Human Papillomavirus (HPV) Vaccine Consistency and Non-inferiority Trial in Young Adult Women

Study Overview
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Brief Summary
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The study will be extended for subjects who received all three doses of vaccine in Finland, Denmark and Estonia to determine long-term safety and immunogenicity of the HPV-16/18 vaccine. Human Papilloma virus (HPV) are viruses that cause a common infection of the skin and genitals in men and women. Several types of HPV infection are transmitted by sexual activity and, in women, can infect the cervix (part of the uterus or womb). This infection often goes away by itself, but if it does not go away (this is called persistent infection), it can lead in women over a long period of time to cancer of the cervix. If a woman is not infected by HPV, it is very unlikely that she will get cervical cancer. This study will evaluate the consistency of consecutive vaccine lots and the non-inferiority of modified manufacturing processes of GlaxoSmithKline Biologicals HPV-16/18 vaccine and the vaccine safety, over 12 months, in young adolescents and women of 10-25 years of age at study start.

Detailed Description
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Approximately 750 study subjects received different lots of the HPV vaccine administered intramuscularly according to a 0-1-6 month schedule. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
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A Long-term, Open, Follow-up of the Immunogenicity and Safety of GlaxoSmithKline Biologicals' HPV-16/18 L1/AS04 Vaccine in Healthy Female Subjects Vaccinated Either Pre- or Post-menarche in the Primary Study

Conditions
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Papillomavirus Type 16/18 Infection, Cervical Intraepithelial Neoplasia

Intervention / Treatment
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* Biological: Cervarix™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A female who enrolled in the HPV-012 (NCT00337818) study in Denmark, Estonia and Finland, received three doses of vaccine and completed Visit 4 (Month 7). Written informed consent obtained from the subject prior to enrolment (for subjects below the legal age of consent, written informed consent must be obtained from a parent or legally acceptable representative (LAR) and, in addition, the subject must sign and personally date a written informed assent). Exclusion criteria Use of any investigational or non-registered product (drug or vaccine) or planned use during the study period. 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). Chronic administration of immunosuppressants or other immune-modifying drugs occurring less than three months prior to blood sampling. Administration of immunoglobulins and/or any blood products within the three months preceding blood sampling.

Ages Eligible for Study
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Minimum Age: 10 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 New Process<br>Subjects aged 15 to 25 years received 3 doses (at Months 0, 1 and 6) of Cervarix™ (human papillomavirus [HPV]) produced with the new manufacturing process. | Biological: Cervarix™<br>* Three doses of vaccine according to a 0, 1, 6 month schedule (during the primary study)<br>|
| Experimental: Cervarix Old Process Group<br>Subjects aged 15 to 25 years who received 3 doses (at Months 0, 1 and 6) of Cervarix™ (human papillomavirus [HPV]) produced with the old manufacturing process. | Biological: Cervarix™<br>* Three doses of vaccine according to a 0, 1, 6 month schedule (during the primary study)<br>|
| Experimental: Cervarix Young/Lot 1 Group<br>Subjects aged 10 to 14 years, who received 3 doses (at Months 0, 1 and 6) of Cervarix™ (human papillomavirus [HPV]) produced with the new manufacturing process (Lot 1). | Biological: Cervarix™<br>* Three doses of vaccine according to a 0, 1, 6 month schedule (during the primary study)<br>|

What is the study measuring?
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Primary 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). *Data for Month 18 outcome variables were incorporated into the Month 24 analyses. | At months 18*, 24, 36 and 48 | 

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 in Cervical Samples | Titers are given as Geometric Mean Titers (GMTs) expressed as EL.U/mL. | At months 24, 36, and 48 | 
| Titers of Anti-HPV-16 and Anti-HPV-18 Immunoglobulin G (IgG) Antibodies in Blood Samples | Titers are given as Geometric Mean Titers (GMTs) expressed as EL.U/mL. | At Months 24, 36 and 48 | 
| Number of Subjects Reporting Pregnancies, New Onset Chronic Diseases (NOCDs) and Other Medically Significant Conditions (MSCs) | NOCDs assessed include e.g. autoimmune disorders, asthma, type I diabetes. MSCs assessed include adverse events prompting emergency room or physician visits that are not related to common diseases or serious adverse events (SAEs) that are not related to common diseases. | Throughout the study period (up to Month 48) | 
| Number of Subjects Reporting 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. | Throughout the study period (up to Month 48) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-inferiority, Immunogenicity, HPV Vaccine Consistency