Clinical trial NCT00689741: Efficacy Study of HPV-16/18 Vaccine (GSK 580299) to Prevent HPV-16 and/or -18 Cervical Infection in Young Healthy Women
Official title: A Double-blind, Placebo-controlled, Randomised Study of the Efficacy of an HPV-16/18 VLP Vaccine in the Prevention of HPV-16 and/or HPV-18 Cervical Infection in Healthy Adolescent and Young Adult Women in North America and Brazil.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infections, Papillomavirus
Keywords: HPV
vaccine
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-06-04
Enrollment: 1113
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Cervical infection with HPV-16 and/or HPV-18
timeFrame: Throughout the study
Secondary outcomes:
measure: Persistent cervical infection with HPV-16 and/or HPV-18
timeFrame: Throughout the study
measure: Cytologically confirmed or histopathologically confirmed LSIL, HSIL, squamous cell cancer, or adenocarcinoma concurrently associated with HPV-16 and/or HPV-18 cervical infection
timeFrame: Throughout the study
measure: Determination of viral load for HPV-16 and HPV-18 (by PCR) for both self-obtained and Pap smear cervical samples
timeFrame: Throughout the study
measure: Cervical infection with HPV-16, HPV-18 and/or HPV-16/18-related phylogenetic types
timeFrame: Throughout the study
measure: Persistent cervical infection with HPV-16, HPV-18 and/or HPV-16/18-related phylogenetic types
timeFrame: Throughout the study
measure: Cytologically confirmed or histopathologically confirmed LSIL, HSIL, squamous cell cancer, adenocarcinoma concurrently associated with cervical infection with HPV-16; HPV-18 and/or HPV-16/18-related phylogenetic types.
timeFrame: Throughout the study
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
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citation: David MP et al. Long-term persistence of detectable anti-HPV-16 and anti-HPV-18 antibodies induced by CervarixTM: modelling of sustained antibody responses. Abstract presented at the 26th Annual Meeting of the ESPID. Graz, Austria, 13-17 May 2008.
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