Study to Evaluate the Immune Response and Safety of GSK Biologicals' HPV Vaccine in Healthy Women Aged 18-35 Years

Study Overview
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Brief Summary
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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 HPV-16/18 L1 VLP AS04 vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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The protocol was primarily amended for the following reasons: Merck's tetravalent HPV vaccine, Gardasil®, has been licensed and is now becoming commercially available in an increasing number of countries. Therefore, the study procedures were revised to include questions at every visit to determine if subjects have received an HPV vaccine outside of the study. It was decided to offer GSK Biologicals' HPV vaccine to all subjects in the control group at the end of the study. The HPV vaccine will be offered to these subjects based on its local indication once the vaccine is marketed in Malaysia.

Official Title
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Phase 3, Open, Age-stratified Study to Assess Immunogenicity and Safety of GSK Biologicals' HPV-16/18 Vaccine Administered Intramuscularly According to 3-dose Schedule (0,1,6 Months) in Healthy Female Subjects Aged 15 - 55 Years and Long Term Follow-up

Conditions
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Infections, Papillomavirus

Intervention / Treatment
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* Biological: Placebo
* Biological: HPV-16/18 L1 VLP AS04 (Cervarix TM)


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 from Malaysia between, and including, 18 and 35 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 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 an effective method of birth control 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 vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. 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. 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 confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s). Hypersensitivity to latex. Acute disease at the time of enrolment. 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 vaccine(s) or planned administration during the study period. Enrolment will be deferred until the subject is outside of specified window. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cervarix Group<br>Subjects received 3 doses of HPV-16/18 L1 VLP AS04 (Cervarix™) according to a 0, 1, 6-month schedule. | Biological: HPV-16/18 L1 VLP AS04 (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>Subjects received 3 doses of Placebo according to a 0, 1, 6-month schedule. | Biological: Placebo<br>* Three doses of vaccine administered intramuscularly according to a 0, 1, 6-month schedule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who 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 antibodies with titers greater than or equal to the predefined cut-off value in the serum of subjects 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. | At Month 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL). | At Month 0 and Month 7 | 
| Number of Subjects Reporting Solicited Symptoms | Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include arthralgia, fatigue, fever, gastro-intestinal symptoms, headache, myalgia, rash and urticaria. | During the 7 days after each vaccination | 
| Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 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. | Within 30 days after any vaccination | 
| Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (AEs) | NOCDs assessed include e.g. autoimmune disorders, asthma, type I diabetes, allergies,... Medically significant AEs assessed include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or SAEs that are not related to common diseases. | Throughout the study period (up to Month 7) | 
| Number of Subjects Reporting Serious Adverse Events | Serious adverse events assessed include medical occurrences that results 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. | Throughout the study period (up to Month 7) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV-16/18 L1 VLP AS04, Cervical neoplasia, Cervical cancer, Human Papillomavirus (HPV), Double-blind, AS04