Evaluation of Safety and Immunogenicity of Co-administering HPV Vaccine With Other Vaccines in Healthy Female Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00369824
First received: August 28, 2006
Last updated: November 21, 2012
Last verified: November 2012
  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/adolescents platform. Therefore, this Phase 3b study is designed to evaluate the safety and immunogenicity of co-administering Boostrix and/or Menactra with GSK Biologicals' HPV vaccine (580299) as compared to the administration of any of the vaccines alone.

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


Condition Intervention Phase
Human Papillomavirus Type-16/-18 Infection
Papillomavirus Vaccines
Cervical Neoplasia
Biological: Different formulations of GSK Biologicals' HPV vaccine (580299)
Biological: Menactra TM
Biological: Boostrix TM
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: A Randomized, Open Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline Biologicals' HPV Vaccine Co-administered Intramuscularly With Boostrix® and/or Menactra™ in Healthy Female Subjects Aged 11-18 Years

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Anti-diphtheria Toxoid (Anti-D) and Anti-tetanus Toxoid (Anti-T) Antibody Concentrations Above 1.0 International Unit Per Milliliter (IU/mL) [ Time Frame: Before and one month after vaccination with Boostrix ] [ Designated as safety issue: No ]
    Anti-D and anti-T antibodies cut-off values assessed include 1.0 international unit per milliliter (IU/mL)

  • Concentration of Anti-pertussis Toxoid (Anti-PT), Anti-pertactin (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) Antibodies [ Time Frame: Before and one month after vaccination with Boostrix ] [ Designated as safety issue: No ]
    Concentrations given as Geometric Means Concentrations (GMCs)

  • Titer of Meningococcal Serogroup A (Anti-A), Meningococcal Serogroup C (Anti-C), Meningococcal Serogroup Y (Anti-Y) and Meningococcal Serogroup W-135 (Anti-W135) Antibodies [ Time Frame: Before and one month after vaccination with Menactra ] [ Designated as safety issue: No ]
    Titers given as Geometric Mean Titers (GMTs)


Secondary Outcome Measures:
  • Number of Subjects With Anti-human Papilloma Virus 16 (Anti-HPV16) and Anti-human Papilloma Virus 18 (Anti-HPV18) Antibody Concentrations Above Pre-defined Cut-off Values [ Time Frame: Before vaccination (PRE), one month post Dose 2 (Mth2) and one and six months post Dose 3 (Mth 7 and Mth 12) ] [ Designated as safety issue: No ]
    Cut-off values assessed include 8 enzyme-linked immunosorbent assay units Per Milliliter (EL.U/mL) for anti-HPV16 antibodies and 7 EL.U/mL for anti-HPV18 antibodies.

  • Number of Subjects With Anti-diphtheria Toxoid (Anti-D) and Anti-tetanus Toxoid (Anti-T) Antibody Concentrations Above 0.1 International Unit Per Milliliter (IU/mL) [ Time Frame: Before and one month after vaccination with Boostrix ] [ Designated as safety issue: No ]
    Anti-D and anti-T antibodies cut-off values assessed include 0.1 international unit per milliliter (IU/mL)

  • Concentration of Anti-D and Anti-T Antibodies [ Time Frame: Before and one month after vaccination with Boostrix ] [ Designated as safety issue: No ]
    Concentrations given as Geometric Mean Concentrations (GMCs)

  • Number of Subjects With Booster Response for Anti-D and Anti-T [ Time Frame: One month after vaccination with Boostrix ] [ Designated as safety issue: No ]

    Booster responses for anti-D and anti-T defined as:

    • For initially seronegative subjects (pre-vaccination titer below cut-off: < 0.1 IU/mL): antibody titer at least 4 times the cut-off (post-vaccination titer ≥ 0.4 IU/mL)
    • For initially seropositive subjects (pre-vaccination titer above 0.1 IU/mL): an increase in antibody titer of at least 4 times the pre-vaccination titer

  • Number of Subjects With Booster Response for Anti-PT, Anti-FHA and Anti-PRN [ Time Frame: One month after vaccination with Boostrix ] [ Designated as safety issue: No ]

    Booster responses defined as:

    • For initially seronegative subjects (pre-vaccination titer below cut-off: < 5 EL.U/mL): antibody titers at least 4 times the cut-off,
    • For initially seropositive subjects with pre-vaccination titer above 5 EL.U/mL and < 20 EL.U/mL: an increase in antibody titers of at least 4 times the pre-vaccination titer,
    • For initially seropositive subjects with pre-vaccination titer ≥ 20 EL.U/mL: an increase in antibody titers of at least two times the pre-vaccination titer

  • Number of Subjects With Anti-A, Anti-C, Anti-Y and Anti-W135 Vaccine Response [ Time Frame: One month after vaccination with Menactra ] [ Designated as safety issue: No ]

    Vaccine responses for anti-A, C, Y and W-135 defined as:

    • For initially seronegative subjects (pre-vaccination titer below cut-off of 8): antibody titers at least 4 times the cut-off (post vaccination titer ≥ 32)
    • For initially seropositive subjects (pre-vaccination titer above 8): antibody titers at least 4 times the pre-vaccination antibody titer

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

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

  • Number of Subjects Reporting Unsolicited Adverse Events (AEs) [ Time Frame: During the 30-day period following each vaccination ] [ Designated as safety issue: No ]
    Unsolicited adverse event = Any adverse event (AE) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.

  • Number of Subjects Reporting Serious Adverse Events [ Time Frame: During the active phase of the study (up to Month 7 or Month 8) and throughout the entire study (up to Month 12 or Month 13) ] [ Designated as safety issue: No ]
    Serious adverse events assessed include medical occurrences that results in death, is 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.

  • Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) [ Time Frame: During the active phase of the study (up to Month 7 or Month 8) and throughout the entire study period (up to Month 12 or Month 13) ] [ Designated as safety issue: No ]
    NOCDs assessed include e.g. autoimmune disorders, asthma, type I diabetes

  • Number of Subjects Reporting Medically Significant Adverse Events (AEs) [ Time Frame: During the active phase (up to Month 7 or Month 8) and throughout the entire study (up to Month 12 or Month 13) ] [ Designated as safety issue: No ]
    Medically significant AEs assessed include AEs prompting emergency room or physician visits that are not related to common diseases or SAEs that are not related to common diseases.


Enrollment: 1330
Study Start Date: September 2006
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cervarix + Boostrix/Menactra Group
Subjects received Cervarix and Boostrix at Month 0, Menactra and Cervarix at Month 1 and Cervarix alone at Month 6.
Biological: Different formulations of GSK Biologicals' HPV vaccine (580299)
Three doses of vaccine administered intramuscularly, with the second and third dose given one month and six months after the first dose respectively
Biological: Menactra TM
One dose of vaccine administered intramuscularly
Biological: Boostrix TM
One dose of vaccine administered intramuscularly
Experimental: Cervarix + Menactra/Boostrix Group
Subjects received Menactra and Cervarix at Month 0, Boostrix and Cervarix at Month 1 and Cervarix alone at Month 6.
Biological: Different formulations of GSK Biologicals' HPV vaccine (580299)
Three doses of vaccine administered intramuscularly, with the second and third dose given one month and six months after the first dose respectively
Biological: Menactra TM
One dose of vaccine administered intramuscularly
Biological: Boostrix TM
One dose of vaccine administered intramuscularly
Experimental: Cervarix + Boostrix + Menactra Group
Subjects received Boostrix, Menactra and Cervarix at Month 0 and Cervarix alone at Months 1 and 6.
Biological: Different formulations of GSK Biologicals' HPV vaccine (580299)
Three doses of vaccine administered intramuscularly, with the second and third dose given one month and six months after the first dose respectively
Biological: Menactra TM
One dose of vaccine administered intramuscularly
Biological: Boostrix TM
One dose of vaccine administered intramuscularly
Experimental: Boostrix/Cervarix Group
Subjects received Boostrix at Month 0 and Cervarix at Months 1, 2 and 7.
Biological: Different formulations of GSK Biologicals' HPV vaccine (580299)
Three doses of vaccine administered intramuscularly, with the second and third dose given one month and six months after the first dose respectively
Biological: Menactra TM
One dose of vaccine administered intramuscularly
Biological: Boostrix TM
One dose of vaccine administered intramuscularly
Experimental: Menactra/Cervarix Group
Subjects received Menactra at Month 0 and Cervarix at Months 1, 2 and 7.
Biological: Different formulations of GSK Biologicals' HPV vaccine (580299)
Three doses of vaccine administered intramuscularly, with the second and third dose given one month and six months after the first dose respectively
Biological: Menactra TM
One dose of vaccine administered intramuscularly
Experimental: Cervarix Group
Subjects received Cervarix at Months 0, 1 and 6.
Biological: Different formulations of GSK Biologicals' HPV vaccine (580299)
Three doses of vaccine administered intramuscularly, with the second and third dose given one month and six months after the first dose respectively

  Eligibility

Ages Eligible for Study:   11 Years to 18 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes that they can, and will, comply with the requirements of the protocol should be enrolled in the study.
  • A female between, and including, 11 and 18 years of age at the time of the first vaccination.
  • Written informed consent obtained from parents/legally acceptable representative of the subject and written informed assent obtained from the subject if the subject is less than 18 years of age, or written informed consent obtained from the subject if the subject is 18 years of age.
  • Healthy subjects, as established by medical history and history-directed physical examination, before entering into the study.
  • Previously completed routine childhood vaccinations against diphtheria, tetanus and pertussis diseases, according to the recommended vaccination schedule at the time.
  • Subjects must have a negative urine pregnancy test.
  • Subjects of childbearing potential at the time of study entry are required to be abstinent or use adequate contraceptive precautions for 30 days prior to vaccination. Subjects also are required to agree to continue such precautions for two months after completion of the vaccination series. Female subjects who reach menarche (began menstruating) during the study and therefore become of child-bearing potential are required to agree to follow the same precautions.

Exclusion Criteria:

  • Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
  • Concurrently participating in another clinical study, at any time during the study period (up to the Month 12/13 visit), in which the subject has been or will be exposed to an investigational or a non-investigational product.
  • 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. 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.
  • A woman 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
  • Administration of a pre-school booster of diphtheria, tetanus, pertussis vaccine within the previous five years.
  • Administration of a diphtheria-tetanus booster or tetanus-diphteria-acellular pertussis (Tdap) vaccine within the previous five years.
  • Previous vaccination against Neisseria meningitidis.
  • Hypersensitivity to latex.
  • Cancer or autoimmune disease under treatment.
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine or following any other tetanus toxoid, diphtheria toxoid or pertussis-containing vaccine.
  • History of encephalopathy within seven days of administration of a previous dose of pertussis vaccine that is not attributable to another identifiable cause.
  • Progressive neurologic disorder, uncontrolled epilepsy or progressive encephalopathy.
  • Temperature of >= 105°F within 48 hours of receipt of a prior dose of diphteria- tetanu-pertussis (DTP) vaccine, not due to another identifiable cause.
  • Collapse or shock-like state within 48 hours of receipt of a prior dose of DTP vaccine.
  • Seizures with or without fever within three days of a prior dose of DTP vaccine.
  • Severe Arthus-type hypersensitivity reactions following a prior dose of tetanus toxoid within the previous 10 years.
  • Previous history of Guillain-Barré syndrome.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition
  • Acute disease at the time of enrolment. All vaccines can be administered to persons with a minor illness
  • Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
  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: NCT00369824

  Show 47 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Schwarz TF et al. AS04-adjuvanted cervial cancer vaccine : correlation between serum and mucosal anti-HPV-16 and anti-HPV-18 antibody levels. Abstract presented at FIGO 2009 - 19th World Congress of Gynecology & Obstetrics. Cape Town, South Africa, 4-9 October 2009.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00369824     History of Changes
Other Study ID Numbers: 107682
Study First Received: August 28, 2006
Results First Received: September 3, 2009
Last Updated: November 21, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
HPV
HPV, diptheria, pertussis, tetanus, meningitis

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on July 24, 2014