Extension Study of the Efficacy of the GSK 580299 Vaccine in Japanese Women Vaccinated in the Primary NCT00316693 Study

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00929526
First received: June 26, 2009
Last updated: September 13, 2012
Last verified: September 2012
  Purpose

This extension study is conducted to assess the efficacy of the GSK 580299 vaccine against cervical intraepithelial neoplasia (CIN) lesions, cervical cancer and cytological abnormalities associated with human papillomavirus (HPV)-16 and/or HPV-18 or other oncogenic HPV types for an additional two years. All subjects who participated in the primary vaccination study NCT00316693 and who confirmed their interest in participating in a long term follow up study will therefore be invited to be followed for up to 48 months after administration of the first dose of vaccine. In addition, safety and persistence of the humoral immune response will be evaluated in this study.

This protocol posting deals with objectives & outcome measures of the extension phase at Months 36 and 48. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00316693).


Condition Intervention Phase
Human Papillomavirus Infection
Procedure: Liquid-based cytology (LBC) sampling
Procedure: Blood sampling
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: Long-term Extension Study of the Efficacy of the 580299 Vaccine in the Prevention of HPV-16 and/or HPV-18 Associated Cervical Intraepithelial Neoplasia (CIN) in Japanese Women Vaccinated in the Primary Vaccination Study NCT00316693

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects Reporting Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Cases Associated With HPV16 and/or HPV18 Detected Within the Lesional Component of the Cervical Tissue Specimen. [ Time Frame: From Month 0 up to Month 12 ] [ Designated as safety issue: No ]

    Low-grade cervical lesions and higher lesions are defined as CIN1+, i.e. CIN grade 1 (CIN1), CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer (ICC).

    Detection of vaccine oncogenic Human papillomavirus (HPV) types 16 or 18 was made by polymerase chain reaction (PCR).

    For single type: Subjects Deoxyribonucleic acid (DNA) negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type.

    For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type.



Secondary Outcome Measures:
  • Number of Subjects Reporting Cytological Abnormalities and Lesions Associated With HPV-16 and/or HPV-18. [ Time Frame: From Month 0 up to Month 12 ] [ Designated as safety issue: No ]

    Cytologically confirmed abnormalities and lesions (ASC-US+) are defined as atypical squamous cell of undetermined significance (ASC-US), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), atypical squamous cell-cannot exclude HSIL (ASC-H) and atypical glandular cells (AGC).

    For single type: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type.

    For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type.


  • Number of Subjects Reporting Cytologically Confirmed Abnormalities and Lesions Concurrently Associated With Any Oncogenic HPV Types. [ Time Frame: From Month 0 up to Month 12 ] [ Designated as safety issue: No ]

    Cytologically confirmed abnormalities and lesions (ASC-US+) are defined as ASC-US, LSIL, HSIL, ASC-H and AGC.

    HR= High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.


  • Number of Subjects Reporting CIN1+ Associated With Any Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen. [ Time Frame: From Month 0 up to Month 12 ] [ Designated as safety issue: No ]

    Low-grade cervical lesions and higher lesions are defined as CIN1+, i.e. CIN1, CIN2, CIN3, AIS or ICC.

    HR=High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.


  • Number of Subjects Reporting Incident Cervical Infection Associated With HPV-16 and/or 18. [ Time Frame: From Month 0 up to Month 12 ] [ Designated as safety issue: No ]

    For single type: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type.

    For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type.


  • Number of Subjects Reporting Incident Cervical Infection With Any Oncogenic HPV Types. [ Time Frame: From Month 0 up to Month 12 ] [ Designated as safety issue: No ]
    HR=High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.

  • Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With HPV-16 and/or 18. [ Time Frame: From Month 0 up to Month 12 ] [ Designated as safety issue: No ]

    Persistent infection (12-month definition): detection of at least 2 positive HPV DNA PCR assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an approximate interval of 12 months (>300 days).

    For single type: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for the corresponding HPV type.

    For combined types: Subjects DNA negative at Month 0 and Month 6 and seronegative at Month 0 for at least one HPV type.


  • Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With Any Oncogenic HPV-types. [ Time Frame: From Month 0 up to Month 12 ] [ Designated as safety issue: No ]

    Persistent infection: subjects with at least 2 positive samples (difference > than 300 days) and no negative samples in between.

    HR=High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.


  • Number of Subjects With HPV-16 and HPV-18 Antibodies Titers Equal to or Above the Assay Cut-off Values. [ Time Frame: At Month 0 and at Month 12 ] [ Designated as safety issue: No ]
    Assay cut-off values assessed were 8 Enzyme-linked Immunosorbent Assay (ELISA) units per millilitre (EL.U/mL) for HPV-16 antibodies and 7 ELISA units per millilitre (EL.U/mL) for HPV-18 antibodies in the Cervarix Group.

  • HPV-16 and HPV-18 Antibody Titers [ Time Frame: At Month 0 and at Month 12 ] [ Designated as safety issue: No ]
    Titers were expressed as Geometric Mean Titers (GMTs). Geometric mean titres were assessed by ELISA in the Cervarix Group.

  • Number of Subjects Reporting Serious Adverse Events (SAEs). [ Time Frame: During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12 ] [ 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.

  • Number of Subjects With New Onset of Chronic Diseases (NOCDs) Regardless of Causal Relationship to Vaccination and Intensity. [ Time Frame: During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12 ] [ Designated as safety issue: No ]
    NOCDs included autoimmune diseases, diabetes mellitus.

  • Number of Subjects With New Onset of Autoimmune Diseases (NOADs) Regardless of Causal Relationship to Vaccination and Intensity. [ Time Frame: During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12 ] [ Designated as safety issue: No ]
  • Number of Subjects With Medically Significant Conditions (MSCs). [ Time Frame: During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12 ] [ Designated as safety issue: No ]
    MSCs were defined as adverse events (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 disease.

  • Number of Subjects With Pregnancies and Pregnancy Outcomes. [ Time Frame: During the follow-up period from last study visit at Month 24 in the primary vaccination study NCT00316693 until the end of this follow-up study at Month 12 (Month 48 Ext- NCT00316693). ] [ Designated as safety issue: No ]
    Pregnancy outcomes are live infant, elective termination, ectopic pregnancy, stillbirth, 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).


Enrollment: 752
Study Start Date: June 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cervarix Group
subjects received 3 doses of Cervarix™ vaccine in primary vaccination study NCT00316693.
Procedure: Liquid-based cytology (LBC) sampling
LBC samples will be collected at Months 36 and 48 for cytology and HPV DNA testing (by PCR)
Procedure: Blood sampling
Blood samples will be collected at Months 36 and 48 for antibody determination
Placebo Comparator: Aimmugen Group
subjects received 3 doses of Aimmugen ™ vaccine in primary vaccination study NCT00316693.
Procedure: Liquid-based cytology (LBC) sampling
LBC samples will be collected at Months 36 and 48 for cytology and HPV DNA testing (by PCR)

  Eligibility

Ages Eligible for Study:   20 Years to 25 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who the investigator believes that they can and will comply with the requirements of the protocol;
  • Written informed consent obtained from the subject prior to enrolment in the extension study;
  • A subject previously vaccinated in the NCT00316693 study.
  • Subjects who showed, at the last NCT00316693 study visit (at Month 24) willingness to participate in this extension study.

Exclusion Criteria:

  • Use of any HPV vaccine other than the one administered in the NCT00316693 study;
  • Use of any investigational or non-registered product other than the study vaccine since last NCT00316693 study visit, or planned use during the study period;
  • 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;
  • Subjects who were diagnosed high grade or missing cytology at Month 0 in the NCT00316693 study;
  • Pregnant females and females who were pregnant less than 3 months ago.
  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: NCT00929526

Locations
Japan
GSK Investigational Site
Aomori, Japan, 036-8003
GSK Investigational Site
Fukui, Japan, 910-0858
GSK Investigational Site
Hiroshima, Japan, 733-0813
GSK Investigational Site
Hiroshima, Japan, 734-0036
GSK Investigational Site
Kagoshima, Japan, 892-0824
GSK Investigational Site
Kagoshima, Japan, 890-0055
GSK Investigational Site
Miyazaki, Japan, 889-1692
GSK Investigational Site
Osaka, Japan, 530-0013
GSK Investigational Site
Tokyo, Japan, 183-0056
GSK Investigational Site
Tokyo, Japan, 102-0083
GSK Investigational Site
Tokyo, Japan, 173-0005
GSK Investigational Site
Tokyo, Japan, 160-0017
GSK Investigational Site
Tokyo, Japan, 189-0014
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00929526     History of Changes
Other Study ID Numbers: 112949
Study First Received: June 26, 2009
Results First Received: February 16, 2012
Last Updated: September 13, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by GlaxoSmithKline:
HPV vaccine
cervical intraepithelial neoplasia (CIN)
including new onset of autoimmune disease [NOAD])
new onset of chronic disease (NOCD)
medically significant condition (MSC)

Additional relevant MeSH terms:
Cervical Intraepithelial Neoplasia
Papillomavirus Infections
Carcinoma in Situ
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
DNA Virus Infections
Virus Diseases
Tumor Virus Infections

ClinicalTrials.gov processed this record on July 31, 2014