Efficacy Study of HPV-16/18 Vaccine (GSK 580299) to Prevent HPV-16 and/or -18 Cervical Infection in Young Healthy Women
Efficacy Study of HPV-16/18 Vaccine (GSK 580299) to Prevent HPV-16 and/or -18 Cervical Infection in Young Healthy Women
The purpose of this phase IIB MedImmune-sponsored study was to evaluate the efficacy of the
 HPV-16/18 VLP vaccine in the prevention of infection with HPV-16 and/or HPV-18 in adolescent
 and young adult women. A vaccine that prevents, or even reduces, the incidence of the common
 types of high-risk HPVs, particularly HPV-16 and HPV-18, could result in significant
 reduction in the incidence of cervical cancer and cancer-related mortality, as well as a
 reduction in the incidence of surgical procedures following abnormal Pap smears.
Inclusion Criteria:

 -  Female between and including 15 and 25 years of age at the time of screening (must not
 have reached 26th birthday)

 -  Written informed consent obtained from the subject prior to enrolment (for subjects
 below the legal age of consent, written informed consent must also be obtained from a
 parent or legal guardian of the subject)

 -  Free of obvious health problems, as established by medical history and a directed
 physical examination

 -  No more than 6 lifetime sexual partners prior to enrolment

 -  Intact uterus

 -  Subject must be of non-childbearing potential, i.e., either surgically sterilised or,
 if of childbearing potential, she must be abstinent or must be using an effective
 method of birth control for 30 days prior to vaccination, have a negative urine
 pregnancy test and must agree to continue such precautions for two months after
 completion of the vaccination series

 -  For subjects not enrolled in the HPV epidemiology study (999910/106) and for subjects
 completing the study (999910/106) >90 days prior to enrolment in the present study:
 agreement to complete both entrance and exit study questionnaires concerning general
 personal information, and sexual, contraceptive, reproductive and other gynaecological
 medical history

 -  For subjects previously enrolled in the HPV epidemiology study (and who completed the
 study and an entrance questionnaire) ≤ 90 days prior to enrolment in the present
 study: agreement to complete the exit questionnaire only.

 -  Normal cervical cytology (Pap smear) at screening, using the Cytyc ThinPrep® Pap Test.
 A normal Pap smear must also be adequate for interpretation, including the presence of
 endocervical cells; a Pap smear that is normal but inadequate for interpretation must
 be repeated as part of the protocol

 -  Seronegative for HPV-16 and HPV-18 antibody by ELISA at screening

 -  HPV DNA PCR negative for high-risk HPV types by PCR at screening. Genotyping will be
 specified using a reverse line probe assay specific for the detection of high-risk HPV
 types such as HPV-16, HPV-18 and HPV-16/18-related phylogenetic types

 Exclusion Criteria:

 -  Pregnant or lactating female

 -  Female planning to become pregnant during the first eight months of the study (months
 0-8)

 -  Abnormal vaginal discharge at the time of entry (once these subjects have received
 therapy to eradicate any discharge they will be eligible to participate in study)

 -  Previous administration of any components of the investigational vaccine

 -  Chronic administration (defined as more than 14 days) of immuno-suppressants or other
 immune-modifying drugs within six months prior to the first vaccine dose.

 -  Administration of immunoglobulin and/or any blood products within the three months (90
 days) preceding the first dose of study vaccine or planned administration during the
 study period

 -  Planned administration / administration of a vaccine not foreseen by the study
 protocol within 30 days of the first dose of study vaccine. Administration of routine
 Meningococcal, Hepatitis A, Hepatitis B, Influenza, and Diphtheria/Tetanus vaccine up
 to 8 days before the first dose of study vaccine is allowed

 -  Use of any investigational or non-registered 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

 -  Receiving or expecting therapy for external or internal condylomata. Subjects with
 external condylomata not requiring therapy are eligible to participate in the study

 -  Genital herpes disease involving the cervix or characterized (on examination or by
 history) by extensive external lesions. Subjects with a history of recurrent genital
 herpes disease characterized by limited external lesions are eligible to participate
 in the study

 -  History of an abnormal cervical cytology (Pap smear) test (other than a single prior
 report of ASCUS with a subsequent normal report)

 -  Treatment for cervical disease by ablative therapy (cryotherapy or laser ablation) or
 excisional therapy (laser cone biopsy, loop excision, cold-knife conization)

 -  Any confirmed or suspected immunosuppressive or immunodeficient condition, including
 human immunodeficiency virus (HIV) infection

 -  A family history of congenital or hereditary immunodeficiency

 -  Major congenital defects or serious chronic illness

 -  History of any neurologic disorders or seizures, with the exception of a single
 febrile seizure during childhood

 -  Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal
 functional abnormality, as determined by physical examination or laboratory screening
 tests

 -  Acute disease at the time of enrolment.

 -  Oral temperature ≥99.5°F (≥37.5°C) / axillary temperature ≥99.5°F (37.5°C) / rectal
 temperature ≥100.4°F (≥38.0°C) / tympanic temperature on oral setting ≥99.5°F (37.5°C)
 / tympanic temperature on rectal setting ≥100.4°F (≥38.0°C)

 -  History of chronic alcohol consumption and/or intravenous drug abuse within the past 2
 years

 -  Known or suspected allergy to any vaccine component

 -  Hepatomegaly, right upper quadrant abdominal pain or tenderness