Safety and Protective Effect Study of GSK Biologicals' Human Papillomavirus (Types 16, 18) Vaccine, Adsorbed (GSK580299) in Healthy Female Subjects From the HPV-039 Study
Condition: Cervical Intraepithelial Neoplasia
MeSH terms: Uterine Cervical Dysplasia
Intervention: HPV (Types 16, 18) Vaccine, Adsorbed
Intervention description: Three doses of Human Papillomavirus (Types 16, 18) Vaccine, Adsorbed administered intramuscularly in the deltoid region of the upper arm, according to a 0, 1, 6-month schedule.
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 3537.0
Sex: Female
Minimum age: 26 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Adults; Human Papillomavirus (HPV); Cervical cancer; Safety

Summary:

      This study was designed to enable all subjects who received placebo in the HPV-039 study
      (NCT00779766), to also receive GSK Biologicals' Human Papillomavirus (Types 16, 18) Vaccine,
      Adsorbed. Safety data in terms of serious adverse events (SAEs), any adverse events
      (AEs)/SAEs leading to premature discontinuation of the study, potential immune mediated
      diseases (pIMDs) and pregnancies (and their outcomes) were collected during the study period.

      In addition, this study assessed the long term protective effect of the vaccine, in an
      exploratory manner, in terms of rates of HPV-related (vaccine type) incident cervical
      infection up to approximately 10 years after vaccination in subjects who participated in
      HPV-039 study (NCT00779766).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects who, in the opinion of the investigator, can and will comply with the
             requirements of the protocol.

          -  Written informed consent obtained from the subject prior to performing any study
             specific procedure.

          -  Subjects previously enrolled in the HPV-039 study.

          -  Subjects with negative pregnancy test at Visit 1.

        Additional inclusion criteria for subjects of HPV group undergoing vaccination ONLY:

          -  Healthy subjects as established by medical history and clinical examination before
             entering into the study.

          -  Female subjects of non-childbearing potential may be enrolled in the study.

               -  Non-childbearing potential is defined as pre-menarche, current bilateral tubal
                  ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.

          -  Female subjects of childbearing potential may be enrolled in the study, if the
             subject:

               -  has practiced adequate contraception for 30 days prior to vaccination, and

               -  has a negative pregnancy test on the day of vaccination, and

               -  has agreed to continue adequate contraception during the entire treatment period
                  and for 2 months after completion of the vaccination series.

        Exclusion Criteria:

          -  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 vaccine/product (pharmaceutical product or device).

          -  Previous vaccination against HPV outside of study HPV-039.

        Additional exclusion criteria for subjects of HPV group undergoing vaccination ONLY:

          -  Use of any investigational or non-registered product other than the study vaccine
             during the period starting 30 days before the first dose of study vaccine, or planned
             use during the study period.

          -  Any medical condition that in the judgment of the investigator would make
             intramuscular injection unsafe.

          -  Chronic administration of immunosuppressants or other immune-modifying drugs during
             the period starting six months prior to the first vaccine dose. For corticosteroids,
             this will mean prednisone. Inhaled and topical steroids are allowed.

          -  Planned administration/administration of a vaccine/product not foreseen by the study
             protocol in the period starting 30 days before and after each dose of vaccine
             administration, with the exception of administration of routine vaccines e.g.
             meningococcal, hepatitis B, hepatitis A, inactivated influenza up to eight days before
             and after each dose of study vaccine. Enrolment will be deferred until the subject is
             outside of the specified window.

          -  Any confirmed or suspected immunosuppressive or immunodeficient condition, based on
             medical history and physical examination.

          -  History of any reaction or hypersensitivity likely to be exacerbated by any component
             of the vaccine.

          -  Previous administration of MPL or AS04 adjuvant.

          -  Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal
             functional abnormality, as determined by physical examination or laboratory screening
             tests.

          -  Cancer or autoimmune disease under treatment.

          -  Hypersensitivity to latex.

          -  Acute disease and/or fever at the time of enrolment.

               -  Fever is defined as temperature ≥37.0°C. The preferred location for measuring
                  temperature in this study will be the axilla.

               -  Subjects with a minor illness without fever may be enrolled at the discretion of
                  the investigator.

          -  Pregnant or breastfeeding. Subjects must be at least three months post-pregnancy and
             not breastfeeding to enter the study.

          -  Females planning to become pregnant or planning to discontinue contraceptive
             precautions during the vaccination phase of the study, i.e. up to two months after the
             last vaccine dose.