A Study to Evaluate the Immune Response and Safety of GSK Biologicals' HPV-16/18 L1 VLP AS04 Vaccine/Cervarix TM Vaccine in Healthy Females Aged 15-25 Years

Study Overview
=================
Brief Summary
-----------------
Human papillomavirus infection has clearly been recognized as the cause of cervical cancer. The infection of the cervix by certain oncogenic types of HPV, if not cleared, can lead to cervical cancer in women. This study will evaluate the immunogenicity and safety of the GSK Biologicals' HPV-16/18 L1 VLP AS04 vaccine (Cervarix TM) vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
-----------------
A Phase IIIb, Double-blind, Randomized, Controlled Study to Evaluate the Immunogenicity and Safety of GlaxoSmithKline Biologicals' HPV-16/18 L1 VLP AS04 Vaccine, Administered Intramuscularly in Healthy Female Subjects Aged 15 - 25 Years

Conditions
-----------------
Infections, Papillomavirus

Intervention / Treatment
-----------------
* Biological: HPV-16/18 VLP/AS04 vaccine (Cervarix TM)
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects who the investigator believes that they or their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study. A female between, and including, 15 and 25 years of age at the time of the first vaccination. Written informed assent obtained from the subject and informed consent obtained from the parent or guardian of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Subjects must have a negative urine pregnancy test. Subjects of childbearing potential at the time of study entry must be abstinent, or must be using adequate contraceptive precautions for 30 days prior to vaccination and must agree to continue such precautions for two months after completion of the vaccination series. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study/ control vaccine within 30 days preceding the first dose of study/ control vaccine, or planned use during the study period. Pregnant or breastfeeding. Planning to become pregnant or likely to become pregnant. Chronic administration (defined as more than 14 days) 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. However, the 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. Previous administration of components of the investigational vaccine Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period. Any medically diagnosed or suspected immunodeficient condition such as HIV infection based on medical history and physical examination. History of thrombocytopenia or hemostatic disorder in which case the study vaccine should under no circumstances be administered intramuscularly. History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study/control vaccines. Hypersensitivity to latex. Known acute or chronic, clinically significant neurologic, pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests. History of chronic condition(s) requiring treatment. Administration of immunoglobulins and/or any blood product within three months preceding the first dose of study/control vaccine or planned administration during the study period. Enrolment will be deferred until the subject is outside of specified window. Acute disease at the time of enrolment.

Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Maximum Age: 25 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cervarix Group<br> | Biological: HPV-16/18 VLP/AS04 vaccine (Cervarix TM)<br>* Three doses of vaccine administered intramuscularly according to a 0, 1, 6-month schedule.<br>* Other names: GSK Biologicals' HPV-16/18 VLP/AS04 vaccine;|
| Placebo Comparator: Placebo Group<br> | Biological: Placebo<br>* Three doses of placebo administered intramuscularly according to a 0, 1, 6-month schedule.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Seroconversion is defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the sera of subjects seronegative before vaccination. Cut-off values were 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. | One month post Dose 3 (Month 7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-HPV-16 and Anti-HPV-18 Antibody Titres | Titres are given as geometric mean titres (GMTs) calculated on all subjects. | Before vaccination (PRE) and one month post Dose 3 (Month 7) | 
| Number of Subjects Reporting Solicited Local Symptoms | Solicited local symptoms assessed include pain, redness and swelling at the injection site. | During the 7-day (Days 0-6) period following each vaccination | 
| Number of Subjects Reporting Solicited General Symptoms | Solicited general symptoms assessed include arthralgia, fatigue, fever, gastrointestinal symptoms, headache, myalgia, rash, and urticaria. | During the 7-day (Days 0-6) period following each vaccination | 
| Number of Subjects Reporting Unsolicited Adverse Events (AE) | 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. | During the 30-day (Days 0-29) period following each vaccination | 
| Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions | NOCDs assessed include e.g. autoimmune disorders, asthma, type I diabetes. Medically significant AEs assessed include AEs prompting emergency room visits and physician office visits not related to common illnesses or Serious Adverse Events (SAEs) that are not related to common illnesses. | From Day 0 up to Month 7 | 
| Number of Subjects Reporting Serious Adverse Events (SAE) | Serious adverse events assessed include medical occurrences that result in death, is 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. | From Day 0 up to Month 7 | 
| Number of Subjects With Pregnancies and Their Outcome | Total: the total number of pregnancies in a group. The specific outcomes are also listed. | from Day 0 up to Month 7 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cervical neoplasia, AS04, Randomized, Cervical cancer, HPV-16/18 L1 VLP AS04, Phase IIIb, Korea, HPV, Double-blind, Controlled