Immunogenicity and Safety of a Commercially Available Vaccine Co-administered With GSK HPV Vaccine (580299)

Study Overview
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Brief Summary
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Infection with human papillomavirus (HPV) has been clearly established as the necessary cause of cervical cancer. The current Phase 3b study is designed to assess the immunogenicity and safety of a commercially available vaccine co-administered with GlaxoSmithKline Biologicals' HPV vaccine GSK580299 in healthy female subjects.

Official Title
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Evaluation of the Immunogenicity and Safety of a Commercially Available Vaccine When Co-administered With GlaxoSmithKline Biologicals' HPV Vaccine (580299) in Healthy Female Subjects.

Conditions
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Infections, Papillomavirus, Papillomavirus Vaccines

Intervention / Treatment
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* Biological: Subjects received 3 doses of GSK Biologicals' HPV vaccine (580299) (Cervarix™)
* Biological: Engerix™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. A female between, and including, 20 and 25 years of age at the time of the first vaccination. Written informed consent obtained from the subject. Healthy subjects as established by medical history and history directed clinical examination before entering into the study. Subjects must not be pregnant. Subjects 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 continue such precautions for 2 months after completion of the vaccination series. 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. 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. Administration of routine vaccines such as meningococcal, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccines up to 8 days before the first dose of study vaccine is allowed. Concurrently participating in another clinical study, at any time during the study period (up to Month 13), 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 (as determined by the investigator) 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 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. 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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 25 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cervarix™ & Engerix™ Group<br>Subjects received 3 doses of GSK Biologicals' HPV vaccine (580299) (Cervarix™) (Months 0, 1 & 6) and 4 doses of Hepatitis B (Engerix™) vaccine (Months 0, 1, 2 & 12). | Biological: Subjects received 3 doses of GSK Biologicals' HPV vaccine (580299) (Cervarix™)<br>* Intramuscular administration, 3 doses.<br>* Other names: GSK Biologicals' HPV vaccine 580299;Biological: Engerix™<br>* Intramuscular administration, 4 doses.<br>* Other names: GSK Biologicals' vaccine 103860;|
| Active Comparator: Engerix™ Group<br>Subjects received 4 doses of Hepatitis B (HBV) vaccine (Months 0, 1, 2 & 12). | Biological: Engerix™<br>* Intramuscular administration, 4 doses.<br>* Other names: GSK Biologicals' vaccine 103860;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Seroprotected Against Hepatitis B Following 3 Doses of Engerix | A subject seroprotected against hepatitis B is a subject with anti-hepatitis B surface antigen (HBs) antibody titers greater than or equal to 10 milli-international units per milliliter (mIU/mL). | Month 3 | 
| Anti-hepatitis B Surface Antigen (HBs) Antibody Titers Following 3 Doses of Engerix | Titers are given as Geometric Mean Titers (GMTs) expressed as milli-international units per milliliter (mIU/mL). | Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 and 18 (Anti-HPV-16 and 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. | Months 2 and 7 | 
| Anti-HPV-16/18 Antibody Titers | Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL). | Months 2 and 7 | 
| Number of Subjects Seroconverted for Anti-hepatitis B (HBs) Antibodies | Anti-HBs seroconversion is defined as the appearance [i.e. titer greater than or equal to the cut-off value of 3.3 milli-international units/milliliter (mIU/mL)] of anti-HBs antibodies in the sera of subjects seronegative (with titers below the cut-off value) before vaccination. | Months 2, 3 and 13 | 
| Number of Subjects Seroprotected Against Anti-Hepatitis B (HBs) Antibodies Following 2 Doses of Engerix and After Completing the 4-dose Engerix Vaccination Course | A subject seroprotected against Hepatitis B is a subject with anti-HBs antibody titers greater than or equal to 10 mIU/mL. | Months 2 and 13 | 
| Anti-HBs Antibody Titers Following 2 Doses of Engerix and After Completing the 4-dose Engerix Vaccination Course | Titers are given as Geometric Mean Titers (GMTs) expressed as mIU/mL. | At Months 2 and 13 | 
| Number of Subjects Reporting Solicited Local Symptoms | Solicited local symptoms assessed include injection site pain, redness and swelling. Data are presented across doses. | During the 7-day period following any vaccination | 
| Number of Subjects Reporting Solicited Local Symptoms | Solicited local symptoms assessed include injection site pain, redness and swelling. Data are presented across doses. | During the 7-day period following the 4th dose of HBV vaccine | 
| Number of Subjects Reporting Solicited General Symptoms | Solicited general symptoms assessed include arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, temperature [axillary route, ≥ 37.5 degree Celsius (°C)] and urticaria. Data are presented across doses. | During the 7-day period following any vaccination | 
| Number of Subjects Reporting Solicited General Symptoms | Solicited general symptoms assessed include arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, temperature [axillary route, ≥ 37.5 degree Celsius (°C)] and urticaria. Data are presented across doses. | During the 7-day period following the 4th dose of HBV vaccine | 
| Number of Subjects Reporting Unsolicited Adverse Events | Unsolicited adverse event covers 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. | During the 30-day period following any vaccination | 
| Number of Subjects Reporting Unsolicited Adverse Events | Unsolicited adverse event covers 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. | During the 30-day period following the 4th dose of HBV vaccine | 
| 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. | Up to study end (Month 13) | 
| 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. | Up to study end (Month 13) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV, Human papillomavirus (HPV) vaccine, Hepatitis B, Cervical cancer, Papillomavirus