Immunogenicity and Safety of GSK Biologicals' HPV Vaccine 580299 in Healthy Japanese Females 10-15 Years of Age

Study Overview
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Brief Summary
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Human papillomavirus (HPV) infection has been established as a necessary cause of cervical cancer. GSK Biologicals has developed an HPV vaccine (580299) which targets the 2 most common oncogenic HPV types (HPV-16 and HPV-18), found in approximately 70% of all cervical cancers. In previous trials, the vaccine has been found to be efficacious in the prevention of incident and persistent HPV-16/18 infections and associated cytological abnormalities. HPV vaccination should ideally be performed before onset of sexual activity. Previous studies showed that GSK Biologicals' HPV vaccine 580299 is safe and immunogenic when administered to European, Asian, Latin American and Australian pre-adolescents and adolescents. Here, we aim to assess the immunogenicity and safety of the GSK Biologicals' HPV vaccine 580299 in healthy Japanese pre-adolescent and adolescent female subjects aged 10-15 years. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
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Evaluation of the Immunogenicity and Safety of GlaxoSmithKline Biologicals' HPV Vaccine 580299 When Administered as a 3-dose Schedule in Healthy Japanese Pre-adolescent and Adolescent Female Subjects.

Conditions
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Infections, Papillomavirus

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator/co-investigator believes that they and/or their parent(s)/legally acceptable representative(s) can and will comply with the requirements of the protocol should be enrolled in the study. A Japanese female between, and including, 10 and 15 years of age at the time of the first vaccination. Written informed consent obtained from the parent(s) or legally acceptable representative(s) of the subject. In addition, a written informed assent must be obtained from the subject prior to enrolment. Healthy subjects as established by medical history and history-directed clinical examination before entering into the study. All subjects must have a negative urine pregnancy test. Subjects must be of non-childbearing potential, or, if of childbearing potential, they must be abstinent or have used adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series. Non-abstinent pre-menarche subjects, as well as subjects who reach menarche during study, must follow the same precautions. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine 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 or planned during study. 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 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. Concurrently participating in another clinical study, at any time during the study period (up to Month 7), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). Previous vaccination against HPV, or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period (Day 0 to Month 7). Previous administration of components of the investigational vaccine . Cancer or autoimmune disease under treatment. 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. Hypersensitivity to latex. Acute disease at the time of enrolment. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory tests. 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. Pregnant or breastfeeding subject. Subject planning to become pregnant or planning to discontinue contraceptive precautions. Oral temperature ≥ 37.5°C/Axillary temperature ≥ 37.5°C.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 15 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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) | 
| Anti-HPV-16 and Anti-HPV-18 Antibody Titers | Titers are given as geometric mean titers (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. | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Other Medically Significant Conditions | NOCDs assessed include e.g. autoimmune disorders, asthma, type I diabetes. Medically significant conditions assessed include adverse events prompting emergency room visits and physician office visits not related to common illnesses or Serious Adverse Events that are not related to common illnesses. | From Day 0 up to Month 7 | 
| Outcome of All Pregnancies | According to the study protocol, the outcome of all pregnancies reported during the entire study period was to be reported, even if delivery occurs after the end of the study. | Up to Month 7 | 
| Number of Subjects Reporting Serious Adverse Events (SAEs) | Serious adverse events 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. | From Day 0 up to Month 7 | 
| Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Parameters | Abnormalities include values outside (above or below) the normal ranges. Normal ranges: alanine aminotransferase (ALT): 5-35 U/L aspartate aminotransferase (AST): 5-50 U/L basophils: 0-2 % bilirubin total: 0.1-1.1 mg/dL blood urea nitrogen: 0-20 mg/dL creatinine: 0.2-1.2 mg/dL eosinophils: 0-7 % hematocrit: 30-45 % hemoglobin: 10-15 g/dL lymphocytes: 18-50 % monocytes: 1-8 % neutrophils: 42-74 % platelets: 10-60 10E4/microL red blood cells: 350-550 10E4/microL total protein: 6.5-8.6 g/dL white blood cells: 4000-15000 /microL | At Day 0 and Month 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, Human Papillomavirus (HPV) vaccine, cervical cancer, immunogenicity, vaccine, viral infections, pre-adolescent and adolescent females