Evaluation of Immunogenicity and Safety of Two 2-dose Human Papillomavirus (HPV) Vaccine Schedules in 9-14 Year Old Girls

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01381575
First received: June 17, 2011
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

This study has been designed to evaluate the immunogenicity and safety of GSK Biologicals' HPV-16/18 vaccine when administered according to alternative 2-dose schedules (0,6 months and 0,12 months) in healthy 9-14 year old females as compared to the standard 3-dose schedule (0,1,6 months) in 15-25 year old females.


Condition Intervention Phase
Infections, Papillomavirus
Biological: GSK Biologicals' HPV vaccine 580299
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' HPV-16/18 L1 AS04 Vaccine When Administered According to Alternative 2-dose Schedules in 9 - 14 Year Old Females

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 [ Time Frame: 1 month after the last dose of study vaccine (Month 7) ] [ Designated as safety issue: No ]
    Seroconversion was defined as the appearance of antibodies (anti-HPV-16 titres ≥ 8 ELISA units per millilitre (EL.U/mL) and anti-HPV-18 titres ≥ 7 EL.U/mL) in the serum of subjects seronegative before vaccination. A seronegative subject was a subject with anti-HPV-16/18 antibody concentration < 8/7 EL.U/mL. A seropositive subject was a subject with anti-HPV-16/18 antibody concentration ≥ 8/7 EL.U/mL.

  • Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA). [ Time Frame: 1 month after the last dose of study vaccine (Month 7) ] [ Designated as safety issue: No ]
    Antibody concentrations were and expressed as geometric mean concentrations (GMCs) and expressed as enzyme-linked immunosorbent assay [ELISA] units per millilitre (EL.U/mL), with the cut-off values of 8 EL.U/mL for HPV-016 and 7 EL.U/mL for HPV-018.


Secondary Outcome Measures:
  • Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies [ Time Frame: At Day 0 and Months 7, 12, 18, 24 and 36 ] [ Designated as safety issue: No ]

    Seroconversion was defined as the appearance of antibodies (anti-HPV-16 titres ≥ 8 EL.U/mL and anti-HPV-18 titres ≥ 7 EL.U/mL) in the serum of subjects seronegative before vaccination. A seronegative subject was a subject with anti-HPV-16/18 antibody concentration < 8/7 EL.U/mL. A seropositive subject was a subject with anti-HPV-16/18 antibody concentration ≥ 8/7 EL.U/mL.

    Note: Results for Months 12, 24 and 36 will be updated when they become available.


  • Anti-HPV-16 and Anti-HPV-18 Antibody Titres (by Pseudovirion-Based Neutralisation Assay [PBNA]) [ Time Frame: At Day 0 and Months 7, 12, 18, 24 and 36 ] [ Designated as safety issue: No ]

    Antibody titers were given as Geometric mean titers (GMTs). The cut-off of the assay were ≥ 40 ED50 for anti-HPV-16 and anti-HPV-18.

    Note: Results for Months 12, 24 and 36 will be updated when they become available.


  • Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA). [ Time Frame: At Day 0 and Months 7, 12, 24 and 36 ] [ Designated as safety issue: No ]
    Antibody concentrations were expressed as geometric mean titers (GMTs) and given in EL.U/mL, with the cut-off values of ≥ 8 ELISA units per millilitre (EL.U/mL) for HPV-016 and ≥ 7 EL.U/mL for HPV-018Note: Results for Months 12, 24 and 36 will be updated when they become available.

  • Cell-mediated Immunogenicity Related to Anti-HPV-16 Specific T Cell-mediated Immune Response (CMI) [ Time Frame: At Day 0 and Months 7, 12, 24 and 36 ] [ Designated as safety issue: No ]

    The CMI response was the measure of the cytokines production [i.e.interleukin-2 (IL-2), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α) and cluster of differentiation 40 Ligand (CD40L)] by HPV-antigen specific T lymphocytes and measured by intracellular cytokine staining (ICS) assay for HPV-16 The frequency was presented as number of of cytokine-positive cluster of differentiation (CD)4 i.e.CD4+/CD8+ cells per million CD4+/CD8+ cells.

    All doubles= T cell expressing at least 2 cytokines. Results were tabulated by the pre-vaccination status of the subjects, where S- = seronegative subjects (antibody titre lower than the cut-off value of 8 EL.U/mL) prior to vaccination. S+ = seropositive subjects (antibody titre ≥ 8 El.U/mL) prior to vaccination.

    Note: Results for Months 12, 24 and 36 will be updated once they become available.


  • Cell-mediated Immunogenicity Related to Anti-HPV-18 Specific T Cell-mediated Immune Response (CMI) [ Time Frame: At Day 0 and Months 7, 12, 24 and 36 ] [ Designated as safety issue: No ]

    The CMI response was the measure of the cytokines production [IL-2, IFN-γ, TNF-α and CD40L] by HPV-antigen specific T lymphocytes and measured by intracellular cytokine staining (ICS) assay for HPV-18. The frequency was presented as number of cytokine-producing CD4+/CD8+ cells per million CD4+/CD8+ cells.

    All doubles= T cell expressing at least 2 cytokines. Results were tabulated by the pre-vaccination status of the subjects, where S- = seronegative subjects (antibody titre lower than the cut-off value of 7 EL.U/mL) prior to vaccination. S+ = seropositive subjects (antibody titre ≥ 7 EL.U/mL) prior to vaccination.

    Note: Results for Months 12, 24 and 36 will be updated once they become available.


  • Number of Subjects With Any and Grade 3 Solicited Local Symptoms. [ Time Frame: During the 7-day period (Days 0-6) following any vaccination ] [ Designated as safety issue: No ]
    Assessed solicited local symptoms were pain, redness and swelling. Any = Occurrence of any solicited local symptom regardless of their intensity grade. Grade 3 pain = Significant pain at rest, that prevented normal every day activity. Grade 3 redness/swelling = Redness/swelling above 50 millimeters (mm).

  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. [ Time Frame: During the 7-day period (Days 0-6) following any vaccination ] [ Designated as safety issue: No ]
    Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, fever and urticaria. Any = Occurrence of any solicited general symptom regardless of intensity grade or relationship to vaccination. Any Fever = Axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C). Grade 3 symptom = Symptom that prevented normal activity. Grade 3 fever = Fever > 39.0 °C. Related = General symptom assessed by the investigator as causally related to the vaccination.

  • Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [ Time Frame: During the 30-day (Days 0-29) post vaccination period ] [ Designated as safety issue: No ]
    An unsolicited AE covers 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 and 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. Any = Any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 = Unsolicited AE preventing normal activity. Related = Unsolicited AE assessed by the investigator as causally related to the study vaccination.

  • Number of Subjects With Any Potential Immune-Mediated Diseases (pIMDs) [ Time Frame: From Day 0 up to Months 7, 12, 24 and 36 ] [ Designated as safety issue: No ]

    pIMDs are a subset of AEs that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology.

    Note: Results up to Months 12, 24 and 36 will be updated once they become available.


  • Number of Subjects With Medically Significant Conditions (MSCs) [ Time Frame: From Day 0 to Months 7, 12, 24 and 36 ] [ Designated as safety issue: No ]

    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.

    Note: Results up to Months 12, 24 and 36 will be updated once they become available.


  • Number of Subjects With Any Serious Adverse Events (SAEs) [ Time Frame: From Day 0 up to Months 7, 12, 24 and 36 ] [ Designated as safety issue: No ]

    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

    Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.

    Note: Results up to Months 12, 24 and 36 will be updated once they become available.


  • Number of Subjects Completing the Vaccination Schedule [ Time Frame: Up to Month 7 ] [ Designated as safety issue: No ]
    The number of subjects completing the vaccination course was assessed as the number of subjects with at least one dose received during the study.

  • Number of Subjects With Pregnancies Ongoing and Their Outcome [ Time Frame: From Day 0 up to Months 7, 12, 24 and 36 ] [ Designated as safety issue: No ]
    Specific pregnancy outcomes were elective termination with apparent congenital anomaly and ectopic pregnancy. Note: Results for Months 12, 24 and 36 will be updated once they become available.

  • Cell-mediated Immunogenicity Related to Anti-HPV-16 Specific B Cell-mediated Immune Response [ Time Frame: At Day 0 and Months 7, 12, 24 and 36 ] [ Designated as safety issue: No ]

    The cell-mediated immune response was assessed as being the frequency of B-cell memory of HPV-16 antigen-specific memory B-cells per million memory B-cells in subjects with detectable B-cells. The results are presented by pre-vaccination status, where S- = seronegative subjects (antibody concentration < 8 EL.U/mL) prior to vaccination and S+ = seropositive subjects (antibody concentration ≥ 8 EL.U/mL) prior to vaccination.

    Note:Results for Months 12, 24 and 36 will be updated once they become available.


  • Cell-mediated Immunogenicity Related to Anti-HPV-18 Specific B Cell-mediated Immune Response [ Time Frame: At Day 0 and Months 7, 12, 24 and 36 ] [ Designated as safety issue: No ]

    The cell-mediated immune response was assessed as being the frequency of B-cell memory of HPV-18 antigen-specific memory B-cells per million memory B-cells in subjects with detectable B-cells. The results are presented by pre-vaccination status, where S- = seronegative subjects (antibody concentration < 7 EL.U/mL) prior to vaccination and S+ = seropositive subjects (antibody concentration ≥ 7 EL.U/mL) prior to vaccination.

    Note: Results for Months 12, 24 and 36 will be updated once they become available.



Enrollment: 1447
Study Start Date: June 2011
Estimated Study Completion Date: December 2014
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cervarix 1 Group
Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Months 0 and 6. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.
Biological: GSK Biologicals' HPV vaccine 580299
Subjects will receive 2 or 3 doses of HPV vaccine administered intramuscularly
Other Name: Cervarix™
Experimental: Cervarix 2 Group
Female subjects aged 15 to 25 years at the time of the first vaccination, who received 3 doses of the Cervarix vaccine at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.
Biological: GSK Biologicals' HPV vaccine 580299
Subjects will receive 2 or 3 doses of HPV vaccine administered intramuscularly
Other Name: Cervarix™
Experimental: Cervarix 3 Group
Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Months 0 and 12. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.
Biological: GSK Biologicals' HPV vaccine 580299
Subjects will receive 2 or 3 doses of HPV vaccine administered intramuscularly
Other Name: Cervarix™

  Eligibility

Ages Eligible for Study:   9 Years to 25 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes can and will comply with the requirements of the protocol or/ and subjects who the investigator believes their parent(s)/Legally Acceptable Representative(s) [LAR(s)] can and will comply with the requirements of the protocol
  • A female between, and including, 9 and 25 years of age at the time of the first vaccination
  • Written informed consent obtained from the subject/from the parent(s)/LAR(s) of the subject prior to enrolment in the study. In addition, subjects below the legal age of consent should sign and personally date a written informed assent form
  • Healthy subjects
  • Female subjects of non-childbearing potential may be enrolled in the study
  • Female subjects of childbearing potential may be enrolled in the study, if the subject:

    • has practiced adequate contraception for 30 days prior to vaccination, and
    • has a negative pregnancy test on the day of vaccination, and
    • has agreed to continue adequate contraception during the entire vaccination period and up to two months after the last study vaccine dose

Exclusion Criteria:

  • Pregnant or breastfeeding
  • A female planning to become pregnant, likely to become pregnant or planning to discontinue contraceptive precautions during the entire vaccination period and up to two months after the last study vaccine dose
  • Previous vaccination against HPV or planned administration of another HPV vaccine during the study
  • Child in care. A child in care is a child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. The definition of a child in care does not include a child who is adopted or has an appointed legal guardian.
  • 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. History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccines
  • Cancer or autoimmune disease under treatment
  • Planned administration/administration of a vaccine/product not foreseen by the study protocol within 30 days before each dose of vaccine. Administration of routine meningococcal, hepatitis B, hepatitis A, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccine up to 8 days before each dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window
  • 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
  • Previous administration of MPL or AS04 adjuvant.
  • 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
  • Any confirmed or suspected immunosuppressive or immunodeficient condition
  • Family history of congenital or hereditary immunodeficiency
  • Major congenital defects or serious chronic illness
  • Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests, which in the opinion of the investigator precludes administration of the study vaccine
  • Acute disease and/or fever at the time of enrolment
  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: NCT01381575

Locations
Canada, British Columbia
GSK Investigational Site
Coquitlam, British Columbia, Canada, V3K 3P4
Canada, Nova Scotia
GSK Investigational Site
Halifax, Nova Scotia, Canada, B3K 6R8
Canada, Ontario
GSK Investigational Site
Sudbury, Ontario, Canada, P3E 1H5
GSK Investigational Site
Toronto, Ontario, Canada, M9W 4L6
GSK Investigational Site
Woodstock, Ontario, Canada, N4S 5P5
Canada, Quebec
GSK Investigational Site
Sherbrooke, Quebec, Canada, J1H 2G2
Germany
GSK Investigational Site
Freiburg, Baden-Wuerttemberg, Germany, 79106
GSK Investigational Site
Kehl, Baden-Wuerttemberg, Germany, 77694
GSK Investigational Site
Berchtesgaden, Bayern, Germany, 83471
GSK Investigational Site
Wuerzburg, Bayern, Germany, 97070
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30657
GSK Investigational Site
Wolfenbuettel, Niedersachsen, Germany, 38302
GSK Investigational Site
Wolfsburg, Niedersachsen, Germany, 38440
GSK Investigational Site
Kleve-Materborn, Nordrhein-Westfalen, Germany, 47533
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55116
GSK Investigational Site
Trier, Rheinland-Pfalz, Germany, 54290
GSK Investigational Site
Flensburg, Schleswig-Holstein, Germany, 24937
GSK Investigational Site
Weimar, Thueringen, Germany, 99425
GSK Investigational Site
Berlin, Germany, 13055
GSK Investigational Site
Hamburg, Germany, 22159
Italy
GSK Investigational Site
Genova, Liguria, Italy, 16132
GSK Investigational Site
Milano, Lombardia, Italy, 20122
GSK Investigational Site
Cuneo, Piemonte, Italy, 12100
GSK Investigational Site
Cagliari, Sardegna, Italy, 09127
GSK Investigational Site
Ragusa, Sicilia, Italy, 97100
GSK Investigational Site
Padova, Veneto, Italy, 35128
Taiwan
GSK Investigational Site
Taipei, Taiwan
GSK Investigational Site
Taipei, Taiwan, 100
GSK Investigational Site
Taoyuan, Taiwan, 333
Thailand
GSK Investigational Site
Bangkok, Thailand, 10330
GSK Investigational Site
Chiangmai, Thailand, 50200
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01381575     History of Changes
Other Study ID Numbers: 114700
Study First Received: June 17, 2011
Results First Received: June 28, 2013
Last Updated: January 30, 2014
Health Authority: Thailand: Institutional Review Board, Faculty of Medicine, Chulalongkorn University
Taiwan: Food and Drug Administration, Department of Health, Executive Yuan
Canada: Health Canada, Health Products and Food Branch, Biologics and Genetic Therapies Directorate
Thailand: Research Ethics committee, Faculty of Medicine, Chiang Mai University
Italy: A.I.F.A.: Agenzia Italiana del Farmaco (Italian Agency for Medicines)
Germany: Paul Ehrlich Institute

Keywords provided by GlaxoSmithKline:
HPV infection
Human Papillomavirus
Cervical cancer
HPV-16
HPV-18
vaccine

ClinicalTrials.gov processed this record on July 26, 2014