Human Papilloma Virus (HPV) Vaccine Immunogenicity and Safety Trial in Young and Adult Women With GSK Biologicals' HPV-16/18

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00196937
First received: September 13, 2005
Last updated: June 12, 2014
Last verified: January 2012
  Purpose

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.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.


Condition Intervention Phase
Infections, Papillomavirus
Biological: Cervarix™
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects Seroconverted 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 [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]

    Seroconversion is defined as the appearance of anti-HPV-16 and/or anti- HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the sera of subjects seronegative before vaccination.

    Cut-off values were 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.

    Seroconversion at Month 7 was a secondary outcome measure as per protocol for Cervarix (46-55 Years) Group.


  • Titer of Anti-HPV-16 and Anti-HPV-18 Antibodies [ Time Frame: Before vaccination (PRE) and at Months 2, 7, 12, 18, 24, 36 and 48 ] [ Designated as safety issue: No ]

    Titer given as geometric mean titer (GMT).

    Primary outcome measure assessed at Month 18, 24, 36, and 48.



Secondary Outcome Measures:
  • Titer of Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervical Samples [ Time Frame: At Months 18 and 24 ] [ Designated as safety issue: No ]
    Titer given as GMT.

  • Number of Subjects Seropositive for Total Immunoglobulin-G (IgG) in Blood (Serum) and in Cervical Samples (Secretion) [ Time Frame: At Months 18 and 24 ] [ Designated as safety issue: No ]
    Seropositivity is defined as total IgG above or equal to 0 microgram per milliliter (µg/mL).

  • Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies, in Women 46 - 55 Years of Age [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]

    Seroconversion is defined as the appearance of anti-HPV-16 and/or anti- HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the sera of subjects seronegative before vaccination.

    Cut-off values were 8 EL.U/mL for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.

    Seroconversion results at Month 7 for the other 2 groups are already presented in the primary outcome measure #1.


  • Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies After 2 Vaccine Doses and 6 Months Following the Complete Vaccination Course [ Time Frame: At Month 2 and Month 12 ] [ Designated as safety issue: No ]

    Seroconversion is defined as the appearance of anti-HPV-16 and/or anti- HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the sera of subjects seronegative before vaccination.

    Cut-off values were 8 EL.U/mL for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.

    Seroconversion results at Month 7 (1 month after the complete vaccination course) are already presented above as primary outcome measure #1 for Cervarix (15-25 Years) Group and Cervarix (26-45 Years) Group and as secondary outcome measure #6 for Cervarix (46-55 Years) Group.


  • Number of Subjects Reporting Solicited Local Symptoms [ Time Frame: During the 7-day (Days 0-6) period following each vaccination ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed include pain, redness and swelling at the injection site.

  • Number of Subjects Reporting Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) period following each vaccination ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed include arthralgia, fatigue, fever, gastrointestinal symptoms, headache, myalgia, rash, and urticaria.

  • Number of Subjects Reporting Unsolicited Adverse Events (AE) [ Time Frame: During the 30-day (Days 0-29) period following each vaccination ] [ Designated as safety issue: No ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  • Number of Subjects Reporting Serious Adverse Events (SAE) [ Time Frame: During the entire study period (up to Month 48) ] [ Designated as safety issue: No ]
    An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.

  • Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Medically Significant Conditions (MSAEs) [ Time Frame: During the entire study period (up to Month 48) ] [ Designated as safety issue: No ]
    NOCDs assessed include e.g. autoimmune disorders, asthma, type I diabetes. MSAEs assessed include AEs prompting emergency room visits and physician office visits not related to common illnesses.


Enrollment: 667
Study Start Date: October 2004
Study Completion Date: February 2009
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cervarix (15-25 Years) Group
Women aged 15 to 25 years received 3 doses of Cervarix™ (human papillomavirus [HPV] vaccine) administered according to a 0, 1, 6-month schedule.
Biological: Cervarix™
Three doses of vaccine administered intramuscularly according to a 0, 1, 6 months
Other Name: GSK Biologicals' human papillomavirus (HPV)-16/18 L1/AS04
Experimental: Cervarix (26-45 Years) Group
Women aged 26 to 45 years received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Biological: Cervarix™
Three doses of vaccine administered intramuscularly according to a 0, 1, 6 months
Other Name: GSK Biologicals' human papillomavirus (HPV)-16/18 L1/AS04
Experimental: Cervarix (46-55 Years) Group
Women aged 46 to 55 years received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Biological: Cervarix™
Three doses of vaccine administered intramuscularly according to a 0, 1, 6 months
Other Name: GSK Biologicals' human papillomavirus (HPV)-16/18 L1/AS04

  Eligibility

Ages Eligible for Study:   15 Years to 55 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00196937

Locations
Germany
GSK Investigational Site
Muenchen, Bayern, Germany, 80799
GSK Investigational Site
Wuerzburg, Bayern, Germany, 97070
GSK Investigational Site
Berlin, Germany, 12200
Poland
GSK Investigational Site
Bydgoszcz, Poland, 85-021
GSK Investigational Site
Poznan, Poland, 60-533
GSK Investigational Site
Poznan, Poland, 61-709
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00196937     History of Changes
Obsolete Identifiers: NCT00332358, NCT00332475, NCT00332501, NCT00332527
Other Study ID Numbers: 103514, 105879, 105880, 105881, 105882
Study First Received: September 13, 2005
Results First Received: November 12, 2009
Last Updated: June 12, 2014
Health Authority: Poland: URZ.D REJESTRACJI PRODUKTÓW LECZNICZYCH, WYROBÓW MEDYCZNYCH I PRODUKTÓW BIOBÓJCZYCH,CEBK
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by GlaxoSmithKline:
HPV Vaccine Safety

ClinicalTrials.gov processed this record on July 23, 2014