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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Infections, Papillomavirus

Intervention / Treatment
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* Procedure: Liquid-based cytology (LBC) sampling
* Procedure: Blood sampling


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cervarix Group<br>subjects received 3 doses of Cervarix™ vaccine in primary vaccination study NCT00316693. | Procedure: Liquid-based cytology (LBC) sampling<br>* LBC samples will be collected at Months 36 and 48 for cytology and HPV DNA testing (by PCR)<br>Procedure: Blood sampling<br>* Blood samples will be collected at Months 36 and 48 for antibody determination<br>|
| Placebo Comparator: Aimmugen Group<br>subjects received 3 doses of Aimmugen ™ vaccine in primary vaccination study NCT00316693. | Procedure: Liquid-based cytology (LBC) sampling<br>* LBC samples will be collected at Months 36 and 48 for cytology and HPV DNA testing (by PCR)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV vaccine, cervical intraepithelial neoplasia (CIN), including new onset of autoimmune disease [NOAD]), new onset of chronic disease (NOCD), medically significant condition (MSC)