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

Primary Purpose

Infections, Papillomavirus

Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Liquid-based cytology (LBC) sampling
Blood sampling
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Infections, Papillomavirus focused on measuring HPV vaccine, cervical intraepithelial neoplasia (CIN), including new onset of autoimmune disease [NOAD]), new onset of chronic disease (NOCD), medically significant condition (MSC)

Eligibility Criteria

20 Years - 25 Years (Adult)FemaleAccepts Healthy Volunteers

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.

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cervarix Group

Aimmugen Group

Arm Description

subjects received 3 doses of Cervarix™ vaccine in primary vaccination study NCT00316693.

subjects received 3 doses of Aimmugen ™ vaccine in primary vaccination study NCT00316693.

Outcomes

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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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).
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.
NOCDs included autoimmune diseases, diabetes mellitus.
Number of Subjects With New Onset of Autoimmune Diseases (NOADs) Regardless of Causal Relationship to Vaccination and Intensity.
Number of Subjects With Medically Significant Conditions (MSCs).
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.
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).

Full Information

First Posted
June 26, 2009
Last Updated
September 9, 2016
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT00929526
Brief Title
Extension Study of the Efficacy of the GSK 580299 Vaccine in Japanese Women Vaccinated in the Primary NCT00316693 Study
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
June 2009 (undefined)
Primary Completion Date
February 2011 (Actual)
Study Completion Date
February 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infections, Papillomavirus
Keywords
HPV vaccine, cervical intraepithelial neoplasia (CIN), including new onset of autoimmune disease [NOAD]), new onset of chronic disease (NOCD), medically significant condition (MSC)

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
752 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cervarix Group
Arm Type
Experimental
Arm Description
subjects received 3 doses of Cervarix™ vaccine in primary vaccination study NCT00316693.
Arm Title
Aimmugen Group
Arm Type
Placebo Comparator
Arm Description
subjects received 3 doses of Aimmugen ™ vaccine in primary vaccination study NCT00316693.
Intervention Type
Procedure
Intervention Name(s)
Liquid-based cytology (LBC) sampling
Intervention Description
LBC samples will be collected at Months 36 and 48 for cytology and HPV DNA testing (by PCR)
Intervention Type
Procedure
Intervention Name(s)
Blood sampling
Intervention Description
Blood samples will be collected at Months 36 and 48 for antibody determination
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
From Month 0 up to Month 12
Secondary Outcome Measure Information:
Title
Number of Subjects Reporting Cytological Abnormalities and Lesions Associated With HPV-16 and/or HPV-18.
Description
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.
Time Frame
From Month 0 up to Month 12
Title
Number of Subjects Reporting Cytologically Confirmed Abnormalities and Lesions Concurrently Associated With Any Oncogenic HPV Types.
Description
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.
Time Frame
From Month 0 up to Month 12
Title
Number of Subjects Reporting CIN1+ Associated With Any Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen.
Description
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.
Time Frame
From Month 0 up to Month 12
Title
Number of Subjects Reporting Incident Cervical Infection Associated With HPV-16 and/or 18.
Description
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.
Time Frame
From Month 0 up to Month 12
Title
Number of Subjects Reporting Incident Cervical Infection With Any Oncogenic HPV Types.
Description
HR=High-risk HPV-types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Time Frame
From Month 0 up to Month 12
Title
Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With HPV-16 and/or 18.
Description
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.
Time Frame
From Month 0 up to Month 12
Title
Number of Subjects Reporting Persistent Long-term Cervical Infection (12-month Definition) With Any Oncogenic HPV-types.
Description
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.
Time Frame
From Month 0 up to Month 12
Title
Number of Subjects With HPV-16 and HPV-18 Antibodies Titers Equal to or Above the Assay Cut-off Values.
Description
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.
Time Frame
At Month 0 and at Month 12
Title
HPV-16 and HPV-18 Antibody Titers
Description
Titers were expressed as Geometric Mean Titers (GMTs). Geometric mean titres were assessed by ELISA in the Cervarix Group.
Time Frame
At Month 0 and at Month 12
Title
Number of Subjects Reporting Serious Adverse Events (SAEs).
Description
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.
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
Title
Number of Subjects With New Onset of Chronic Diseases (NOCDs) Regardless of Causal Relationship to Vaccination and Intensity.
Description
NOCDs included autoimmune diseases, diabetes mellitus.
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
Title
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
Title
Number of Subjects With Medically Significant Conditions (MSCs).
Description
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.
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
Title
Number of Subjects With Pregnancies and Pregnancy Outcomes.
Description
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).
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).

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Aomori
ZIP/Postal Code
036-8003
Country
Japan
Facility Name
GSK Investigational Site
City
Fukui
ZIP/Postal Code
910-0858
Country
Japan
Facility Name
GSK Investigational Site
City
Hiroshima
ZIP/Postal Code
733-0813
Country
Japan
Facility Name
GSK Investigational Site
City
Hiroshima
ZIP/Postal Code
734-0036
Country
Japan
Facility Name
GSK Investigational Site
City
Kagoshima
ZIP/Postal Code
890-0055
Country
Japan
Facility Name
GSK Investigational Site
City
Kagoshima
ZIP/Postal Code
892-0824
Country
Japan
Facility Name
GSK Investigational Site
City
Miyazaki
ZIP/Postal Code
889-1692
Country
Japan
Facility Name
GSK Investigational Site
City
Osaka
ZIP/Postal Code
530-0013
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
102-0083
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
160-0017
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
173-0005
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
183-0056
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
189-0014
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Citations:
PubMed Identifier
31824976
Citation
Chen J, Gopala K, Akarsh PK, Struyf F, Rosillon D. Prevalence and Incidence of Human Papillomavirus (HPV) Infection Before and After Pregnancy: Pooled Analysis of the Control Arms of Efficacy Trials of HPV-16/18 AS04-Adjuvanted Vaccine. Open Forum Infect Dis. 2019 Dec 4;6(12):ofz486. doi: 10.1093/ofid/ofz486. eCollection 2019 Dec. Erratum In: Open Forum Infect Dis. 2020 Feb 28;7(3):ofaa036.
Results Reference
derived
PubMed Identifier
25424783
Citation
Konno R, Yoshikawa H, Okutani M, Quint W, V Suryakiran P, Lin L, Struyf F. Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical intraepithelial neoplasia and cervical infection in young Japanese women. Hum Vaccin Immunother. 2014;10(7):1781-94. doi: 10.4161/hv.28712.
Results Reference
derived
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112949
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112949
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112949
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112949
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112949
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
112949
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register

Learn more about this trial

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

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