Study to Evaluate the Efficacy of the Human Papillomavirus Vaccine in Healthy Adult Women of 26 Years of Age and Older

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00294047
First received: February 17, 2006
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

This is a multicentre study in which women were planned to receive either the Human Papillomavirus Vaccine (HPV) vaccine or control. Under Protocol Amendment 3, study participation will last approximately 48 months and involves a total of eleven scheduled visits. Under Protocol Amendment 4, study participation will last up to 84 months and involves a maximum of seventeen scheduled visits.


Condition Intervention Phase
Infections, Papillomavirus
Biological: Cervarix
Biological: Placebo control
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Study to Evaluate Safety, Immunogenicity and Efficacy of GSK Biologicals HPV-16/18 L1/AS04 Vaccine Administered Intramuscularly According to a Three-dose Schedule (0, 1, 6 Month) in Healthy Adult Female Subjects Aged 26 Years and Above

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection. [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    CIN1+ = CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.

    Persistent HPV infection = detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.

    • DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and 6 and seronegative/positive (sero-/+) at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA)
    • Overall: subjects DNA- at Month 0 and 6 for the corresponding HPV-type, regardless of initial serostatus

  • Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 and/or With Histopathologically-CIN1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the HPV Type Assignment Algorithm (TAA). [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    CIN1+ = CIN grades 1, 2 and 3, AIS and invasive cervical cancer. Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.

    • DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0).
    • Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.


Secondary Outcome Measures:
  • Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.

    Detection was done in:

    • DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0).
    • Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

  • Number of Subjects With Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    Persistent cervical HPV infection (12-month definition) was defined as the detection of the same HPV type(s) PCR in cervical samples at all available time points over approximately a 12-month interval (evaluations are planned at approximately 6-month intervals).

    • DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0).
    • Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

  • Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types Individually or in Combinations. [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.

    Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

    Detection was done in subjects HPV DNA- for the corresponding HPV type at baseline (at month 0 and Month 6) regardless of initial serostatus.

    HPV-HRW=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18. HPV-HR=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.


  • Number of Subjects With Persistent Infection (12-month Definition) With Oncogenic HPV Types Individually or in Combinations. [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    Persistent HPV infection (12-month definition) = detection of the same HPV type(s) by PCR in cervical samples at available time points over approximately a 12-month interval (evaluations are planned at approximately 6-month intervals).

    Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

    subjects HPV DNA- for the corresponding HPV type at Month 0 6, regardless of initial serostatus.

    HPV-HRW=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HPV-HR=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 , 68


  • Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    CIN2+ was defined as CIN grades 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.

    Detection was done in:

    • DNA- and sero-: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0).
    • Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

    Note: Results for seropositive status were not analysed.


  • Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.

    Detection was done in:

    • DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0).
    • Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

  • Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Within the Lesional Component of the Cervical Tissue Specimen [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.

    Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus.


  • Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Irrespective of HPV Cervical Infection and Irrespective of Baseline HPV DNA Status [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.

    Detection was done on all subjects irrespective of their baseline HPV DNA status.


  • Number of Subjects With Any Cytological Abnormalities Associated With HPV-16 or HPV-18 Cervical Infection [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-US).

    Detection was done in:

    • DNA- and sero-: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Month 0).
    • Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

    Results for seropositive status were not analysed.


  • Number of Subjects With Cytological Abnormalities Associated With Oncogenic HPV Types Individually or in Combinations [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

    Detection was done in subjects who were HPV DNA negative for the corresponding HPV type at baseline (at month 0 and Month 6) regardless of initial serostatus.

    HRW-HPV= All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HPV-HR= High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68


  • Number of Subjects With Histopathologically Confirmed Reduction of Local Cervical Therapy [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]
    Detection was done on all subjects irrespective of their baseline HPV DNA status.

  • Number of Subjects With First Colposcopy [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]
    Detection was done on all subjects irrespective of their baseline HPV DNA status.

  • Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.

    CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.

    Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus.


  • Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 and/or With Histopathologically-confirmed CIN1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the HPV Type Assignment Algorithm (TAA). [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.

    Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus.

    The lesion was assigned to an HPV type found in the lesion if (1) the same HPV type was found in at least 1 of the 2 (closest) preceding cytology samples, or (2) none of the HPV types found in the lesion were found in any of the 2 preceding cytology samples (isolate HPV types)


  • Number of Seroconverted Subjects Against HPV-16 in the Immunogenicity Subset. [ Time Frame: At pre-vaccination and at Month 7, 12, 18, 24, 36 and 48 ] [ Designated as safety issue: No ]

    Seroconversion was defined as the appearance of antibodies (i.e.; titre greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.

    HPV-16 assay cut-off value was defined as greater than or equal to 8 ELISA units per millilitre (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 8 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 8 EL.U/mL prior to vaccination.

    Immuno subset=subjects from selected sites N≥1000, at least 250 per region


  • Number of Seroconverted Subjects Against HPV-18 in the Immunogenicity Subset. [ Time Frame: At pre-vaccination and at Month 7, 12, 18, 24, 36 and 48 ] [ Designated as safety issue: No ]

    Seroconversion was defined as the appearance of antibodies (i.e.; titre greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.

    HPV-18 assay cut-off value was defined as greater than or equal to 7 ELISA units per millilitre (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 7 EL.U/mL prior to vaccination.

    Immuno subset=subjects from selected sites N≥1000, at least 250 per region


  • Number of Seroconverted Subjects Against HPV-16 and HPV-18 in the Immunogenicity Subset. [ Time Frame: At Month 60, 72 and 84 ] [ Designated as safety issue: No ]

    Results are not yet available. It will be updated when additional data become available.

    Immuno subset=subjects came from selected sites (N≥1000, at least 250 per region)


  • Geometric Mean Concentrations (GMCs) Against HPV-16 Antibody in the Immunogenicity Subset. [ Time Frame: At pre-vaccination and at Month 7, 12, 18, 24, 36 and 48 ] [ Designated as safety issue: No ]

    GMCs were expressed in ELISA units per milliliter (EL.U/mL).

    Seronegative (Sero-) subjects are subjects who had an antibody concentration below 8 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 8 EL.U/mL prior to vaccination.

    Immuno subset=subjects from selected sites (N≥1000, at least 250 per region)


  • Geometric Mean Concentrations (GMCs) Against HPV-18 Antibody in the Immunogenicity Subset. [ Time Frame: At pre-vaccination and at Month 7, 12, 18, 24, 36 and 48 ] [ Designated as safety issue: No ]

    GMCs were expressed in ELISA units per milliliter (EL.U/mL).

    Seronegative (Sero-) subjects are subjects who had an antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 7 EL.U/mL prior to vaccination.

    Immuno subset=subjects from selected sites (N≥1000, at least 250 per region)


  • Geometric Mean Concentrations (GMCs) Against HPV-16 and HPV-18 Antibodies in the Immunogenicity Subset. [ Time Frame: At Month 60, 72 and 84 ] [ Designated as safety issue: No ]

    Results are not yet available. It will be updated when additional data become available.

    Immuno subset=subjects came from selected sites (N≥1000, at least 250 per region)


  • Number of Seroconverted Subjects Against HPV-16 and HPV-18 Viral Neutralization in a Selected Subset of Subjects. [ Time Frame: Prior to vaccination and at Month 7, 12, 18, 24 and 48. ] [ Designated as safety issue: No ]

    Seroconversion was defined as the appearance of antibodies (i.e.; titre greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.

    HPV-16/18 assay cut-off value was defined as greater than or equal to 40 Estimated dose 50% (ED50). Sero- subjects are subjects who had an antibody concentration below 40 ED50 prior to vaccination. Sero+ subjects are subjects who had an antibody concentration equal to or above 50 ED50 prior to vaccination.

    ED50 = the estimated serum dilution reducing the signal generated by viral infection by 50%


  • Geometric Mean Titers (GMTs) Against HPV-16 and HPV-18 Viral Neutralization Antibodies in a Selected Subset of Subjects. [ Time Frame: Prior to vaccination and at Month 7, 12, 18, 24 and 48. ] [ Designated as safety issue: No ]

    Titers are expressed as geometric mean antibody titers (GMTs).

    Seronegative (Sero-) subjects are subjects who had an antibody titer below 40 ED50 prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody titer equal to or above 40 ED50 prior to vaccination.

    ED50 = Estimated dose 50%, the estimated serum dilution reducing the signal generated by viral infection by 50%


  • Number of Seroconverted Subjects Against HPV-16/18 in Vaccine Recipients With Breakthrough HPV-16 and/or HPV-18 Persistent Infections and HPV-16 and/or HPV-18 Associated CIN1+ Lesions. [ Time Frame: Up to Month 84 ] [ Designated as safety issue: No ]
    This outcome will be updated once results become available. Only seronegative subjects for the corresponding HPV type prior to vaccination were analysed.

  • GMTs Against HPV-16/18 Antibodies in Vaccine Recipients With Breakthrough HPV-16 and/or HPV-18 Persistent Infections and HPV-16 and/or HPV-18 Associated CIN1+ Lesions. [ Time Frame: Up to Month 84 ] [ Designated as safety issue: No ]
    This outcome will be updated once results become available. Only seronegative subjects for the corresponding HPV type prior to vaccination were analysed.

  • Number of Seroconverted Subjects Against HPV-16 and HPV-18 (V5/J4 Monoclonal Inhibition Test). [ Time Frame: Up to Month 84 ] [ Designated as safety issue: No ]
    This outcome will be updated once results become available. Only seronegative subjects for the corresponding HPV type prior to vaccination were analysed.

  • HPV-16 and HPV-18 Geometric Mean Titers (GMTs) (V5/J4 Monoclonal Inhibition Test). [ Time Frame: Up to Month 84 ] [ Designated as safety issue: No ]
    This outcome will be updated once results become available. Only seronegative subjects for the corresponding HPV type prior to vaccination were analysed.

  • Number of Seroconverted Subjects Against HPV-16 and HPV-18 Viral Neutralization. [ Time Frame: Up to Month 84 ] [ Designated as safety issue: No ]
    This outcome will be updated once results become available. Only seronegative subjects for the corresponding HPV type prior to vaccination were analysed.

  • Geometric Mean Titers (GMTs) Against HPV-16 and HPV-18 Viral Neutralization Antibodies. [ Time Frame: Up to Month 84 ] [ Designated as safety issue: No ]
    This outcome will be updated once results become available. Only seronegative subjects for the corresponding HPV type prior to vaccination were analysed.

  • Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms. [ Time Frame: Within 7 days (Days 0-6) after vaccination ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal activity. Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).

  • Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. [ Time Frame: Within 7 days (Days 0-6) after vaccination ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and fever (Fever = axillary temperature above 37.5 degrees Celsius (°C)). Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 urticaria = urticaria distributed on at least 4 body areas. Grade 3 fever = axillary temperature above 39.0°C.

  • Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs). [ Time Frame: Within 30 days (Days 0 - 29) post-vaccination period. ] [ Designated as safety issue: No ]

    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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 unsolicited AE = an event that prevented normal activity.

    A related AE = event assessed by the investigator as causally related to the study vaccination.


  • Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs). [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. A related SAE was defined as an event assessed by the investigator as causally related to the study vaccination.

  • Number of Subjects Reporting Related or Fatal Serious Adverse Event. [ Time Frame: Up to Month 84 ] [ Designated as safety issue: No ]
  • Number of Subjects Reporting Any AE/SAE Leading to Premature Discontinuation of the Study. [ Time Frame: Up to Month 84 ] [ Designated as safety issue: No ]
  • Number of Subjects Reporting New Onset of Chronic Disease (NOCDs). [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]
    NOCDs include autoimmune disorders, asthma and type I diabetes.

  • Number of Subjects Reporting New Onset of Autoimmune Disease (NOADs). [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]
  • Number of Subjects Reporting Medically Significant Conditions (MAEs). [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]
    Medically significant conditions were defined as: AEs prompting emergency room or physician visits that were not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that were not related to common diseases. Common diseases included: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.

  • Number of Subjects With Pregnancies and Their Outcomes. [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]
    Pregnancy outcomes are live infant, premature live infant, elective termination, ectopic pregnancy, spontaneous abortion, lost to follow-up and pregnancy ongoing. For each category it was specified if the infant presents congenital anomaly (CA) or no apparent congenital anomaly (No ACA).

  • Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the Type Assignment Algorithm (TAA) [ Time Frame: Up to Month 48 ] [ Designated as safety issue: No ]

    CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.

    Detection was done on subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.

    TAA: Type assignment algorithm. The lesion was assigned to an HPV type found in the lesion if

    1. the same HPV type was found in at least one of the two (closest) preceding cytology samples, or
    2. none of the HPV types found in the lesion were found in any of the two preceding cytology samples (isolate HPV types)


Enrollment: 5752
Study Start Date: February 2006
Study Completion Date: January 2014
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cervarix Group
Subjects received 3 doses of Cervarix™ vaccine. Cervarix vaccine was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.
Biological: Cervarix
Subjects were planned to receive three doses of the study vaccine administered intramuscularly according to a 0, 1, 6 month vaccination schedule.
Placebo Comparator: Aluminium Hydroxide Group
Subjects received 3 doses of Aluminium Hydroxide [Al(OH)3]. Aluminium Hydroxide was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.
Biological: Placebo control
Subjects were planned to receive three doses of the control vaccine administered intramuscularly according to a 0, 1, 6 month vaccination schedule.

Detailed Description:

The Protocol Posting has been updated due to protocol amendment 5 and in order to comply with the FDA Amendment Act, Sep 2007.

  Eligibility

Ages Eligible for Study:   26 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

  • A woman who the investigator believes that she can and will comply with the requirements of the protocol.
  • A women of at least 26 years of age at the time of the first vaccination.
  • Written informed consent obtained from the subject prior to enrolment.
  • Free of obvious health problems as established by medical history and clinical examination before entering into the study.
  • Subject must have intact cervix.
  • Subject must have a negative urine pregnancy test. This test is not applicable to women of non-childbearing potential.
  • Subject must be of non-childbearing potential or, if of childbearing potential, she must be abstinent or must be using an effective method of birth control for 30 days prior to the first vaccination and must agree to continue such precautions for two months after completion of the vaccination series.

Exclusion criteria:

  • Pregnant or breastfeeding (women must be at least three months post-pregnancy and not breastfeeding to enter the study).
  • A women 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 (Month 0 - 8).
  • 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 84).
  • 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 (i.e. days 0 - 29) the first dose of study vaccine. Planned administration/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.
  • Previous administration of components of the investigational vaccine
  • Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period.
  • History of HPV infection/treatment or planned treatment to evaluate an abnormal cervical cytology (Pap smear) test, e.g. colposcopy.
  • Any medically diagnosed or suspected 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 vaccine.
  • Hypersensitivity to latex.
  • Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests.
  • History of chronic condition(s) requiring treatment.
  • Administration of immunoglobulins and/or any blood product within three months preceding the first dose of study vaccine, or planned administration during the study period. Enrolment will be deferred until the subject is outside of specified window.
  • Acute disease at the time of enrolment.
  • Heavy bleeding (menstruation or other) or heavy vaginal discharge in which a pelvic exam cannot be performed (and no cervical sample can be taken). Enrolment will be deferred until condition is resolved according to investigators medical judgement.
  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: NCT00294047

  Hide Study Locations
Locations
United States, California
GSK Investigational Site
Fountain Valley, California, United States, 92708
United States, Colorado
GSK Investigational Site
Aurora, Colorado, United States, 80045
GSK Investigational Site
Golden, Colorado, United States, 80401
United States, Florida
GSK Investigational Site
Coral Gables, Florida, United States, 33134
GSK Investigational Site
Miami, Florida, United States, 33136
United States, Georgia
GSK Investigational Site
Augusta, Georgia, United States, 30912
United States, Iowa
GSK Investigational Site
Iowa City, Iowa, United States, 52242
United States, Kansas
GSK Investigational Site
Wichita, Kansas, United States, 67207
United States, Kentucky
GSK Investigational Site
Bardstown, Kentucky, United States, 40004
GSK Investigational Site
Louisville, Kentucky, United States, 40202
United States, Minnesota
GSK Investigational Site
Chaska, Minnesota, United States, 55318
United States, Nebraska
GSK Investigational Site
Omaha, Nebraska, United States, 68131
United States, New Hampshire
GSK Investigational Site
Lebanon, New Hampshire, United States, 03756
United States, New Mexico
GSK Investigational Site
Albuquerque, New Mexico, United States, 87131
United States, New York
GSK Investigational Site
Syracuse, New York, United States, 13057
United States, North Carolina
GSK Investigational Site
Chapel Hill, North Carolina, United States, 27514
GSK Investigational Site
New Bern, North Carolina, United States, 28562
United States, Ohio
GSK Investigational Site
Akron, Ohio, United States, 44311
GSK Investigational Site
Cleveland, Ohio, United States, 44122
United States, Oklahoma
GSK Investigational Site
Tulsa, Oklahoma, United States, 74105
United States, Oregon
GSK Investigational Site
Portland, Oregon, United States, 97210
United States, Pennsylvania
GSK Investigational Site
Carnegie, Pennsylvania, United States, 15106
GSK Investigational Site
Erie, Pennsylvania, United States, 16508
GSK Investigational Site
Erie, Pennsylvania, United States, 16507
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19107
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15213
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15236
GSK Investigational Site
Wexford, Pennsylvania, United States, 15090
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78705
GSK Investigational Site
Houston, Texas, United States, 77030
GSK Investigational Site
Houston, Texas, United States, 77004
United States, Utah
GSK Investigational Site
Salt Lake City, Utah, United States, 84109
GSK Investigational Site
Salt Lake City, Utah, United States, 84121
GSK Investigational Site
South Jordan, Utah, United States, 84095
United States, Washington
GSK Investigational Site
Wenatchee, Washington, United States, 98801
United States, Wisconsin
GSK Investigational Site
La Crosse, Wisconsin, United States, 54601
Australia, Tasmania
GSK Investigational Site
Hobart, Tasmania, Australia
Australia, Victoria
GSK Investigational Site
Parkville, Victoria, Australia, 3052
Australia, Western Australia
GSK Investigational Site
Perth, Western Australia, Australia
Canada, Alberta
GSK Investigational Site
Edmonton, Alberta, Canada, T6G 2C8
Canada, British Columbia
GSK Investigational Site
Vancouver, British Columbia, Canada, V6H 3N1
Canada, Nova Scotia
GSK Investigational Site
Halifax, Nova Scotia, Canada, B3H 2Y9
GSK Investigational Site
Truro, Nova Scotia, Canada, B2N 1L2
Canada, Ontario
GSK Investigational Site
Waterloo, Ontario, Canada, N2L 6H6
Canada, Quebec
GSK Investigational Site
Sherbrooke, Quebec, Canada, J1H 1Z1
Canada
GSK Investigational Site
Quebec, Canada, G1S 2L6
Mexico
GSK Investigational Site
Cuenavaca, Morelos, Mexico, 62430
GSK Investigational Site
Jojutla / Morelos, Mexico
Netherlands
GSK Investigational Site
Amsterdam, Netherlands, 1007 MB
GSK Investigational Site
Delft, Netherlands, 2625 AD
GSK Investigational Site
Rotterdam, Netherlands, 3015 CE
Peru
GSK Investigational Site
Lima, Peru
Philippines
GSK Investigational Site
Laguna, Philippines
GSK Investigational Site
San Pablo City, Philippines
GSK Investigational Site
Taft Avenue, Manila, Philippines, 1700
Portugal
GSK Investigational Site
Almada, Portugal, 2805-267 Almada
GSK Investigational Site
Coimbra, Portugal, 3000-075 Coimbra
GSK Investigational Site
Lisboa, Portugal, 1200-831 Lisboa
GSK Investigational Site
Porto, Portugal, 4200-023 Porto
GSK Investigational Site
Setúbal, Portugal, 2910-446 Setúbal
Russian Federation
GSK Investigational Site
Ekaterinburg, Russian Federation, 620073
GSK Investigational Site
Moscow, Russian Federation, 115 478
GSK Investigational Site
Moscow, Russian Federation, 109263
GSK Investigational Site
Moscow, Russian Federation, 117997
GSK Investigational Site
Sankt-Petersburg, Russian Federation, 190020
GSK Investigational Site
Sankt-Petersburg, Russian Federation, 199034
Singapore
GSK Investigational Site
Singapore, Singapore, 229899
GSK Investigational Site
Singapore, Singapore, 119074
Thailand
GSK Investigational Site
Bangkok, Thailand, 10700
GSK Investigational Site
Bangkok, Thailand, 10400
United Kingdom
GSK Investigational Site
Northwood, Middlesex, United Kingdom, HA6 2RN
GSK Investigational Site
Aberdeen, United Kingdom, AB25 7ZD
GSK Investigational Site
Cardiff, United Kingdom, CF14 4XN
GSK Investigational Site
Gateshead, United Kingdom, NE9 6SX
GSK Investigational Site
London, United Kingdom, EC1M 6BQ
GSK Investigational Site
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Skinner R et al. HPV-16/18 AS04-Adjuvanted vaccine efficacy in ≥26-year-old women after 4-year follow-up. Abstract presented in the 27th International Papillomavirus Conference and Clinical Workshop (IPV). Berlin, Germany, 17-22 September 2011.
Descamps D et al. (2009) Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: A pooled analysis of 11 clinical trials. Hum Vaccin. 5(5):51-59.
Skinner R et al. Effect of HPV type on risk of progression from HPV infection to CIN1+ and CIN2+ in women aged 26 years and over. Abstract presented at the 28th International Papillomavirus Conference and Clinical Workshop (IPC & CW), San Juan, Puerto Rico, 30 Nov - 06 Dec 2012.

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00294047     History of Changes
Other Study ID Numbers: 104820
Study First Received: February 17, 2006
Results First Received: December 8, 2011
Last Updated: March 27, 2014
Health Authority: Peru: Instituto Nacional de Salud
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Portugal: Infarmed - Autoridade Nacional do Medicamento e Produtos de Saúde, I.P.
Mexico: Ministry of Health - Secretaria de Salud - Comisión de Autorización Sanitaria - Comisión Federal para la Protección cotnra riesgos de salud
Russian Federation: Federal service on surveillance in healthcare and social development of Russian Federation
Singapore: Health Sciences Authority
Canada: Biologics and Genetics Therapeutic Directorate (B>D)
Thailand: The Ethical Review Committee for Research in Human Subjects, Ministry of Public health
Philippines: Bureau of Food and Drugs
United States: Food and Drug Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Australia: Therapeutic Goods Administration

Keywords provided by GlaxoSmithKline:
Vaccine
Human papillomavirus
Cervical Cancer
Cervical Infection

Additional relevant MeSH terms:
Infection
Aluminum Hydroxide
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014