Evaluation of Safety and Immunogenicity of Co-administering Human Papillomavirus Vaccine With Another Vaccine in Healthy Female Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00578227
First received: December 20, 2007
Last updated: February 7, 2013
Last verified: February 2013
  Purpose

Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. Vaccination of pre-teens and adolescents, ideally before sexual debut and thus before exposure to oncogenic HPV, is a rational strategy for prevention of cervical cancer, and so HPV vaccination could complement the existing pre-adolescent/adolescent vaccination programs. Therefore, this Phase IIIb study is designed to evaluate the safety and immunogenicity of co-administering a commercially available vaccine with GSK Biologicals' HPV-16/18 L1 AS04 (Cervarix ®) vaccine as compared to the administration of either vaccine alone. This Protocol Posting has been updated in order to comply with the FDA AA, Sept 2007.


Condition Intervention Phase
Human Papillomavirus (HPV) Infection
Papillomavirus Vaccines
Biological: Cervarix™
Biological: Twinrix ™ Paediatric
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Immunogenicity and Safety Study of GSK Biologicals' HPV Vaccine (GSK-580299) Co-administered With a Commercially Available Vaccine in Healthy Female Adolescents

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects Seroconverted for Anti-hepatitis A (Anti-HAV) Antibodies [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]
    Seroconversion is defined as the appearance of anti-HAV antibodies [i.e., antibody titer greater than or equal to 15 milli-international units/milliliter (mIU/mL)] in the sera of subjects seronegative (antibody titer below 15 mIU/mL) before vaccination.

  • Anti-Heptatis A (HAV) Antibody Titers. [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]
    Titers are given as Geometric Mean Titers (GMTs) expressed as mIU/mL.

  • Number of Subjects Seroprotected for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]
    A subject seroprotected against HBs is a subject with antibody titers greater than or equal to 10 mIU/mL.

  • Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]
    Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values = 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.

  • Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]
    Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).


Secondary Outcome Measures:
  • Anti-HBs Antibody Titers [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]
    Titers are given as Geometric Mean Titers (GMTs)expressed as mIU/mL.

  • Number of Subjects Seroconverted for Anti-HBs Antibodies [ Time Frame: At month 7 ] [ Designated as safety issue: No ]
    Seroconversion is defined as the appearance of anti-HBs antibodies (i.e., antibody titer greater than or equal to 3.3 mIU/mL) in the sera of subjects seronegative (with antibody titers below 3.3 mIU/mL) before vaccination.

  • Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies in Vaccine Recipients Aged 9 Years [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]
    Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values = 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.

  • Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers in Vaccine Recipients Aged 9 Years [ Time Frame: At Month 7 ] [ Designated as safety issue: No ]
    Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).

  • Number of Subjects Seroconverted for Anti-HAV Antibodies [ Time Frame: One month after the second dose of vaccine ] [ Designated as safety issue: No ]
    Seroconversion is defined as the appearance of anti-HAV antibodies (i.e., antibody titer greater than or equal to 15 mIU/mL) in the sera of subjects seronegative (antibody titer below 15 mIU/mL) before vaccination.

  • Anti-HAV Antibody Titers [ Time Frame: One month after the second dose of vaccine ] [ Designated as safety issue: No ]
    Titers are given as geometric mean titers (GMTs) expressed as mIU/mL.

  • Number of Subjects Seroconverted and Number of Subjects Seroprotected for Anti-HBs Antibodies [ Time Frame: One month after the second dose of vaccine ] [ Designated as safety issue: No ]

    Seroconversion is defined as the appearance of anti-HBs antibodies (i.e., antibody titer greater than or equal to 3.3 mIU/mL) in the sera of subjects seronegative (with antibody titers below 3.3 mIU/mL) before vaccination.

    A seroprotected subject against HBs is a subject with antibody titers greater than or equal to 10 mIU/mL.


  • Anti-HBs Antibody Titers [ Time Frame: One month after the second dose of vaccine ] [ Designated as safety issue: No ]
    Titers are given as geometric mean titers (GMTs) expressed as mIU/mL.

  • Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies [ Time Frame: One month after the second dose of vaccine ] [ Designated as safety issue: No ]
    Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values assessed include 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.

  • Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibody Titers [ Time Frame: One month after the second dose of vaccine ] [ Designated as safety issue: No ]
    Titers are given as Geometric Mean Titers (GMTs) expressed as EL.U/mL.

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

  • Number of Subjects Reporting Solicited General Symptoms [ Time Frame: During the 7-day period following vaccination ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed include arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, temperature [axillary route, greater than or equal to 37.5 degree Celsius (°C)] and urticaria.

  • Number of Subjects Reporting Medically Significant Conditions [ Time Frame: Throughout the active phase of the study (up to Month 7) ] [ Designated as safety issue: No ]
    Medically significant conditions include adverse events (AEs) prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.

  • Number of Subjects Reporting Medically Significant Conditions [ Time Frame: Throughout the safety follow-up (from Month 7 up to Month 12) ] [ Designated as safety issue: No ]
    Medically significant conditions include adverse events (AEs) prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.

  • Number of Subjects Reporting Unsolicited Adverse Events [ Time Frame: During the 30-day period following any vaccination ] [ Designated as safety issue: No ]
    Unsolicited adverse events include any adverse event reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

  • Number of Subjects Reporting Serious Adverse Events (SAE) [ Time Frame: Throughout the study (up to Month 12) ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.


Enrollment: 814
Study Start Date: December 2007
Study Completion Date: April 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cervarix™ & Twinrix™ Group
Subjects received 3 doses of Human Papilloma Virus (HPV) vaccine co-administered with combined Hepatitis A & Hepatitis B (HAB) vaccine (Months 0, 1 & 6).
Biological: Cervarix™
Three doses of vaccine administered intramuscularly with the second and third dose given one month and six months after the first dose
Other Names:
  • HPV vaccine
  • GSK Biologicals' HPV-16/18 L1 AS04
Biological: Twinrix ™ Paediatric
Three doses of vaccine administered intramuscularly with the second and third dose given one month and six months after the first dose
Experimental: Cervarix™ Group
Subjects received 3 doses of HPV vaccine (Months 0, 1 & 6).
Biological: Cervarix™
Three doses of vaccine administered intramuscularly with the second and third dose given one month and six months after the first dose
Other Names:
  • HPV vaccine
  • GSK Biologicals' HPV-16/18 L1 AS04
Active Comparator: Twinrix™ Group
Subjects received 3 doses of HAB vaccine (Months 0, 1 & 6).
Biological: Twinrix ™ Paediatric
Three doses of vaccine administered intramuscularly with the second and third dose given one month and six months after the first dose

  Eligibility

Ages Eligible for Study:   9 Years to 15 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes that they and/or their legally acceptable representatives (LARs) can and will comply with the requirements of the protocol should be enrolled in the study.
  • A female between, and including, 9 and 15 years of age (has not attained her 16th birthday) 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 the subject's LAR, and written informed assent must be obtained from the subject.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • Subjects must not be pregnant.
  • Subjects must be of non-childbearing potential, or if the subject is of childbearing potential, she must be abstinent or use adequate contraception for 30 days prior to vaccination and must agree to continue such precautions for two months after completion of the vaccination series.

Exclusion Criteria:

  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 12).
  • Concurrently participating in another clinical study, at any time during the study period (up to the Month 12 telephone contact), 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 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 each dose of vaccine(s). Administration of routine vaccines may be allowed up to 8 days before the first dose
  • A subject planning to become pregnant, likely to become pregnant or planning to discontinue contraceptive precautions during the study period and up to two months after the last vaccine dose.
  • Pregnant or breastfeeding women.
  • Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period.
  • Previous administration of components of the investigational vaccine.
  • Previous vaccination against hepatitis A or B planned administration of any hepatitis A or B vaccine other than that foreseen by the study protocol during the study period.
  • History of hepatitis A or B infection.
  • Known exposure to hepatitis A or B within the previous 6 weeks.
  • Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests.
  • Cancer or autoimmune disease under treatment.
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccines
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination
  • Acute disease at the time of enrolment.
  • Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00578227

Locations
Canada, British Columbia
GSK Investigational Site
Surrey, British Columbia, Canada, V3R 8P8
Canada, Ontario
GSK Investigational Site
Brampton, Ontario, Canada, L6T 3T1
GSK Investigational Site
Newmarket, Ontario, Canada, L3Y 5G8
GSK Investigational Site
Sarnia, Ontario, Canada, N7T 4X3
GSK Investigational Site
Sudbury, Ontario, Canada, P3E 1H5
Denmark
GSK Investigational Site
Hoersholm, Denmark, 2970
GSK Investigational Site
Odense C, Denmark, 5000
Hungary
GSK Investigational Site
Bordány, Hungary, 6795
GSK Investigational Site
Budapest, Hungary, 1089
GSK Investigational Site
Budapest, Hungary, 1033
GSK Investigational Site
Budapest, Hungary, 1032
GSK Investigational Site
Budapest, Hungary, 1039
GSK Investigational Site
Győr, Hungary, 9024
GSK Investigational Site
Hódmezővásárhely, Hungary, 6800
GSK Investigational Site
Szeged, Hungary, 6723
GSK Investigational Site
Szombathely, Hungary, 9700
Sweden
GSK Investigational Site
Karlskrona, Sweden, SE-371 41
GSK Investigational Site
Linköping, Sweden, SE-581 85
GSK Investigational Site
Lycksele, Sweden, SE-921 82
GSK Investigational Site
Umeå, Sweden, SE-901 85
GSK Investigational Site
Örebro, Sweden, SE-702 11
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 ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00578227     History of Changes
Other Study ID Numbers: 110886
Study First Received: December 20, 2007
Results First Received: November 27, 2009
Last Updated: February 7, 2013
Health Authority: Hungary: Országos Gyógyszerészeti Intézet
Canada: Health Canada
Denmark: Danish Medicines Agency
Sweden: Medical Products Agency

Keywords provided by GlaxoSmithKline:
Human papillomavirus infection,
cervical cancer
HPV vaccine,

ClinicalTrials.gov processed this record on April 21, 2014