Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

  Show 76 Study Locations
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
Antacids
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014