A Study to Evaluate Safety, Immunogenicity and Efficacy of GSK Biologicals HPV-16/18 L1/AS04 Vaccine Administered Intramuscularly According to a Three-dose Schedule (0, 1, 6 Month) in Healthy Adult Female Subjects Aged 26 Years and Above
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 5,752
- 试验地点
- 75
- 主要终点
- Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 and/or With Histopathologically-CIN1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the HPV Type Assignment Algorithm (TAA).
研究概览
简要总结
This is a multicentre study in which women were planned to receive either the Human Papillomavirus Vaccine (HPV) vaccine or control. Under Protocol Amendment 3, study participation will last approximately 48 months and involves a total of eleven scheduled visits. Under Protocol Amendment 4, study participation will last up to 84 months and involves a maximum of seventeen scheduled visits.
详细描述
The Protocol Posting has been updated due to protocol amendment 5 and in order to comply with the FDA Amendment Act, Sep 2007.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 26 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •A woman who the investigator believes that she can and will comply with the requirements of the protocol.
- •A women of at least 26 years of age at the time of the first vaccination.
- •Written informed consent obtained from the subject prior to enrolment.
- •Free of obvious health problems as established by medical history and clinical examination before entering into the study.
- •Subject must have intact cervix.
- •Subject must have a negative urine pregnancy test. This test is not applicable to women of non-childbearing potential.
- •Subject must be of non-childbearing potential or, if of childbearing potential, she must be abstinent or must be using an effective method of birth control for 30 days prior to the first vaccination and must agree to continue such precautions for two months after completion of the vaccination series.
排除标准
- •Pregnant or breastfeeding (women must be at least three months post-pregnancy and not breastfeeding to enter the study).
- •A women planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the vaccination phase of the study, i.e. up to two months after the last vaccine dose (Month 0 - 8).
- •Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 84).
- •Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
- •Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after (i.e. days 0 - 29) the first dose of study vaccine. Planned administration/administration of routine vaccines up to 8 days before the first dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window.
- •Previous administration of components of the investigational vaccine
- •Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period.
- •History of HPV infection/treatment or planned treatment to evaluate an abnormal cervical cytology (Pap smear) test, e.g. colposcopy.
- •Any medically diagnosed or suspected immunodeficient condition based on medical history and physical examination.
- •History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccine.
- •Hypersensitivity to latex.
- •Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests.
- •History of chronic condition(s) requiring treatment.
- •Administration of immunoglobulins and/or any blood product within three months preceding the first dose of study vaccine, or planned administration during the study period. Enrolment will be deferred until the subject is outside of specified window.
- •Acute disease at the time of enrolment.
- •Heavy bleeding (menstruation or other) or heavy vaginal discharge in which a pelvic exam cannot be performed (and no cervical sample can be taken). Enrolment will be deferred until condition is resolved according to investigators medical judgement.
研究组 & 干预措施
Aluminium Hydroxide Group
Subjects received 3 doses of Aluminium Hydroxide [Al(OH)3]. Aluminium Hydroxide was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.
干预措施: Placebo control (Biological)
Cervarix Group
Subjects received 3 doses of Cervarix™ vaccine. Cervarix vaccine was administered intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.
干预措施: Cervarix (Biological)
结局指标
主要结局
Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 and/or With Histopathologically-CIN1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the HPV Type Assignment Algorithm (TAA).
时间窗: Up to Month 84
CIN1+ = CIN grades 1, 2 and 3, AIS and invasive cervical cancer. Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. - DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0). - Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection.
时间窗: Up to Month 84
CIN1+ = CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Persistent HPV infection = detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. - DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and 6 and seronegative/positive (sero-/+) at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) - Overall: subjects DNA- at Month 0 and 6 for the corresponding HPV-type, regardless of initial serostatus
Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection.
时间窗: Up to Month 48
CIN1+ = CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Persistent HPV infection = detection of the same HPV type(s) by polymerase chain reaction (PCR) in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. * DNA- and sero-/+: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and 6 and seronegative/positive (sero-/+) at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) * Overall: subjects DNA- at Month 0 and 6 for the corresponding HPV-type, regardless of initial serostatus
Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 and/or With Histopathologically-CIN1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the HPV Type Assignment Algorithm (TAA).
时间窗: Up to Month 48
CIN1+ = CIN grades 1, 2 and 3, AIS and invasive cervical cancer. Persistent cervical HPV infection (6-month definition) = detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. * DNA- and sero-/+: subjects HPV DNA negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative/positive (sero-/+) for HPV-16 and/or HPV-18 by ELISA at baseline (Month 0). * Overall: subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline.
次要结局
- Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Within the Lesional Component of the Cervical Tissue Specimen(Up to Month 84)
- Number of Subjects With Cytological Abnormalities Associated With Oncogenic HPV Types Individually or in Combinations(Up to Month 48)
- Number of Seroconverted Subjects Against HPV-16 in the Immunogenicity Subset.(At pre-vaccination and at Month 7, 12, 18, 24, 36, 48, 60, 72 and 84)
- Number of Seroconverted Subjects Against HPV-18 in the Immunogenicity Subset.(At pre-vaccination and at Month 7, 12, 18, 24, 36, 48, 60, 72 and 84)
- Geometric Mean Concentrations (GMCs) Against HPV-16 Antibody in the Immunogenicity Subset.(At pre-vaccination and at Month 7, 12, 18, 24, 36, 48, 60, 72 and 84)
- Geometric Mean Concentrations (GMCs) Against HPV-18 Antibody in the Immunogenicity Subset.(At pre-vaccination and at Month 7, 12, 18, 24, 36, 48, 60, 72 and 84)
- Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.(Within 7 days (Days 0-6) after vaccination)
- Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18(Up to Month 84)
- Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection Detected Within the Lesional Component of the Cervical Tissue Specimen(Up to Month 84)
- Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types Individually or in Combinations.(Up to Month 84)
- Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Irrespective of HPV Cervical Infection and Irrespective of Baseline HPV DNA Status(Up to Month 84)
- Number of Subjects With Any Cytological Abnormalities Associated With HPV-16 or HPV-18 Cervical Infection(Up to Month 84)
- Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 and/or With Histopathologically-confirmed CIN1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the HPV Type Assignment Algorithm (TAA).(Up to Month 84)
- Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.(Within 7 days (Days 0-6) after vaccination)
- Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs).(Up to Month 48 and up to Month 84)
- Number of Subjects With Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18(Up to Month 84)
- Number of Subjects With Persistent Infection (12-month Definition) With Oncogenic HPV Types Individually or in Combinations.(Up to Month 84)
- Number of Subjects With Histopathologically Confirmed Reduction of Local Cervical Therapy(Up to Month 84)
- Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection(Up to Month 84)
- Number of Subjects With First Colposcopy(Up to Month 84)
- Number of Seroconverted Subjects Against HPV-16 and HPV-18 Viral Neutralization in a Selected Subset of Subjects.(Prior to vaccination and at Months 7, 12, 18, 24, 48 and 84.)
- Geometric Mean Titers (GMTs) Against HPV-16 and HPV-18 Viral Neutralization Antibodies in a Selected Subset of Subjects.(Prior to vaccination and at Months 7, 12, 18, 24, 48 and 84.)
- Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs).(Within 30 days (Days 0 - 29) post-vaccination period.)
- Number of Subjects Reporting New Onset of Autoimmune Disease (NOADs).(Up to Month 48)
- Number of Subjects Reporting Medically Significant Conditions (MAEs).(Up to Month 48)
- Number of Subjects Reporting Related or Fatal Serious Adverse Event.(Up to Month 84)
- Number of Subjects Reporting New Onset of Chronic Disease (NOCDs).(Up to Month 48)
- Number of Subjects With Pregnancies and Their Outcomes.(Up to Month 48)
- Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the Type Assignment Algorithm (TAA)(Up to Month 48)
- Number of Subjects Reporting Any AE/SAE Leading to Premature Discontinuation of the Study.(Up to Month 84)
- Number of Subjects With First Colposcopy(Up to Month 48)
- Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18(Up to Month 48)
- Number of Subjects With Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18(Up to Month 48)
- Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Irrespective of HPV Cervical Infection and Irrespective of Baseline HPV DNA Status(Up to Month 48)
- Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types Individually or in Combinations.(Up to Month 48)
- Number of Subjects With Persistent Infection (12-month Definition) With Oncogenic HPV Types Individually or in Combinations.(Up to Month 48)
- Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)2+ Associated With HPV-16 and/or -18 Cervical Infection Detected Within the Lesional Component of the Cervical Tissue Specimen(Up to Month 48)
- Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Within the Lesional Component of the Cervical Tissue Specimen(Up to Month 48)
- Number of Subjects With Any Cytological Abnormalities Associated With HPV-16 or HPV-18 Cervical Infection(Up to Month 48)
- Number of Subjects With Histopathologically Confirmed Reduction of Local Cervical Therapy(Up to Month 48)
- Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18 and/or With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 and/or -18 Cervical Infection(Up to Month 48)
- Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 or HPV-18 and/or With Histopathologically-confirmed CIN1+ Associated With HPV-16 and/or -18 Cervical Infection Detected Using the HPV Type Assignment Algorithm (TAA).(Up to Month 48)