Follow-up Study to Evaluate the Safety and Immunogenicity of a HPV Vaccine (580299) in North America

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00546078
First received: October 17, 2007
Last updated: June 7, 2012
Last verified: March 2011
  Purpose

Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. This study will further evaluate induction of immune memory and anamnestic responses in women who previously took part in the primary study (580299/001) and follow-up study (580299/007). Subjects were aged 15-25 yrs at the time of entry into the primary study and participation in the follow-up study lasted approximately 6 years. In the primary and follow-up studies, subjects were protected against HPV-16 and HPV-18 endpoints and had sustained antibody responses to both vaccine types over at least 5.5 years of follow-up. All subjects from North American study sites that completed the follow-up study will be invited to take part in the current study. The study will evaluate the safety and immunogenicity of a dose of GSK Biologicals HPV vaccine (580299) in women who had been immunologically primed in the primary study.

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


Condition Intervention Phase
Human Papillomavirus (HPV) Infection
Papillomavirus Vaccines
Biological: Cervarix™
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Safety and Immunogenicity Study of an Additional Dose of HPV Vaccine (580299) in Young, Adult Women in North America.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Anti-human Papilloma Virus-16 (Anti-HPV-16) and Anti-HPV-18 Antibody Titers Greater Than or Equal to Pre-defined Cut-off Values [ Time Frame: At Day 7 and Month 1 (Day 30) ] [ Designated as safety issue: No ]
    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-HPV-16 and Anti-HPV-18 Antibody Titers [ Time Frame: At Day 7 and at Month 1 (Day 30) ] [ Designated as safety issue: No ]
    Titers are given as geometric mean titers (GMTs) calculated on all subjects.


Secondary Outcome Measures:
  • Number of Subjects With Anti-HPV-16 and Anti-HPV-18 Greater Than or Equal to Pre-defined Cut-off Values [ Time Frame: At Month 7 and Month 18 ] [ Designated as safety issue: No ]
    Cut-off values assessed include 8 EL.U/mL for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.

  • Anti-HPV-16 and Anti-HPV-18 Antibody Titers [ Time Frame: At Month 7 and Month 18 ] [ Designated as safety issue: No ]
    Titers are given as GMTs calculated on all subjects.

  • Number of Subjects With Antibody Titers Against Other Oncogenic HPV Types (HPV-31 & HPV-45) Greater Than or Equal to 59 EL.U/mL [ Time Frame: Day 0, Month 1 (Day 30), Month 7 and Month 18 ] [ Designated as safety issue: No ]
  • Anti-HPV-31 and Anti-HPV-45 Antibody Titers [ Time Frame: Day 7, Month 1 (Day 30), Month 7 and Month 18 ] [ Designated as safety issue: No ]
    Titers are given as geometric mean titers (GMTs) calculated on all subjects.

  • Number of Subjects With Cluster of Differentiation 4 (CD4) T Cell-mediated Immune Responses Specific to Defined Oncogenic HPV Types [ Time Frame: Day 0, Month 1 [Day 30], Month 7 and Month 18 ] [ Designated as safety issue: No ]

    CD4 T cell-mediated immune responses against the antigens HPV-16, HPV-18, HPV-31 and HPV-45 were analyzed for cells expressing at least 2 of the following immune markers: CD40 Ligand, Interleukin-2, Tumor Necrosis Factor alpha or Interferon-gamma.

    An immune response is defined as 500 or more antigen-specific CD4 T-cells per million CD4 T-cells.


  • Number of Subjects With Cluster of Differentiation 8 (CD8) T Cell-mediated Immune Responses Specific to Defined Oncogenic HPV Types [ Time Frame: Day 0, Month 1 [Day 30], Month 7 and Month 18 ] [ Designated as safety issue: No ]

    CD8 T cell-mediated immune responses against the antigens HPV-16, HPV-18, HPV-31 and HPV-45 were analyzed for cells expressing at least 2 of the following immune markers: CD40 Ligand, Interleukin-2, Tumor Necrosis Factor alpha or Interferon-gamma.

    An immune response is defined as 200 or more antigen-specific CD8 T-cells per million CD8 T-cells.


  • Number of Subjects With B Cell-mediated Immune Responses Specific to Defined Oncogenic HPV Types [ Time Frame: Day 0, Month 1 [Day 30], Month 7 and Month 18 ] [ Designated as safety issue: No ]

    B-cell-mediated immune responses against the antigens HPV-16, HPV-18, HPV-31 and HPV-45 were measured by Enzyme-linked immunosorbent spot (ELISPOT) assay.

    A memory B-cell immune response was defined as presence of any antigen-specific memory B-cells per million B-cells.


  • Number of Subjects Seropositive for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervico-vaginal Secretion Samples [ Time Frame: Day 0, Month 1 (Day 30), Month 7 and Month 18 ] [ Designated as safety issue: No ]

    Seropositivity was defined as the detection of antibody titers above the limit of quantification by Enzyme-Linked Immunosorbant Assay. Defining a cut-off is technically not possible for this assay.

    Analyses were done in all collected samples from the evaluable subjects who provided cervical samples, with < 200 erythrocytes per microliter.


  • Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies in Cervico-vaginal Secretion Samples [ Time Frame: Day 0, Month 1 (Day 30), Month 7 and Month 18 ] [ 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).

    Analyses were done in all collected samples from the evaluable subjects who provided cervical samples with < 200 erythrocytes per microliter.


  • Number of Subjects Reporting Solicited Local Symptoms [ Time Frame: Within 7 days after vaccination ] [ Designated as safety issue: No ]

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

    Solicited symptoms reported after the 4th vaccine dose in the 4-dose Group and across the 3 doses administered during this study in the 3-dose Group are disclosed.


  • Number of Subjects Reporting Solicited General Symptoms [ Time Frame: Within 7 days of vaccination ] [ Designated as safety issue: No ]

    Solicited general symptoms assessed include arthralgia, fatigue, fever, gastrointestinal discomfort, headache, myalgia, rash and urticaria.

    Solicited symptoms reported after the 4th vaccine dose in the 4-dose Group and across the 3 doses administered during this study in the 3-dose Group are disclosed.


  • Number of Subjects Reporting Unsolicited Adverse Events (AE) [ Time Frame: Within 30 days of vaccination ] [ Designated as safety issue: No ]

    An unsolicited adverse event is defined as 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.

    AEs reported after the 4th vaccine dose in the 4-dose Group and after the 3 doses administered in this study in the 3-dose Group are disclosed.


  • Outcome of Any Reported Pregnancies [ Time Frame: From Day 0 up to Month 18 ] [ Designated as safety issue: No ]
    Information on any subject who became pregnant while participating in this study was collected. The outcomes of the pregnancies are reported below.

  • Number of Subjects With New Onset of Chronic Diseases (NOCDs), New Onset of Autoimmune Diseases (NOADs) and Medically Significant Conditions (MSCs) [ Time Frame: From Day 0 up to Month 18 ] [ Designated as safety issue: No ]
    NOCDs include autoimmune disorders, asthma, type I diabetes, allergies. MSC include 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 Serious Adverse Events (SAEs) [ Time Frame: From Day 0 up to Month 18 ] [ 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: 116
Study Start Date: January 2008
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cervarix™ 4-Dose Group
Subjects who had received 3 doses of Cervarix™ in study 580299/001 (NCT00689741), received a 4th dose of Cervarix™ on Day 0 in the current study.
Biological: Cervarix™
Intramuscular injection, one or three doses
Other Name: GSK Biologicals' HPV Vaccine GSK580299
Experimental: Cervarix™ 3-Dose Group
Subjects who had received 3 doses of placebo in study 580299/001 (NCT00689741), received 3 doses of Cervarix™ (Day 0, Month 1 and Month 6) in the current study.
Biological: Cervarix™
Intramuscular injection, one or three doses
Other Name: GSK Biologicals' HPV Vaccine GSK580299

  Eligibility

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

Inclusion Criteria:

  • A subject whom the investigator believes that she can and will comply with the requirements of the protocol
  • Must have received three doses of study vaccine or placebo control in study 580299/001.
  • Must have completed study 580299/007.
  • Written informed consent must be obtained from the subject prior to enrollment in the study.
  • Healthy subjects, as established by medical history and history-directed clinical examination before entering into the study.
  • Subject must have a negative urine pregnancy test.
  • Subject must be at least three months post-termination of a pregnancy.
  • Subject must be of non-childbearing potential,or subjects are required to be abstinent or use adequate contraceptive precautions for 30 days prior to vaccination. Subjects are also required to agree to continue such precautions for two months after completion of the vaccination series.

Exclusion Criteria:

  • Pregnant or breastfeeding.
  • A woman planning to become pregnant or planning to discontinue contraceptive precautions during the study until approximately 2 months after the last vaccination.
  • 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.
  • 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 of each dose of vaccine. Administration of some routine vaccines up to 8 days before each dose of study vaccine is allowed.
  • 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 outside of protocol 580299/001.
  • Any medically diagnosed or suspected immunosuppressive or 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
  • Acute or chronic, clinically significant pulmonary, cardiovascular, neurologic, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
  • Cancer or autoimmune disease under treatment.
  • Administration of immunoglobulins and/or any blood products within the three months (90 days) preceding enrollment or planned administration during the study period.
  • Acute disease at the time of enrollment. All vaccines can be administered to persons with a minor illness
  • Heavy bleeding or heavy vaginal discharge in which a pelvic exam cannot be performed.
  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: NCT00546078

Locations
United States, California
GSK Investigational Site
San Francisco, California, United States, 94118
United States, Georgia
GSK Investigational Site
Augusta, Georgia, United States, 30912-3500
United States, Kentucky
GSK Investigational Site
Bardstown, Kentucky, United States, 40004
GSK Investigational Site
Louisville, Kentucky, United States, 40202
United States, New Mexico
GSK Investigational Site
Albuquerque, New Mexico, United States, 87131
United States, Pennsylvania
GSK Investigational Site
Grove City, Pennsylvania, United States, 16127
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19107
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15241
United States, Texas
GSK Investigational Site
San Antonio, Texas, United States, 78205
United States, Utah
GSK Investigational Site
Salt Lake City, Utah, United States, 84109
United States, Washington
GSK Investigational Site
Seattle, Washington, United States, 98105
United States, Wisconsin
GSK Investigational Site
Marshfield, Wisconsin, United States, 54449
Canada, Alberta
GSK Investigational Site
Edmonton, Alberta, Canada, T6G 2C8
Canada, British Columbia
GSK Investigational Site
Langley, British Columbia, Canada, V3A 4H9
Canada, Manitoba
GSK Investigational Site
Winnipeg, Manitoba, Canada, R3E 0J9
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Moscicki B et al. Anamnestic response elicited by a fourth dose of the HPV-16/18 ASO4-adjuvanted vaccine in young women. Abstract presented at European Research Organization on Genital Infection and Neoplasia 2010 (EUROGIN). Monte Carlo, Monaco, 17-20 February 2010.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00546078     History of Changes
Other Study ID Numbers: 109628
Study First Received: October 17, 2007
Results First Received: November 12, 2009
Last Updated: June 7, 2012
Health Authority: Canada: Biologics and Genetic Therapies Directorate (BGTD)
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
HPV vaccine
Cervical cancer
Human papillomavirus infection

ClinicalTrials.gov processed this record on September 14, 2014