Infections, Papillomavirus
Conditions
Keywords
Safety, HPV vaccine, Immune response, Human papillomavirus, China
Brief summary
This study is designed to evaluate the immunogenicity and safety of GSK Biologicals' human papillomavirus (HPV) vaccine in adult female subjects aged 26-45 years. One group of subjects will receive the HPV vaccine and the other group will receive an active control (GSK Biologicals' hepatitis B vaccine). Immunogenicity data of the HPV group will be compared with those from the HPV group included in the NCT00779766 study (aged 18-25 years).
Detailed description
This Protocol Posting has been updated following Protocol Amendment 1, December 2010, leading to: * The removal of 3 outcome measures * The update of 1 outcome measure
Interventions
BIOLOGICALGSK580299 (CervarixTM)
3-dose schedule intramuscularly vaccination (Months 0, 1 and 6)
BIOLOGICALEngerix-BTM
3-dose schedule intramuscularly vaccination (Months 0, 1 and 6)
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
26 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Written informed consent prior to study enrolment. * Healthy adult females from Chinese origin and residing in China between and including 26 and 45 years of age at the time of the first vaccination. * Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. * Healthy subjects as established by medical history and history-directed clinical examination before entering into the study. * Subjects must not be pregnant. Absence of pregnancy will be verified with a urine pregnancy test before each vaccination. Subjects must be of non-childbearing potential, i.e., have a current tubal ligation, hysterectomy, ovariectomy, be one year post-menopausal, or if of childbearing potential, they must be abstinent or have practiced adequate contraception for 30 days prior to vaccination, have a negative pregnancy test on the day of vaccination and agree to continue such precautions during the entire treatment period and for 2 months after completion of the vaccination series.
Exclusion criteria
* Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period. * 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 the first dose of vaccine. * 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). * 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 subjects must be at least three months post-pregnancy and not breastfeeding to enter the study. * Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the protocol during the study period. * Previous administration of 3-O-desacyl-4'-monophosphoryl lipid A or AS04 adjuvant. * Previous vaccination against hepatitis B or planned administration of any hepatitis B vaccine other than that foreseen by the study protocol during the study period. * History of hepatitis B infection. * Known exposure to hepatitis B within the previous 6 weeks. * History of chronic condition(s) requiring treatment such as cancer or autoimmune disease. * History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the vaccine (e.g. aluminium). * Hypersensitivity to latex. * 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 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 Seroconverted Subjects Against Human Papillomavirus-16 (HPV-16) and HPV-18 | One month after third vaccination (Month 7) | A seroconverted subject was defined as a subject seronegative at baseline whose concentration for anti-HPV-16/18 antibodies, as measured by Enzyme-linked Immunosorbent assay (ELISA) , was higher than or equal to (≥) cut-off value. A seronegative subject was defined as a subject whose antibody concentration was below (\<) cut-off value. Cut-off values were 8 ELISA units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations for Anti-HPV-16 and Anti-HPV-18 Antibodies | Before vaccination (Month 0) and one month after third vaccination (Month 7) | Concentrations are given as geometric mean titers (GMTs), expressed in ELISA units per milliliter (EL.U/mL). Cut-off values were 8 EL.U/mL for anti-HPV-16 antibodies, and 7 EL.U/mL for anti-HPV-18 antibodies. |
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | During the 7 days (Days 0 - 6) after any vaccination | Solicited local symptoms assessed were pain, redness and swelling. Grade 3 redness and swelling were redness and swelling above 50 millimeters (mm) and grade 3 pain was defined as pain that prevented normal activity. Any was defined as the incidence of a symptom regardless of intensity grade. |
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | During the 7 days (Days 0 - 6) after any vaccination | Solicited symptoms were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and temperature \[axillary temperature above (\>)37 degrees Celsius(°C)\].Grade 3 temperature= temperature \>39°C. Grade 3 utricaria= distributed on at least 4 body areas. Grade 3 symptom=prevented normal activity. Gastrointestinal symptoms=nausea, vomiting, diarrhoea and/or abdominal pain. Arthralgia (joint pain): in joints distal from injection site. Any=incidence of a symptom regardless of intensity grade or relationship to vaccination. Related = incidence of a symptom assessed by investigator as related to vaccination. |
| Number of Subjects Seropositive Against HPV-16 and HPV-18 | Before vaccination (Month 0) and one month after third vaccination (Month 7) | A seropositive subject was defined as a subject whose anti-HPV-16/18 antibody concentration, as measured by ELISA, was higher than or equal to (≥) cut-off value. Cut-off values were 8 ELISA 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 Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | Within 30 days (Days 0 - 29) after any vaccination | An unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 was an event that prevented normal activities and related was defined as an unsolicited AE assessed by the investigator to be causally related to the study vaccination. |
| Number of Subjects Reporting Medically Significant Conditions (MSCs) Including Potential Immune Mediated Diseases (pIMDs) | Throughout the study (from Month 0 up to Month 12) | MSCs were AEs prompting emergency room or physician visits that were not related to common diseases (upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury), or not related to routine visits for physical examination or vaccination. It also included SAEs not related to common diseases. MSCs included pIMDs, a subset of MSCs that included autoimmune diseases and other inflammatory and/or neurological disorders of interest which might or might not have had an autoimmune etiology. |
| Number of Subjects With Outcome of Pregnancies | Throughout the study (from Month 0 up to Month 12) | The sole pregnancy outcome reported was elective termination with no apparent congenital anomaly. |
| Number of Subjects Reporting Any, Grade 3 and Related Serious Adverse Events (SAEs) | Throughout the study (from Month 0 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. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination, grade 3 was a SAE that prevented normal activities, and related was defined as a SAE assessed by the investigator to be causally related to the study vaccination. and related was an event assessed by the investigator as causally related to the study vaccination. |
Countries
China
Participant flow
Pre-assignment details
The study comprised a Primary Vaccination Phase from Day 0 to Month 7, followed by a Long-Term Safety Follow-up Phase, up to Month 12.
Participants by arm
| Arm | Count |
|---|---|
| Cervarix Group Subjects received a 3-dose vaccination course of the Cervarix™ vaccine administered intramuscularly in the deltoid region of the non-dominant arm according to a 0, 1, 6-month schedule. | 606 |
| Engerix Group Subjects received a 3-dose vaccination course of the Engerix™-B vaccine administered intramuscularly in the deltoid region of the non-dominant arm according to a 0, 1, 6-month schedule. | 606 |
| Total | 1,212 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Cervarix Group | Engerix Group | Total |
|---|---|---|---|
| Age, Continuous | 35.8 Years STANDARD_DEVIATION 4.92 | 35.6 Years STANDARD_DEVIATION 5.06 | 35.7 Years STANDARD_DEVIATION 4.99 |
| Sex: Female, Male Female | 606 Participants | 606 Participants | 1212 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 | 490 / 606 | 318 / 606 |
| serious Total, serious adverse events | 3 / 606 | 3 / 606 |
Outcome results
Primary
Number of Seroconverted Subjects Against Human Papillomavirus-16 (HPV-16) and HPV-18
A seroconverted subject was defined as a subject seronegative at baseline whose concentration for anti-HPV-16/18 antibodies, as measured by Enzyme-linked Immunosorbent assay (ELISA) , was higher than or equal to (≥) cut-off value. A seronegative subject was defined as a subject whose antibody concentration was below (\<) cut-off value. Cut-off values were 8 ELISA 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 third vaccination (Month 7)
Population: The analysis was based on the according-to-protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Seroconverted Subjects Against Human Papillomavirus-16 (HPV-16) and HPV-18 | HPV-16 | 345 Participants |
| Cervarix Group | Number of Seroconverted Subjects Against Human Papillomavirus-16 (HPV-16) and HPV-18 | HPV-18 | 363 Participants |
| Engerix Group | Number of Seroconverted Subjects Against Human Papillomavirus-16 (HPV-16) and HPV-18 | HPV-16 | 67 Participants |
| Engerix Group | Number of Seroconverted Subjects Against Human Papillomavirus-16 (HPV-16) and HPV-18 | HPV-18 | 135 Participants |
Secondary
Concentrations for Anti-HPV-16 and Anti-HPV-18 Antibodies
Concentrations are given as geometric mean titers (GMTs), expressed in ELISA units per milliliter (EL.U/mL). Cut-off values were 8 EL.U/mL for anti-HPV-16 antibodies, and 7 EL.U/mL for anti-HPV-18 antibodies.
Time frame: Before vaccination (Month 0) and one month after third vaccination (Month 7)
Population: The analysis was based on the according-to-protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | Concentrations for Anti-HPV-16 and Anti-HPV-18 Antibodies | HPV-16, Day 0 | 9.7 EL.U/mL |
| Cervarix Group | Concentrations for Anti-HPV-16 and Anti-HPV-18 Antibodies | HPV-16, Month 7 | 6439.8 EL.U/mL |
| Cervarix Group | Concentrations for Anti-HPV-16 and Anti-HPV-18 Antibodies | HPV-18, Day 0 | 6.4 EL.U/mL |
| Cervarix Group | Concentrations for Anti-HPV-16 and Anti-HPV-18 Antibodies | HPV-18, Month 7 | 3563.3 EL.U/mL |
| Engerix Group | Concentrations for Anti-HPV-16 and Anti-HPV-18 Antibodies | HPV-18, Month 7 | 8.7 EL.U/mL |
| Engerix Group | Concentrations for Anti-HPV-16 and Anti-HPV-18 Antibodies | HPV-16, Day 0 | 9.3 EL.U/mL |
| Engerix Group | Concentrations for Anti-HPV-16 and Anti-HPV-18 Antibodies | HPV-18, Day 0 | 6.0 EL.U/mL |
| Engerix Group | Concentrations for Anti-HPV-16 and Anti-HPV-18 Antibodies | HPV-16, Month 7 | 12.1 EL.U/mL |
Secondary
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms
Solicited local symptoms assessed were pain, redness and swelling. Grade 3 redness and swelling were redness and swelling above 50 millimeters (mm) and grade 3 pain was defined as pain that prevented normal activity. Any was defined as the incidence of a symptom regardless of intensity grade.
Time frame: During the 7 days (Days 0 - 6) after any vaccination
Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented and symptom sheet completed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Any pain | 470 Participants |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Grade 3 pain | 36 Participants |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Any redness | 156 Participants |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Grade 3 redness | 2 Participants |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Any swelling | 146 Participants |
| Cervarix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Grade 3 swelling | 11 Participants |
| Engerix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Any swelling | 58 Participants |
| Engerix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Any pain | 296 Participants |
| Engerix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Grade 3 redness | 1 Participants |
| Engerix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Grade 3 pain | 5 Participants |
| Engerix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Grade 3 swelling | 1 Participants |
| Engerix Group | Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Any redness | 88 Participants |
Secondary
Number of Subjects Reporting Any, Grade 3 and Related Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination, grade 3 was a SAE that prevented normal activities, and related was defined as a SAE assessed by the investigator to be causally related to the study vaccination. and related was an event assessed by the investigator as causally related to the study vaccination.
Time frame: Throughout the study (from Month 0 up to Month 12)
Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Serious Adverse Events (SAEs) | Any SAE(s) | 3 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Serious Adverse Events (SAEs) | Grade 3 SAE(s) | 2 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Serious Adverse Events (SAEs) | Related SAE(s) | 0 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Serious Adverse Events (SAEs) | Any SAE(s) | 3 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Serious Adverse Events (SAEs) | Grade 3 SAE(s) | 0 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Serious Adverse Events (SAEs) | Related SAE(s) | 0 Participants |
Secondary
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms
Solicited symptoms were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and temperature \[axillary temperature above (\>)37 degrees Celsius(°C)\].Grade 3 temperature= temperature \>39°C. Grade 3 utricaria= distributed on at least 4 body areas. Grade 3 symptom=prevented normal activity. Gastrointestinal symptoms=nausea, vomiting, diarrhoea and/or abdominal pain. Arthralgia (joint pain): in joints distal from injection site. Any=incidence of a symptom regardless of intensity grade or relationship to vaccination. Related = incidence of a symptom assessed by investigator as related to vaccination.
Time frame: During the 7 days (Days 0 - 6) after any vaccination
Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented and symptom sheet completed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Any gastrointestinal symptoms | 33 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Grade 3 arthralgia | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related arthralgia | 17 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Any fatigue | 100 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Grade 3 fatigue | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related fatigue | 93 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Any arthralgia | 19 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Grade 3 gastrointestinal symptoms | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related gastrointestinal symptoms | 24 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Any headache | 71 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Grade 3 headache | 4 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related headache | 64 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Any myalgia | 69 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Grade 3 myalgia | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related myalgia | 66 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Any rash | 2 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Grade 3 rash | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related rash | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Temperature >37.0°C | 28 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Temperature >39.0°C | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related temperature | 15 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Any urticaria | 4 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Grade 3 urticaria | 2 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related urticaria | 3 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Grade 3 urticaria | 0 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Any arthralgia | 14 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Any myalgia | 42 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Grade 3 arthralgia | 0 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Temperature >37.0°C | 24 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related arthralgia | 12 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Grade 3 myalgia | 0 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Any fatigue | 68 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Any urticaria | 1 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Grade 3 fatigue | 1 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related myalgia | 39 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related fatigue | 59 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Temperature >39.0°C | 0 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Any gastrointestinal symptoms | 24 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Any rash | 1 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Grade 3 gastrointestinal symptoms | 0 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related urticaria | 1 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related gastrointestinal symptoms | 11 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Grade 3 rash | 0 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Any headache | 46 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related temperature | 13 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Grade 3 headache | 0 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related rash | 1 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Related headache | 38 Participants |
Secondary
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
An unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 was an event that prevented normal activities and related was defined as an unsolicited AE assessed by the investigator to be causally related to the study vaccination.
Time frame: Within 30 days (Days 0 - 29) after any vaccination
Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | Any AE(s) | 32 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | Grade 3 AE(s) | 2 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | Related AE(s) | 0 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | Any AE(s) | 36 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | Grade 3 AE(s) | 2 Participants |
| Engerix Group | Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | Related AE(s) | 1 Participants |
Secondary
Number of Subjects Reporting Medically Significant Conditions (MSCs) Including Potential Immune Mediated Diseases (pIMDs)
MSCs were AEs prompting emergency room or physician visits that were not related to common diseases (upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury), or not related to routine visits for physical examination or vaccination. It also included SAEs not related to common diseases. MSCs included pIMDs, a subset of MSCs that included autoimmune diseases and other inflammatory and/or neurological disorders of interest which might or might not have had an autoimmune etiology.
Time frame: Throughout the study (from Month 0 up to Month 12)
Population: The analysis was performed on the Total Vaccinated cohort which included all subjects with at least one vaccine administration documented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix Group | Number of Subjects Reporting Medically Significant Conditions (MSCs) Including Potential Immune Mediated Diseases (pIMDs) | 5 Participants |
| Engerix Group | Number of Subjects Reporting Medically Significant Conditions (MSCs) Including Potential Immune Mediated Diseases (pIMDs) | 7 Participants |
Secondary
Number of Subjects Seropositive Against HPV-16 and HPV-18
A seropositive subject was defined as a subject whose anti-HPV-16/18 antibody concentration, as measured by ELISA, was higher than or equal to (≥) cut-off value. Cut-off values were 8 ELISA units per milliliter (EL.U/mL) for anti-HPV-16 antibodies, and 7 EL.U/mL for anti-HPV-18 antibodies.
Time frame: Before vaccination (Month 0) and one month after third vaccination (Month 7)
Population: The analysis was based on the according-to-protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Seropositive Against HPV-16 and HPV-18 | HPV-16, Day 0 | 251 Participants |
| Cervarix Group | Number of Subjects Seropositive Against HPV-16 and HPV-18 | HPV-16, Month 7 | 596 Participants |
| Cervarix Group | Number of Subjects Seropositive Against HPV-16 and HPV-18 | HPV-18, Day 0 | 231 Participants |
| Cervarix Group | Number of Subjects Seropositive Against HPV-16 and HPV-18 | HPV-18, Month 7 | 594 Participants |
| Engerix Group | Number of Subjects Seropositive Against HPV-16 and HPV-18 | HPV-18, Month 7 | 312 Participants |
| Engerix Group | Number of Subjects Seropositive Against HPV-16 and HPV-18 | HPV-16, Day 0 | 257 Participants |
| Engerix Group | Number of Subjects Seropositive Against HPV-16 and HPV-18 | HPV-18, Day 0 | 200 Participants |
| Engerix Group | Number of Subjects Seropositive Against HPV-16 and HPV-18 | HPV-16, Month 7 | 322 Participants |
Secondary
Number of Subjects With Outcome of Pregnancies
The sole pregnancy outcome reported was elective termination with no apparent congenital anomaly.
Time frame: Throughout the study (from Month 0 up to Month 12)
Population: The analysis was performed on Total Vaccinated cohort, which included all subjects with at least one vaccine administration documented, solely on subjects with outcome of pregnancies.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix Group | Number of Subjects With Outcome of Pregnancies | 4 Participants |
| Engerix Group | Number of Subjects With Outcome of Pregnancies | 1 Participants |