Clinical trial NCT00196937: Human Papilloma Virus (HPV) Vaccine Immunogenicity and Safety Trial in Young and Adult Women With GSK Biologicals' HPV-16/18
Official title: Phase 3, Open, Age-stratified Study to Assess Immunogenicity and Safety of GSK Biologicals' HPV-16/18 Vaccine Administered Intramuscularly According to 3-dose Schedule (0,1,6 Months) in Healthy Female Subjects Aged 15 - 55 Years and Long Term Follow-up
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Papillomavirus
Keywords: HPV Vaccine Safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-09-20
Enrollment: 667
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. Indeed, certain oncogenic types of HPV can infect the cervix (part of the uterus or womb). This infection may go 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. This study will evaluate the immunogenicity and safety of GSK Biologicals HPV-16/18 vaccine over 12 months, in women up to 55 years of age at study start. Approximately 660 study subjects will receive the HPV vaccine administered intramuscularly according to a 0-1-6 month schedule. The study will be extended to assess long-term safety and immunogenicity of the HPV-16/18 vaccine.


Eligibility criteria: Inclusion criteria for primary study:

* A woman who the investigator believes that she and/or her parents/legally acceptable representative can and will comply with the requirements of the protocol.
* A woman between, and including, 15 and 55 years of age at the time of the first vaccination.
* 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 and, in addition, the subject should sign and personally date a written informed assent).
* Free of obvious health problems.
* Subject must have a negative urine pregnancy test.
* Subject must be of non-childbearing potential or, if of childbearing potential, she must be abstinent or must be using adequate contraceptive precautions for 30 days prior to vaccination and must agree to continue such precautions for two months after completion of the vaccination series. Subjects who reach menarche during the study and therefore become of childbearing potential must agree to follow the same precautions

Inclusion criteria for extension studies

* A female who enrolled in the primary study and received three doses of vaccine.
* 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 and, in addition, the subject must sign and personally date a written informed assent).

Exclusion criteria for primary study:

* Pregnant or breastfeeding.
* A woman planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the study period, up to two months after the last vaccine dose.
* 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 (up to Month 12).
* Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose, or planned administration during the study period.
* Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after the first dose of study vaccine. Planned administration/administration of routine 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.
* Previous administration of components of the investigational vaccine
* Previous vaccination against HPV.
* Any medically diagnosed or suspected immunodeficient condition based on medical history and physical examination.
* History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccine.
* Hypersensitivity to latex.
* Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests.
* History of chronic condition(s) requiring treatment.
* Administration of immunoglobulins and/or any blood product within 3 months preceding the first dose of study vaccine or planned administration during the study period. Enrolment will be deferred until the subject is outside of specified window.
* Acute disease at the time of enrolment.

Exclusion criteria for extension studies

* 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 3 months prior to blood sampling.
* Administration of immunoglobulins and/or any blood products within the three months preceding blood sampling.

Primary outcomes:
measure: Number of Seroconverted Subjects for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies, in Women 15 to 25 Years of Age and Women 26 to 45 Years of Age
timeFrame: At Month 7
measure: Anti-HPV-16/18 Antibody Titers Assessed by ELISA Based on the ATP Cohort for Immunogenicity at Months 18, 24, 36 and 48
timeFrame: At Months 18, 24, 36 and 48
Secondary outcomes:
measure: Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies, in Women 46 - 55 Years of Age
timeFrame: At Month 7
measure: Anti-HPV-16/18 Antibody Titers Assessed by ELISA Based on the ATP Cohort for Immunogenicity at Pre-vaccination (PRE) and Months 2, 7 and 12
timeFrame: At PRE and Months 2, 7 and 12
measure: Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies at Month 2 and Month 12
timeFrame: At Month 2 and Month 12
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 7-day period (from the day of vaccination up to 6 subsequent days) following vaccination after each dose and across doses
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 7-day period (from the day of vaccination up to 6 subsequent days) following vaccination after each dose and across doses
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
timeFrame: During the 30-day (from the day of vaccination up to 29 subsequent days) post-vaccination period
measure: Number of Subjects Reporting Serious Adverse Events (SAE)
timeFrame: During the entire study period (from Day 0 up to Month 48)
measure: Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs)
timeFrame: During the entire study period (from Day 0 up to Month 48)
measure: Number of Subjects Reporting Medically Significant Conditions
timeFrame: During the entire study period (from Day 0 up to Month 48)
measure: Anti-HPV-16/18 Antibody Titers Assessed by ELISA in a Subset of Subjects in Cervical Secretions (CVS) Samples
timeFrame: At Months 18 and 24
measure: Number of Subjects Seropositive for Total Immunoglobulin-G (IgG) in Blood (Serum) and in Cervical Samples (Secretion) in a Subset of Subjects
timeFrame: At Months 18 and 24
measure: Number of Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies
timeFrame: During the entire study period (from Day 0 up to Month 48)
Other outcomes:
Locations:
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Wuerzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Descamps D, Hardt K, Spiessens B, Izurieta P, Verstraeten T, Breuer T, Dubin G. Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials. Hum Vaccin. 2009 May;5(5):332-40. doi: 10.4161/hv.5.5.7211. Epub 2009 May 20.
citation: Schwarz TF, Spaczynski M, Schneider A, Wysocki J, Galaj A, Perona P, Poncelet S, Zahaf T, Hardt K, Descamps D, Dubin G; HPV Study Group for Adult Women. Immunogenicity and tolerability of an HPV-16/18 AS04-adjuvanted prophylactic cervical cancer vaccine in women aged 15-55 years. Vaccine. 2009 Jan 22;27(4):581-7. doi: 10.1016/j.vaccine.2008.10.088. Epub 2008 Nov 18.
citation: Schwarz TF, Spaczynski M, Schneider A, Wysocki J, Galaj A, Schulze K, Poncelet SM, Catteau G, Thomas F, Descamps D. Persistence of immune response to HPV-16/18 AS04-adjuvanted cervical cancer vaccine in women aged 15-55 years. Hum Vaccin. 2011 Sep;7(9):958-65. doi: 10.4161/hv.7.9.15999. Epub 2011 Sep 1.
citation: Schwarz TF, Kocken M, Petaja T, Einstein MH, Spaczynski M, Louwers JA, Pedersen C, Levin M, Zahaf T, Poncelet S, Hardt K, Descamps D, Dubin G. Correlation between levels of human papillomavirus (HPV)-16 and 18 antibodies in serum and cervicovaginal secretions in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine. Hum Vaccin. 2010 Dec;6(12):1054-61. doi: 10.4161/hv.6.12.13399. Epub 2010 Dec 1.
citation: Schwarz T, Spaczynski M, Kaufmann A, Wysocki J, Galaj A, Schulze K, Suryakiran P, Thomas F, Descamps D. Persistence of immune responses to the HPV-16/18 AS04-adjuvanted vaccine in women aged 15-55 years and first-time modelling of antibody responses in mature women: results from an open-label 6-year follow-up study. BJOG. 2015 Jan;122(1):107-18. doi: 10.1111/1471-0528.13070. Epub 2014 Sep 11.
citation: Boxus M, Lockman L, Fochesato M, Lorin C, Thomas F, Giannini SL. Antibody avidity measurements in recipients of Cervarix vaccine following a two-dose schedule or a three-dose schedule. Vaccine. 2014 May 30;32(26):3232-6. doi: 10.1016/j.vaccine.2014.04.005. Epub 2014 Apr 13.