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

Human Papillomavirus Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00929526
• Other study ID #: 112949
• Status: Completed
• Phase: Phase 3
• First received: June 26, 2009
• Last updated: September 13, 2012
• Start date: June 2009
• Est. completion date: February 2011

Study information

• Verified date: September 2012
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 752
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 25 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cervical Intraepithelial Neoplasia
• Human Papillomavirus Infection
• Papillomavirus Infections

Intervention

Procedure:
• Liquid-based cytology (LBC) sampling
LBC samples will be collected at Months 36 and 48 for cytology and HPV DNA testing (by PCR)
• Blood sampling
Blood samples will be collected at Months 36 and 48 for antibody determination

Locations

Country	Name	City	State
Japan	GSK Investigational Site	Aomori
Japan	GSK Investigational Site	Fukui
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Kagoshima
Japan	GSK Investigational Site	Kagoshima
Japan	GSK Investigational Site	Miyazaki
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From Month 0 up to Month 12	No
Secondary	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.	From Month 0 up to Month 12	No
Secondary	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.	From Month 0 up to Month 12	No
Secondary	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.	From Month 0 up to Month 12	No
Secondary	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.	From Month 0 up to Month 12	No
Secondary	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.	From Month 0 up to Month 12	No
Secondary	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.	From Month 0 up to Month 12	No
Secondary	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.	From Month 0 up to Month 12	No
Secondary	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.	At Month 0 and at Month 12	No
Secondary	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.	At Month 0 and at Month 12	No
Secondary	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.	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	No
Secondary	Number of Subjects With New Onset of Chronic Diseases (NOCDs) Regardless of Causal Relationship to Vaccination and Intensity.	NOCDs included autoimmune diseases, diabetes mellitus.	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	No
Secondary	Number of Subjects With New Onset of Autoimmune Diseases (NOADs) Regardless of Causal Relationship to Vaccination and Intensity.		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	No
Secondary	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.	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	No
Secondary	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).	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).	No