antibody Titers | Anti-polio 2 | 2151.1 titer |
| Cervarix + Boostrix Polio Group | Anti-poliovirus Type 1 (Anti-polio 1), Anti-polio 2 and Anti-polio 3 Antibody Titers | Anti-polio 3 | 2777.2 titer |
| Boostrix Polio → Cervarix Group | Anti-poliovirus Type 1 (Anti-polio 1), Anti-polio 2 and Anti-polio 3 Antibody Titers | Anti-polio 3 | 2732.5 titer |
| Boostrix Polio → Cervarix Group | Anti-poliovirus Type 1 (Anti-polio 1), Anti-polio 2 and Anti-polio 3 Antibody Titers | Anti-polio 1 | 2390.5 titer |
| Boostrix Polio → Cervarix Group | Anti-poliovirus Type 1 (Anti-polio 1), Anti-polio 2 and Anti-polio 3 Antibody Titers | Anti-polio 2 | 2158.1 titer |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs)
Serious adverse events assessed include medical occurrences that results 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: During the active phase of the study (up to Month 7/8) and during the safety follow-up (up to Month 12/13)
Population: Analysis was performed on the Total Vaccinated Cohort (for the active phase) and on the Extended Safety Follow-up Vaccinated Cohort (for the safety follow-up).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | Active phase | 2 Participants |
| Cervarix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | Safety follow-up | 1 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | Active phase | 4 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | Safety follow-up | 0 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | Active phase | 2 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | Safety follow-up | 1 Participants |
Secondary
Number of Subjects Reporting Solicited Symptoms
Solicited local symptoms assessed include pain, redness and swelling at the injection site. Solicited general symptoms assessed include arthralgia, fatigue, fever (above 37.5 degree Celsius), gastrointestinal symptoms, headache, myalgia, rash and urticaria.
Time frame: During the 7-day period (Day 0-6) following each vaccination
Population: Analysis was performed on the Total Vaccinated Cohort, on subjects with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Myalgia | 107 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Fatigue | 109 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Arthralgia | 58 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Swelling | 124 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Fever | 30 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Urticaria | 12 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Redness | 110 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Gastrointestinal symptoms | 51 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Pain | 225 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Rash | 20 Participants |
| Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Headache | 111 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Solicited Symptoms | Pain | 237 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Solicited Symptoms | Swelling | 125 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Solicited Symptoms | Myalgia | 144 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Solicited Symptoms | Rash | 27 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Solicited Symptoms | Urticaria | 11 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Solicited Symptoms | Arthralgia | 71 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Solicited Symptoms | Headache | 138 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Solicited Symptoms | Fatigue | 135 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Solicited Symptoms | Fever | 46 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Solicited Symptoms | Gastrointestinal symptoms | 63 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Solicited Symptoms | Redness | 128 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Urticaria | 15 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Pain | 233 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Swelling | 123 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Arthralgia | 77 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Fatigue | 121 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Fever | 37 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Gastrointestinal symptoms | 61 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Headache | 122 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Myalgia | 127 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Rash | 17 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Solicited Symptoms | Redness | 140 Participants |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events
Unsolicited adverse event = Any adverse event (AE) reported in addition to those solicited during the clinical study. Also any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.
Time frame: During the 30-day period (Day 0-29) following vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix Group | Number of Subjects Reporting Unsolicited Adverse Events | 85 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Unsolicited Adverse Events | 74 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Unsolicited Adverse Events | 99 Participants |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (MSAEs)
NOCDs assessed include e.g. autoimmune disorders, asthma, type I diabetes. MSAEs assessed include AEs prompting emergency room or physician visits that are not related to common diseases or SAEs that are not related to common diseases.
Time frame: During the active phase of the study (up to Month 7/8) and during the safety follow-up (up to Month 12/13)
Population: Analysis was performed on the Total Vaccinated Cohort (for the active phase) and on the Extended Safety Follow-up Vaccinated Cohort (for the safety follow-up).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (MSAEs) | NOCDs [Active phase] | 5 Participants |
| Cervarix Group | Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (MSAEs) | NOCDs [Safety follow-up] | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (MSAEs) | MSAEs [Active phase] | 35 Participants |
| Cervarix Group | Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (MSAEs) | MSAEs [Safety follow-up] | 7 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (MSAEs) | MSAEs [Safety follow-up] | 3 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (MSAEs) | NOCDs [Active phase] | 9 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (MSAEs) | MSAEs [Active phase] | 27 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (MSAEs) | NOCDs [Safety follow-up] | 0 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (MSAEs) | MSAEs [Safety follow-up] | 5 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (MSAEs) | NOCDs [Safety follow-up] | 0 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (MSAEs) | MSAEs [Active phase] | 49 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (MSAEs) | NOCDs [Active phase] | 9 Participants |
Secondary
Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies After Incomplete Cervarix Vaccination Course
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 post Dose 1
Population: Analysis was performed on the Month 1 According-to-Protocol (ATP) cohort for analysis of immunogenicity and only on subjects from the Cervarix and Cervarix + Boostrix Polio groups with available results for the defined antibody.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies After Incomplete Cervarix Vaccination Course | Anti-HPV-16 | 198 Participants |
| Cervarix Group | Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies After Incomplete Cervarix Vaccination Course | Anti-HPV-18 | 191 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies After Incomplete Cervarix Vaccination Course | Anti-HPV-16 | 201 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies After Incomplete Cervarix Vaccination Course | Anti-HPV-18 | 203 Participants |
Secondary
Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-HPV-18 Antibodies After Completing the Cervarix Vaccination Course
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 post Cervarix Dose 3 (Month 7/8)
Population: Analysis was performed on the Month 7/8 According-to-Protocol (ATP) cohort for analysis of immunogenicity on subjects with available results for the defined antibody.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-HPV-18 Antibodies After Completing the Cervarix Vaccination Course | Anti-HPV-16 | 198 Participants |
| Cervarix Group | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-HPV-18 Antibodies After Completing the Cervarix Vaccination Course | Anti-HPV-18 | 191 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-HPV-18 Antibodies After Completing the Cervarix Vaccination Course | Anti-HPV-16 | 201 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-HPV-18 Antibodies After Completing the Cervarix Vaccination Course | Anti-HPV-18 | 203 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-HPV-18 Antibodies After Completing the Cervarix Vaccination Course | Anti-HPV-16 | 204 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-HPV-18 Antibodies After Completing the Cervarix Vaccination Course | Anti-HPV-18 | 203 Participants |
Secondary
Number of Subjects With Anti-diphtheria and Anti-tetanus Antibody Titers Above 1.0 International Units Per Milliliter (IU/mL)
Anti-diphtheria and anti-tetanus antibodies cut-off value assessed include 1.0 IU/mL.
Time frame: One month after vaccination with Boostrix Polio
Population: Analysis was performed on the Month 1 According-to-Protocol (ATP) cohort for analysis of immunogenicity and only on those subjects vaccinated with Boostrix Polio.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix + Boostrix Polio Group | Number of Subjects With Anti-diphtheria and Anti-tetanus Antibody Titers Above 1.0 International Units Per Milliliter (IU/mL) | Anti-diphtheria | 231 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects With Anti-diphtheria and Anti-tetanus Antibody Titers Above 1.0 International Units Per Milliliter (IU/mL) | Anti-tetanus | 239 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects With Anti-diphtheria and Anti-tetanus Antibody Titers Above 1.0 International Units Per Milliliter (IU/mL) | Anti-diphtheria | 226 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects With Anti-diphtheria and Anti-tetanus Antibody Titers Above 1.0 International Units Per Milliliter (IU/mL) | Anti-tetanus | 233 Participants |
Secondary
Number of Subjects With Booster Response to Diphtheria and Tetanus
Booster responses to diphtheria and tetanus were defined as: * For initially seronegative subjects (pre-vaccination titer below cut-off value of 0.1 International Units per Milliliter): antibody titers at least four times the cut-off (post-vaccination titer greater than or equal to 0.4 IU/mL), and * For initially seropositive subjects (pre-vaccination titer greater than or equal to 0.1 IU/mL): an increase in antibody titers of at least four times the pre-vaccination titer.
Time frame: One month after vaccination with Boostrix Polio
Population: Analysis was performed on the Month 1 According-to-Protocol (ATP) cohort for analysis of immunogenicity and only on those subjects vaccinated with Boostrix Polio.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix + Boostrix Polio Group | Number of Subjects With Booster Response to Diphtheria and Tetanus | Diphtheria | 160 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects With Booster Response to Diphtheria and Tetanus | Tetanus | 167 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects With Booster Response to Diphtheria and Tetanus | Diphtheria | 159 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects With Booster Response to Diphtheria and Tetanus | Tetanus | 161 Participants |
Secondary
Number of Subjects With Booster Response to Pertussis Toxoid (PT), Pertactin Toxoid (PRN) and Filamentous Hemagglutinin (FHA)
Booster response to PT, FHA and PRN were defined as: * For initially seronegative subjects \[pre-vaccination titer below cut-off value of 5 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL)\]: antibody titers at least 4 times the cut-off, * For initially seropositive subjects with pre-vaccination titer above 5 EL.U/mL and \< 20 EL.U/mL: an increase in antibody titers of at least 4 times the pre-vaccination titer, * For initially seropositive subjects with pre-vaccination titer above 20 EL.U/mL: an increase in antibody titers of at least 2 times the pre-vaccination titer.
Time frame: One month after vaccination with Boostrix Polio
Population: Analysis was performed on the Month 1 According-to-Protocol (ATP) cohort for analysis of immunogenicity and only on those subjects vaccinated with Boostrix Polio.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix + Boostrix Polio Group | Number of Subjects With Booster Response to Pertussis Toxoid (PT), Pertactin Toxoid (PRN) and Filamentous Hemagglutinin (FHA) | FHA | 210 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects With Booster Response to Pertussis Toxoid (PT), Pertactin Toxoid (PRN) and Filamentous Hemagglutinin (FHA) | PRN | 222 Participants |
| Cervarix + Boostrix Polio Group | Number of Subjects With Booster Response to Pertussis Toxoid (PT), Pertactin Toxoid (PRN) and Filamentous Hemagglutinin (FHA) | PT | 199 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects With Booster Response to Pertussis Toxoid (PT), Pertactin Toxoid (PRN) and Filamentous Hemagglutinin (FHA) | PRN | 207 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects With Booster Response to Pertussis Toxoid (PT), Pertactin Toxoid (PRN) and Filamentous Hemagglutinin (FHA) | PT | 182 Participants |
| Boostrix Polio → Cervarix Group | Number of Subjects With Booster Response to Pertussis Toxoid (PT), Pertactin Toxoid (PRN) and Filamentous Hemagglutinin (FHA) | FHA | 205 Participants |
Secondary
Titers of Anti-diphtheria and Anti-tetanus Antibodies
Titers are given as Geometric Mean Titers (GMTs) and expressed as IU/mL.
Time frame: One month after vaccination with Boostrix-Polio
Population: Analysis was performed on the Month 1 According-to-Protocol (ATP) cohort for analysis of immunogenicity and only on those subjects vaccinated with Boostrix Polio.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix + Boostrix Polio Group | Titers of Anti-diphtheria and Anti-tetanus Antibodies | Anti-diphtheria | 5.085 IU/mL |
| Cervarix + Boostrix Polio Group | Titers of Anti-diphtheria and Anti-tetanus Antibodies | Anti-tetanus | 8.552 IU/mL |
| Boostrix Polio → Cervarix Group | Titers of Anti-diphtheria and Anti-tetanus Antibodies | Anti-diphtheria | 5.466 IU/mL |
| Boostrix Polio → Cervarix Group | Titers of Anti-diphtheria and Anti-tetanus Antibodies | Anti-tetanus | 9.039 IU/mL |
Secondary
Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies After Completing the Cervarix Vaccination Course
Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).
Time frame: One month post Cervarix Dose 3 (Month 7/8)]
Population: Analysis was performed on the Month 7/8 According-to-Protocol (ATP) cohort for analysis of immunogenicity on subjects with available results for the defined antibody.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies After Completing the Cervarix Vaccination Course | Anti-HPV-16 | 18363.6 EL.U/mL |
| Cervarix Group | Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies After Completing the Cervarix Vaccination Course | Anti-HPV-18 | 7032.8 EL.U/mL |
| Cervarix + Boostrix Polio Group | Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies After Completing the Cervarix Vaccination Course | Anti-HPV-16 | 15370.2 EL.U/mL |
| Cervarix + Boostrix Polio Group | Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies After Completing the Cervarix Vaccination Course | Anti-HPV-18 | 6630.4 EL.U/mL |
| Boostrix Polio → Cervarix Group | Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies After Completing the Cervarix Vaccination Course | Anti-HPV-16 | 14089.5 EL.U/mL |
| Boostrix Polio → Cervarix Group | Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies After Completing the Cervarix Vaccination Course | Anti-HPV-18 | 5135.0 EL.U/mL |