Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' Human Papillomavirus (HPV) Vaccine (GSK-580299) and Merck's Gardasil® Vaccine When Administered According to Alternative 2-dose Schedules in 9-14 Year Old Females

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01462357
First received: October 27, 2011
Last updated: February 25, 2016
Last verified: November 2015
  Purpose
The purpose of this study is to evaluate the immunogenicity and the safety of Cervarix administered according to a 2-dose schedule at 0, 6 months compared to Gardasil, administered according to a 2-dose schedule at 0, 6 months or the standard 3-dose schedule of 0, 2, 6 months in 9-14 years old healthy females.

Condition Intervention Phase
Infections, Papillomavirus
Biological: Cervarix
Biological: Gardasil
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' HPV-16/18 L1 AS04 Vaccine and Merck's Gardasil® 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 Seroconverted Subjects for Anti-HPV-16/18, as Assessed by ELISA [ Time Frame: One month after the last dose of study vaccine (Month 7) ] [ Designated as safety issue: No ]
    Seroconversion was defined as the appearance of antibodies (i.e. anti-HPV-16 and anti-HPV-18 antibody titers respectively greater than or equal to 19 and 18 EL.U/mL) in the serum of subjects seronegative before vaccination in the primary study.

  • Anti-HPV-16/18 Antibody Concentrations Assessed by ELISA [ Time Frame: One month after the last dose of study vaccine (Month 7) ] [ Designated as safety issue: No ]
    Anti-HPV 16/18 antibody concentrations were presented as geometric mean concentration (GMC) and expressed in ELISA units per milliliter (EL.U/mL) based on an enzyme-linked immunosorbent assay (ELISA).


Secondary Outcome Measures:
  • Anti-HPV-16/18 Seroconversion Rates Assessed by ELISA [ Time Frame: At Day 0 and Months 12, 18, 24 and 36 ] [ Designated as safety issue: No ]
    At the time of posting this record, the results for Month 36 were not available. The record will be updated when the additional validated results are available.

  • Anti-HPV-16/18 Antibody Concentrations Assessed by ELISA [ Time Frame: At Day 0 and Months 12, 18, 24 and 36 ] [ Designated as safety issue: No ]

    Anti-HPV 16/18 antibody concentrations were presented as geometric mean concentration (GMC) and expressed in ELISA units per milliliter (EL.U/mL) based on an enzyme-linked immunosorbent assay (ELISA).

    At the time of posting this record, the results for Month 36 were not available. The record will be updated when the additional validated results are available.


  • Anti-HPV-16/18 Seroconversion Rates Assessed by Pseudovirion-based Neutralization Assay (PBNA) in a Subset of Subjects [ Time Frame: At Day 0 and Months 7, 12, 18, 24 and 36 ] [ Designated as safety issue: No ]
    At the time of posting this record, the results for Months 24 and 36 were not available. The record will be updated when the additional validated results are available.

  • Anti-HPV-16/18 Antibody Titers Assessed by PBNA in a Subset of Subjects [ Time Frame: At Day 0 and Months 7, 12, 18, 24 and 36 ] [ Designated as safety issue: No ]

    Anti-HPV 16/18 antibody titers were presented as geometric mean titers (GMT) and expressed in titers using the pseudovirion-based neutralization assay (PNBA).

    At the time of posting this record, the results for Months 24 and 36 were not available. The record will be updated when the additional validated results are


  • T-cell-mediated Immune Responses in the Sub-cohort for CMI [ Time Frame: At Day 0 and Months 7, 12, 24 and 36 ] [ Designated as safety issue: No ]
    At the time of posting this record, the results for Month 36 were not available. The record will be updated when the additional validated results are available.

  • B-cell-mediated Immune Responses in the Sub-cohort for CMI [ Time Frame: At Day 0 and Months 7, 12, 24 and 36 ] [ Designated as safety issue: No ]

    The frequency of B-cell Elispot response to HPV-16/18 by overall status was presented.

    At the time of posting this record, the results for Month 36 were not available. The record will be updated when the additional validated results are available


  • Number of Subjects With Any, Grade 3 and Related Solicited Local Symptoms. [ Time Frame: During the 7-day period (Days 0-6) following vaccination (across doses) ] [ Designated as safety issue: No ]

    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimetres (mm) of injection site. Relationship analysis was not performed.

    Note: Grade 3 symptoms are not presented since cases are still unblinded due to the study being ongoing. They will be added once results become available.


  • Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms. [ Time Frame: During the 7-day period (Days 0-6) following vaccination (across doses) ] [ Designated as safety issue: No ]

    Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, temperature [defined as oral temperature equal to or above 37.5 degrees Celsius (°C)] and urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

    Note: Grade 3 symptoms are not presented since cases are still unblinded due to the study being ongoing. They will be added once results become available.


  • Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs). [ Time Frame: During the 30-day period (Days 0-29) post-vaccination ] [ 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 was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.

  • Number of Subjects With Potentially Immune Mediated Diseases (pIMDs) [ Time Frame: From Day 0 to Month 36 (throughout the study period) ] [ Designated as safety issue: No ]
    Note: Results beyond Month 24 will be updated when validated results become available

  • Number of Subjects With Medically Significant Conditions (MSCs) [ Time Frame: From Day 0 to Month 36 (throughout the study period) ] [ Designated as safety issue: No ]

    MSCs were defined as AEs prompting emergency room (ER) or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs not related to common diseases. Common diseases include: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.

    Note: Results beyond Month 24 will be updated when validated results become available


  • Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: From Day 0 to Month 36 (throughout the study period) ] [ 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.

    Note: SAEs were not listed as they remain blinded until the end of the study.


  • Number of Subjects Starting a Concomitant Medication [ Time Frame: During the 30-day (Days 0-29) post-vaccination period ] [ Designated as safety issue: No ]

    The outcome presents the number of subjects starting any concomitant medication, as well as any antipyretic, any prophylactic antipyretic and any antibiotic.

    Note: The number of subjects starting any prophylactic antipyretic is blinded at the time of posting this record. The record will be updated once it becomes available.


  • Number of Subjects Starting a Concomitant Medication [ Time Frame: From Day 0 to Month 36 (throughout the study period) ] [ Designated as safety issue: No ]

    The outcome presents the number of subjects starting any concomitant medication, as well as any antipyretic, any prophylactic antipyretic and any antibiotic.

    Note: The number of subjects starting any prophylactic antipyretic is blinded at the time of posting this record. The record will be updated once it becomes available.

    Results for timepoints beyond Month 24 will be added once they become available.


  • Number of Subjects Completing the Vaccination Schedule [ Time Frame: Throughout the study period (From Day 0 up to Month 36) ] [ Designated as safety issue: No ]
  • Number of Subjects With Pregnancies [ Time Frame: Throughout the study period (From Day 0 up to Month 36) ] [ Designated as safety issue: No ]
    Note: No pregnancies were reported up to the Month 12 time point. Results beyond Month 24 will be updated when validated results become available


Enrollment: 1079
Study Start Date: November 2011
Study Completion Date: October 2015
Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cervarix 2 dose Group
Subjects who received 2 doses of CervarixTM vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Biological: Cervarix
2 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Day 0 and Month 6
Drug: placebo
2 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 2 to maintain blinding
Experimental: Gardasil 2 dose Group
Subjects who received 2 doses of Gardasil® vaccine at Day 0 and Month 6 and 1 dose of placebo at Month 2. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Biological: Gardasil
2 or 3 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes or vials to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Day 0 and Month 6 (Gard_2D) or at Day 0, Month 2 and Month 6 (Gard_3D), respectively.
Drug: placebo
2 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Month 2 to maintain blinding
Experimental: Gardasil 3 dose Group
Subjects who received 3 doses of Gardasil® vaccine at Day 0 and at Months 2 and 6. The vaccines were administered intramuscularly, in the deltoid muscle of the non-dominant upper arm.
Biological: Gardasil
2 or 3 doses of 0.5 mL supplied as a liquid in individual pre-filled syringes or vials to be administered intramuscularly in the deltoid muscle of the non-dominant arm at Day 0 and Month 6 (Gard_2D) or at Day 0, Month 2 and Month 6 (Gard_3D), respectively.

  Eligibility

Ages Eligible for Study:   9 Years to 14 Years   (Child)
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 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 14 years of age at the time of the first vaccination.
  • Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to enrolment in the study. In addition, if capable, the subject should sign and personally date a written informed assent.
  • Healthy subjects as established by medical history and clinical examination before entering into the study.
  • 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 treatment period and for two months after completion of the vaccination series.

Exclusion Criteria:

  • Pregnant or breastfeeding.
  • A woman planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the vaccination phase of the study, i.e. up to two months after the last vaccine dose.
  • Previous vaccination against HPV or planned administration of another HPV vaccine during the study other than those foreseen in the protocol.
  • Child in care.
  • 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 36).
  • 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 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 (pharmaceutical product or device).
  • Previous administration of vaccine components.
  • 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.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • 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.
  • Drug and/or alcohol abuse.
  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: NCT01462357

Locations
France
GSK Investigational Site
Dax, France, 40100
GSK Investigational Site
Draguignan, France, 83300
GSK Investigational Site
Essey les Nancy, France, 54270
GSK Investigational Site
Le Havre, France, 76620
GSK Investigational Site
Nice, France, 06300
GSK Investigational Site
Paris cedex 20, France, 75970
GSK Investigational Site
Rosiers d'Egletons, France, 19300
GSK Investigational Site
Saint Cyr Sur Loir, France, 37540
GSK Investigational Site
Seysses, France, 31600
GSK Investigational Site
Tours, France, 37100
Hong Kong
GSK Investigational Site
Pokfulam, Hong Kong
GSK Investigational Site
Shatin, Hong Kong
Singapore
GSK Investigational Site
Singapore, Singapore, 229899
GSK Investigational Site
Singapore, Singapore, 169608
GSK Investigational Site
Singapore, Singapore, 228510
GSK Investigational Site
Singapore, Singapore, 529889
GSK Investigational Site
Singapore, Singapore, 768826
GSK Investigational Site
Singapore, Singapore, 119074
Sweden
GSK Investigational Site
Eskilstuna, Sweden, SE-631 88
GSK Investigational Site
Linköping, Sweden, SE-581 85
GSK Investigational Site
Örebro, Sweden, SE-701 16
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01462357     History of Changes
Other Study ID Numbers: 115411 
Study First Received: October 27, 2011
Results First Received: August 11, 2014
Last Updated: February 25, 2016
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by GlaxoSmithKline:
Human papillomavirus
Safety
HPV vaccine
Immune response

Additional relevant MeSH terms:
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 27, 2016