Evaluation of Immunogenicity and Safety of Human Papillomavirus (HPV) Vaccine Co-administered With Another Vaccine in Healthy Female Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00652938
First received: March 27, 2008
Last updated: December 19, 2013
Last verified: April 2013
  Purpose

Infection with human papillomavirus (HPV) has been clearly established as the necessary 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. Thus, HPV vaccination could complement the existing pre-adolescent/adolescent vaccination programs. This Phase IIIb study is designed to evaluate the immunogenicity and safety of co-administering a commercially available vaccine with GSK Biologicals' HPV-16/18 L1 VLP AS04 (Cervarix TM) vaccine as compared to the administration of either vaccine alone.


Condition Intervention Phase
Infections, Papillomavirus
Biological: HPV Vaccine (GSK580299) Cervarix TM
Biological: Engerix B
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 GlaxoSmithKline Biologicals' HPV Vaccine (580299) Co-administrated 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 With Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Value for Seroprotection [ Time Frame: Month 7 ] [ Designated as safety issue: No ]

    Only groups which had received the HBV vaccine were included in the analysis.

    Subjects included were seronegative for anti-HBs (antibody titer < 3.3 milli International Units per milliliter (mIU/mL)) prior to vaccination.

    Anti-HBs antibody cut-off value for seroprotection assessed included 10 mIU/mL.


  • Number of Subjects With Anti-human Papillomavirus 16 and 18 (Anti-HPV-16 and Anti-HPV-18) Antibody Concentrations Above the Cut-off Value for Seroconversion [ Time Frame: Month 7 ] [ Designated as safety issue: No ]

    Only groups which had received the HPV vaccine were included in the analysis.

    Anti-HPV-16 antibody cut-off value assessed included 8 Enzyme-linked Immunosorbent Assay (ELISA) units per milliliter (EL.U/mL) and anti-HPV-18 antibody cut-off value assessed included 7 EL.U/mL.

    Subjects included were seronegative for anti-HPV-16 (antibody titer < 8 EL.U/mL) and anti-HPV-18 (antibody titer < 7 EL.U/mL) prior to vaccination.


  • Anti-HPV-16/18 Antibody Titres [ Time Frame: Month 7 ] [ Designated as safety issue: No ]

    Antibody titers for Anti-HPV-16 and Anti-HPV-18 are expressed as Geometric Mean Titers (GMTs).

    Only groups which had received the HPV vaccine were included in the analysis.

    Subjects included were seronegative for anti-HPV-16 (antibody titer < 8 EL.U/mL) and anti-HPV-18 (antibody titer < 7 EL.U/mL) prior to vaccination.



Secondary Outcome Measures:
  • Number of Subjects With Anti-HBs Antibody Concentrations Above the Cut-off Value for Seroconversion [ Time Frame: Month 7 ] [ Designated as safety issue: No ]

    Only groups which had received the HBV vaccine were included in the analysis.

    Subjects included were seronegative for anti-HBs (antibody titer < 3.3 mIU/mL) prior to vaccination.

    Anti-HBs antibody cut-off value for seroconversion assessed included 3.3 mIU/mL.


  • Anti-HBs Antibody Titres [ Time Frame: Month 7 ] [ Designated as safety issue: No ]

    Antibody titers for anti-HBs are given as Geometric Mean Titers (GMTs) in mIU/mL.

    Only groups which had received the HBV vaccine were included in the analysis.

    Subjects included were seronegative for anti-HBs (antibody titer < 3.3 mIU/mL) prior to vaccination.


  • Number of Subjects With Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations Above the Cut-off Value for Seroconversion [ Time Frame: Month 2 ] [ Designated as safety issue: No ]

    Only groups which had received the HPV vaccine were included in the analysis.

    Anti-HPV-16 antibody cut-off value assessed included 8 Enzyme-linked Immunosorbent Assay (ELISA) units per milliliter (EL.U/mL) and anti-HPV-18 antibody cut-off value assessed included 7 EL.U/mL.

    Subjects included were seronegative for anti-HPV-16 (antibody titer < 8 EL.U/mL) and anti-HPV-18 (antibody titer < 7 EL.U/mL) prior to vaccination.


  • Anti-HPV-16/18 Antibody Titres [ Time Frame: Month 2 ] [ Designated as safety issue: No ]

    Antibody titers for Anti-HPV-16 and Anti-HPV-18 are expressed as Geometric Mean Titers (GMTs).

    Only groups which had received the HPV vaccine were included in the analysis.

    Subjects included were seronegative for anti-HPV-16 (antibody titer < 8 EL.U/mL) and anti-HPV-18 (antibody titer < 7 EL.U/mL) prior to vaccination.


  • Number of Subjects With Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Value for Seroconversion [ Time Frame: Month 2 ] [ Designated as safety issue: No ]

    Only groups which had received the HBV vaccine were included in the analysis.

    Subjects included were seronegative for anti-HBs (antibody titer < 3.3 mIU/mL) prior to vaccination.

    Anti-HBs antibody cut-off value for seroconversion assessed included 3.3 mIU/mL.


  • Number of Subjects With Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Value for Seroprotection [ Time Frame: Month 2 ] [ Designated as safety issue: No ]

    Only groups which had received the HBV vaccine were included in the analysis.

    Subjects included were seronegative for anti-HBs (antibody titer < 3.3 milli International Units per milliliter (mIU/mL)) prior to vaccination vaccination.

    Anti-HBs antibody cut-off value for seroprotection assessed included 10 mIU/mL.


  • Anti-HBs Antibody Titers [ Time Frame: Month 2 ] [ Designated as safety issue: No ]

    Anti-HBs antibody titers are given as GMTs in mIU/mL.

    Only groups which had received the HBV vaccine were included in the analysis.

    Subjects included were seronegative for anti-HBs (antibody titer < 3.3 mIU/mL) prior to vaccination.


  • Number of Subjects Reporting Any Solicited Local Symptoms [ Time Frame: During the 7-day period (Days 0 - 6) following vaccination ] [ Designated as safety issue: No ]

    Solicited local symptoms included injection site pain, redness and swelling.

    Any solicited local symptom is occurence of a symptom regardless of its intensity.


  • Number of Subjects Reporting Grade 3 Solicited Local Symptoms [ Time Frame: During the 7-day period (Days 0-6) following vaccination ] [ Designated as safety issue: No ]

    Solicited local symptoms include injection site pain, redness and swelling.

    Grade 3 pain is pain that prevented normal everyday activities. Grade 3 redness is redness that was > 50 mm. Grade 3 swelling is swelling that was > 50 mm.


  • Number of Subjects Reporting Any Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) period following vaccination. ] [ Designated as safety issue: No ]

    Solicited general symptoms included arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, temperature in degrees celsius (axillary) and urticaria.

    Any solicited general symptom is the occurence of the symptom regardless of its intensity or relationship to study vaccination.


  • Number of Subjects Reporting Grade 3 Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) period following vaccination ] [ Designated as safety issue: No ]

    Solicited general symptoms included arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, temperature in degrees celsius (axillary) and urticaria.

    Grade 3 arthralgia, fatigue, gastrointestinal, headache, myalgia and rash were symptoms that prevented normal activity.

    Grade 3 temperature was temperature > 39 degrees Celsius. Grade 3 urticaria was urticaria distributed on at least 4 body areas.


  • Number of Subjects Reporting Related Solicited General Symptoms [ Time Frame: During the 7-day period (Days 0 - 6) following vaccination ] [ Designated as safety issue: No ]

    Solicited general symptoms included arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, temperature in degrees celsius (axillary) and urticaria.

    Related solicited general symptoms were those symptoms assessed by the investigators as related to the study vaccination.


  • Number of Subjects Reporting Any, Grade 3 and Causally Related to Vaccination Unsolicited Adverse Events (AEs) [ Time Frame: During the 30-day period (Days 0 - 29) following any vaccination ] [ Designated as safety issue: No ]

    Unsolicited AE covers any AE 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.

    Grade 3 AE was an AE that prevented normal activities. Related AE was an AE that was assessed by the investigator as related to the study vaccination.


  • Number of Subjects Reporting Any and Causally Related to Vaccination Serious Adverse Events (SAEs) [ Time Frame: Throughout the active phase of the study (up to Month 7). ] [ 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.

    Related SAEs were SAEs assessed by the investigators as related to the vaccination.

    * Grade 3 SAEs were not assessed.


  • Number of Subjects Reporting Any and Causally Related to Vaccination SAEs [ Time Frame: Throughout the safety follow-up (month 7 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.

    * Grade 3 SAEs were not assessed.


  • 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 (i.e., AEs prompting emergency room or physician visits that are not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that are not related to common diseases).

  • Number of Subjects Reporting Medically Significant Conditions [ Time Frame: Throughout the safety follow-up (month 7 up to Month 12) ] [ Designated as safety issue: No ]
    Medically significant conditions (i.e., AEs prompting emergency room or physician visits that are not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that are not related to common diseases).


Enrollment: 744
Study Start Date: April 2008
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cervarix & Engerix Group
Subjects received 3 doses of Cervarix™ (Human Papillomavirus [HPV] vaccine) co-administered with Engerix™ (Hepatitis B [HBV] vaccine) according to a 0, 1, 6-month schedule.
Biological: HPV Vaccine (GSK580299) Cervarix TM
IM administration
Biological: Engerix B
IM administration
Experimental: Cervarix Group
Subjects received 3 doses of Cervarix™ (Human Papillomavirus [HPV] vaccine) according to a 0, 1, 6-month schedule.
Biological: HPV Vaccine (GSK580299) Cervarix TM
IM administration
Active Comparator: Engerix Group
Subjects received 3 doses of Engerix™ (Hepatitis B [HBV] vaccine) according to a 0, 1, 6-month schedule.
Biological: Engerix B
IM administration

  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 parents/legally acceptable representatives (LARs) can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits) 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's parent/LAR prior to the enrolment. In addition, 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. Absence of pregnancy should be verified with a urine pregnancy test.
  • If the subject is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for at least 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series. Subjects who reach menarche (begin menstruating) during the study, and therefore become of childbearing potential, must agree to follow the same precautions.

Exclusion Criteria:

  • 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.
  • 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 such as meningococcal, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccines up to 8 days before the first dose of study vaccine is allowed.
  • 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).
  • A subject planning to become pregnant, likely to become pregnant (as determined by the investigator) 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 B or planned administration of any hepatitis B vaccine other than that foreseen by the study protocol during the study period.
  • History of hepatitis B infection.
  • Known exposure to hepatitis 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
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: NCT00652938

Locations
Netherlands
GSK Investigational Site
Nijmegen, Netherlands, 6525 GA
GSK Investigational Site
Rotterdam, Netherlands, 3011 EN
Sweden
GSK Investigational Site
Linköping, Sweden, SE-581 85
GSK Investigational Site
Luleå, Sweden, SE-972 31
GSK Investigational Site
Malmö, Sweden, SE-211 52
GSK Investigational Site
Norrköping, Sweden, SE-601 82
GSK Investigational Site
Skene, Sweden, SE-511 62
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: NCT00652938     History of Changes
Other Study ID Numbers: 111507
Study First Received: March 27, 2008
Results First Received: August 4, 2010
Last Updated: December 19, 2013
Health Authority: Sweden: Medical Products Agency

Keywords provided by GlaxoSmithKline:
Co-administration
HPV vaccine
Cervical cancer

ClinicalTrials.gov processed this record on August 21, 2014