Study to Assess Immune Responses and Safety of the GSK-580299 Vaccine in Healthy Women (26 to 45 Years)

Study Overview
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Brief Summary
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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
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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

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' HPV Vaccine (GSK 580299) in Healthy Adult Chinese Female Subjects

Conditions
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Infections, Papillomavirus

Intervention / Treatment
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* Biological: GSK580299 (CervarixTM)
* Biological: Engerix-BTM


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 26 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cervarix Group<br>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. | Biological: GSK580299 (CervarixTM)<br>* 3-dose schedule intramuscularly vaccination (Months 0, 1 and 6)<br>|
| Active Comparator: Engerix Group<br>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. | Biological: Engerix-BTM<br>* 3-dose schedule intramuscularly vaccination (Months 0, 1 and 6)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | One month after third vaccination (Month 7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Before vaccination (Month 0) and one month after third vaccination (Month 7) | 
| 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. | Before vaccination (Month 0) and one month after third vaccination (Month 7) | 
| 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. | During the 7 days (Days 0 - 6) after any vaccination | 
| 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. | During the 7 days (Days 0 - 6) after any vaccination | 
| 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. | Throughout the study (from Month 0 up to Month 12) | 
| 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. | Within 30 days (Days 0 - 29) after any vaccination | 
| 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. | Throughout the study (from Month 0 up to Month 12) | 
| Number of Subjects With Outcome of Pregnancies | The sole pregnancy outcome reported was elective termination with no apparent congenital anomaly. | Throughout the study (from Month 0 up to Month 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, HPV vaccine, Immune response, Human papillomavirus, China