A Double-Blind, Controlled, Randomized, Phase III Study of the Efficacy of an HPV16/18 VLP Vaccine in the Prevention of Advanced Cervical Intraepithelial Neoplasia (CIN2, CIN3, Adenocarcinoma In Situ [AIS] and Invasive Cervical Cancer) Associated With HPV 16 or HPV 18 Cervical Infection in Healthy Young Adult Women in Costa Rica.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 7,466
- 试验地点
- 1
- 主要终点
- Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.
研究概览
简要总结
RATIONALE: Chemoprevention is the use of certain drugs to keep cancer form forming, growing, or coming back. Vaccines may help the body build an effective immune response against human papillomavirus and may be effective in preventing cervical intraepithelial neoplasia or cervical cancer. It is not yet known whether human papillomavirus vaccine is more effective than hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer.
PURPOSE: This randomized phase III trial is studying human papillomavirus vaccine to see how well it works compared to hepatitis A vaccine in preventing cervical intraepithelial neoplasia or cervical cancer in younger healthy participants.
详细描述
OBJECTIVES:
Primary
•Demonstrate the efficacy of the candidate vaccine, human papillomavirus 16/18 (HPV 16/18) L1 virus-like particle (VLP)/AS04 vaccine compared with control in preventing grade 2 or 3 cervical intraepithelial neoplasia, adenocarcinoma in situ of the cervix, or invasive cervical cancer (CIN2+) associated with HPV 16 or HPV 18 cervical infection in younger healthy participants who are negative for HPV DNA by polymerase chain reaction (PCR) for the corresponding HPV type at months 0 and 6.
Secondary
- Determine the duration of protection against HPV 16 or HPV 18 cervical infection in participants treated with the HPV 16/18 L1 VLP/AS04 vaccine.
- Determine the safety of this vaccine in these participants, regardless of their initial HPV 16/18 DNA status.
- Evaluate the efficacy of the candidate vaccine, HPV 16/18 L1 VLP/AS04 vaccine compared with control in preventing CIN2+ associated with any oncogenic HPV type cervical infection in participants who are negative for HPV DNA by PCR for the corresponding HPV type at months 0 and 6.
- Compare the efficacy of the candidate vaccine with control in preventing CIN2+ associated with HPV 16 or HPV 18 cervical infection, detected within the lesional component of the cervical tissue specimen by PCR, in participants who are negative for HPV DNA by PCR for the corresponding HPV type at months 0 and 6 and by enzyme-linked immunosorbent assay (ELISA) at month 0.
- Compare the efficacy of the candidate vaccine with control in preventing persistent HPV 16 or HPV 18 cervical infection in these participants.
- Determine the immunogenicity of HPV 16/18 L1 VLP/AS04 vaccine by ELISA and V5/J4 monoclonal antibody inhibition enzyme immunoassay in the first 600 participants randomized to receive HPV 16/18 L1 VLP/AS04 vaccine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 25 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cervarix Group
Subjects received 3 doses of Cervarix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
干预措施: human papillomavirus 16/18 L1 virus-like particle/AS04 vaccine (Biological)
Havrix Group
Subjects received 3 doses of Havrix vaccine at study Months 0, 1 and 6. All the vaccine doses were administered intramuscularly in the deltoid region of the non-dominant arm.
干预措施: hepatitis A inactivated virus vaccine (Biological)
结局指标
主要结局
Number of Histopathologically Confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Cases Associated With HPV16 and/or HPV18 Infection Detected in the Preceding Cervical Cytology Specimen.
时间窗: From Month 6 up to Month 48
CIN2+ was defined as CIN grade 2 (CIN2), CIN grade 3 (CIN3), adenocarcinoma in situ (AIS) or invasive cervical cancer. Preceding cervical cytology means the last cervical cytology specimen collected before the histopathology specimen was obtained. Subjects were human papillomavirus (HPV) deoxyribonucleic acid (DNA) negative (DNA-) by polymerase chain reaction (PCR) at Month 0 and Month 6 for the corresponding HPV-type.
次要结局
- Number of Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 Cases(From Month 6 up to Month 48)
- Number of Cervical Infection With HPV16 or HPV18.(From the fourth year follow-up period)
- Number of Histopathologically Confirmed CIN2+ Cases Associated With Infection by Any Oncogenic HPV Type(From Month 6 up to Month 48)
- Geometric Mean Titers (GMTs) for HPV-16 Antibody in the Immunogenicity Subcohort.(Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48)
- Geometric Mean Titers (GMTs) for HPV-18 Antibody in the Immunogenicity Subcohort(Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48)
- HPV-16 Geometric Mean Titers (GMTs) (V5 Monoclonal Antibody Inhibition Test)(Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48)
- HPV-18 Geometric Mean Titers (GMTs) (J4 Monoclonal Antibody Inhibition Test)(Before vaccination and at Month 1, 6, 7, 12, 18, 24, 30, 36, 42 and 48)
- Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms.(Within 60 minutes after vaccination)
- Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms on a 10% Random Subset of Participants.(From Day 3 to Day 6 after vaccination)
- Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.(Within 60 minutes after vaccination)
- Number of Subjects Reporting Any and Grade 3 Solicited General Symptoms on a 10% Random Subset of Participants.(From Day 3 to Day 6 after vaccination)
- Number of Subjects Reporting Serious Adverse Events (SAEs).(During the entire study period (From Month 0 up to Month 48).)
- Number of Subjects Reporting Unsolicited Adverse Events (AEs).(within 30 days (Days 0-29) after vaccination)
- Number of Subjects With All Possible Pregnancy Outcomes(During the entire study period (From Month 0 up to Month 48).)