Human Papilloma Virus (HPV) Vaccine Efficacy Trial Against Cervical Pre-cancer in Young Adults With GSK Biologicals HPV-16/18 - Full Text View

Sponsor:	GlaxoSmithKline
Information provided by:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00122681

Purpose

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 efficacy of GSK Biologicals HPV 16/18 VLP/AS04 vaccine to prevent infection associated cervical pre-cancer and vaccine with HPV 16 or 18 and the vaccine safety, over 48 months, in young adolescents and women of 15/25 years of age at study start. Approximately 18.000 study subjects will either receive the HPV vaccine or a control vaccine (hepatitis A 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.

Condition	Intervention	Phase
Human Papillomavirus (HPV) Infection Cervical Neoplasia	Biological: GSK Biologicals' Human Papillomavirus vaccine Biological: Investigational Hepatitis A vaccine	Phase III

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Safety/Efficacy Study
Official Title:	Efficacy of GSK Bio HPV Vaccine (580299) vs Hepatitis A Vaccine as Control in Prevention of Persistent HPV-16/18 Cervical Infection & Cervical Neoplasia, Administered IM According to 0,1,6 Month Schedule in Healthy Females (15-25 y)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Hepatitis Hepatitis A

Drug Information available for: Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Histopathologically confirmed CIN2+ associated with HPV-16 or HPV-18 cervical infection detected within the lesional component of the cervical tissue specimen, overall and stratified according to initial (M0) HPV-16 or 18 serostatus. [ Time Frame: At the time of analysis ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Occurrence, intensity, relationship to vaccination & resulting school or work absenteeism of any sol local or gen symptoms & stratified by initial(M0) HPV-16/18 DNA status & acc to HPV-16 or 18 serostatus in a subset of subjects from selected study sites [ Time Frame: Within 7 days after each vaccination dose ] [ Designated as safety issue: No ]
Occurrence, intensity, relationship to vaccination & resulting school or work absenteeism of any unsolicited symptoms & stratified by initial (M0) HPV-16/18 DNA status & according to HPV-16/18 serostatus in a subset of subjects from selected study sites [ Time Frame: Within 30 days after any vaccination ] [ Designated as safety issue: No ]
Occurrence of SAEs stratified by initial (Month 0) HPV-16/18 DNA status and according to HPV-16 or 18 serostatus in all subjects [ Time Frame: Throughout the entire study period (Month 0 to Month 48) ] [ Designated as safety issue: No ]
Occurrence of new onset chronic disease stratified by initial (Month 0) HPV-16/18 DNA status and according to HPV 16 or 18 serostatus in all subjects [ Time Frame: Throughout the entire study (Month 0 to 48) ] [ Designated as safety issue: No ]
Occurrence of medically significant conditions stratified by initial (Month 0) HPV-16/18 DNA status and according to HPV-16 or 18 serostatus [ Time Frame: Throughout entire study period (Month 0 to Month 48) ] [ Designated as safety issue: No ]
Outcome of all pregnancies, overall and stratified by initial (Month 0) HPV-16/18 DNA status and according to HPV-16 or -18 serostatus [ Time Frame: Throughout the entire study period (Month 0 to Month 48) ] [ Designated as safety issue: No ]
Persistent infection (12M definition) with HPV-16 or HPV-18, overall and stratified according to initial (Month 0) HPV-16 or HPV-18 serostatus. [ Time Frame: At the time of analysis ] [ Designated as safety issue: No ]
Persistent infection (6M definition) with HPV-16 or HPV-18, overall and stratified according to initial (Month 0) HPV-16 or HPV-18 serostatus. [ Time Frame: At the time of analysis ]
Persistent infection (6M definition) with oncogenic HPV types. [ Time Frame: At the time of analysis ] [ Designated as safety issue: No ]
Histopathologically confirmed CIN2+ associated with oncogenic HPV types detected within the lesional component of the cervical tissue specimen. [ Time Frame: At the time of analysis ] [ Designated as safety issue: No ]
Histopathologically confirmed CIN1+ associated with HPV-16 or HPV-18 detected within the lesional component of the cervical tissue specimen, overall and stratified according to initial (Month 0) HPV-16 or 18 serostatus. [ Time Frame: At the time of analysis ] [ Designated as safety issue: No ]
Histopathologically confirmed CIN1+ associated with oncogenic HPV types detected within the lesional component of the cervical tissue specimen. [ Time Frame: At the time of analysis ] [ Designated as safety issue: No ]
HPV-16 and HPV-18 ELISA titers and seroconversion (in the immunogenicity subset according to initial (Month 0) HPV-16 or HPV-18 serostatus [ Time Frame: At the time of analysis ] [ Designated as safety issue: No ]
HPV-16 and HPV-18 seroconversion and titers (ELISA & V5/J4 monoclonal inhibition test) in vaccine recipients with breakthrough HPV-16 and/or HPV-18 infections & associated neoplasias compared with selected non-cases [ Time Frame: At the time of analysis ] [ Designated as safety issue: No ]

Estimated Enrollment:	18673
Study Start Date:	May 2004
Estimated Study Completion Date:	September 2009
Estimated Primary Completion Date:	September 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group B: Active Comparator	Biological: Investigational Hepatitis A vaccine Intramuscular injection, 3 doses
Group A: Experimental	Biological: GSK Biologicals' Human Papillomavirus vaccine Intramuscular injection, 3 doses

Detailed Description:

NOTE: Some 178 centers participate in this study. Given that the recruitment is completed, the researchers have listed one center per country in this website. If required, further details of centers available on request.

Eligibility

Ages Eligible for Study:	15 Years to 25 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

A woman whom the investigator believes that she and/or her parents/legally acceptable representative can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits).
A woman between, and including, 15 and 25 years of age at the time of the first vaccination.
Written informed consent must be obtained from the subject prior to enrollment (for subjects below the legal age of consent, written informed consent must be obtained from a parent or legal guardian of the subject and, in addition, the subject should sign and personally date a written informed assent).
Subject must be free of obvious health problems as established by medical history and clinical examination before entering into the study.
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 the first vaccination and must agree to continue such precautions for two months after completion of the vaccination series.
Has had no more than 6 lifetime sexual partners prior to enrollment. This criterion may not be applicable in subjects less than 18 years of age, according to local regulatory/ethical requirements.
Subject must have intact cervix.

Exclusion Criteria:

Pregnant or breastfeeding. Women must be at least 3 months post-pregnancy and not breastfeeding to enter the study.
A woman planning to become pregnant or planning to discontinue contraceptive precautions during approximately the first nine months of the study (Months 0-8).
Previous administration of components of the investigational vaccine.
Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after (i.e. days 0-29) each dose of vaccine. Administration of some routine vaccines up to 8 days before each dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window.
Previous vaccination against human papillomavirus (HPV).
History of vaccination against Hepatitis A or a known clinical history of Hepatitis A disease.
History of having had colposcopy or has planned a colposcopy to evaluate an abnormal cervical cytology (Pap smear) test.
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 vaccines.
Hypersensitivity to latex.
Known acute or chronic, clinically significant pulmonary, cardiovascular, neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests.
History of chronic condition(s) requiring treatment.
Received immunoglobulins and/or blood product within 90 days preceding enrollment. Enrollment will be deferred until the subject is outside of specified window.
Acute disease at the time of enrolment.
Heavy bleeding (menstruation or other) or heavy vaginal discharge in which a pelvic exam cannot be performed. Enrollment will be deferred until condition is resolved according to investigator's medical judgement.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00122681

Show 132 Study Locations

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Paavonen J, Naud P, Salmerón J, Wheeler CM, Chow SN, Apter D, Kitchener H, Castellsague X, Teixeira JC, Skinner SR, Hedrick J, Jaisamrarn U, Limson G, Garland S, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, Jenkins D, Hardt K, Zahaf T, Descamps D, Struyf F, Lehtinen M, Dubin G; HPV PATRICIA Study Group; Greenacre M. Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet. 2009 Jul 25;374(9686):301-14. Epub 2009 Jul 6.

Paavonen J, Jenkins D, Bosch FX, Naud P, Salmeron J, Wheeler CM, Chow SN, Apter DL, Kitchener HC, Castellsague X, de Carvalho NS, Skinner SR, Harper DM, Hedrick JA, Jaisamrarn U, Limson GA, Dionne M, Quint W, Spiessens B, Peeters P, Struyf F, Wieting SL, Lehtinen MO, Dubin G; HPV PATRICIA study group. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial. Lancet. 2007 Jun 30;369(9580):2161-70.

Responsible Party:	GSK ( Study Director )
Study ID Numbers:	580299/008
Study First Received:	July 20, 2005
Last Updated:	September 17, 2009
ClinicalTrials.gov Identifier:	NCT00122681 History of Changes
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Communicable Diseases
Neoplasms
Infection

ClinicalTrials.gov processed this record on November 27, 2009