Study to Evaluate the Efficacy of the Human Papillomavirus Vaccine in Healthy Adult Women of 26 Years of Age and Older
2019年12月27日 更新者：GlaxoSmithKline
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
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.
調査の概要
詳細な説明
The Protocol Posting has been updated due to protocol amendment 5 and in order to comply with the FDA Amendment Act, Sep 2007.
研究の種類
介入
入学 (実際)
5752
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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California
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Fountain Valley、California、アメリカ、92708
- GSK Investigational Site
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Colorado
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Aurora、Colorado、アメリカ、80045
- GSK Investigational Site
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Golden、Colorado、アメリカ、80401
- GSK Investigational Site
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Florida
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Coral Gables、Florida、アメリカ、33134
- GSK Investigational Site
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Miami、Florida、アメリカ、33136
- GSK Investigational Site
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Georgia
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Augusta、Georgia、アメリカ、30912
- GSK Investigational Site
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Iowa
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Iowa City、Iowa、アメリカ、52242
- GSK Investigational Site
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Kansas
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Wichita、Kansas、アメリカ、67207
- GSK Investigational Site
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Kentucky
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Bardstown、Kentucky、アメリカ、40004
- GSK Investigational Site
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Louisville、Kentucky、アメリカ、40202
- GSK Investigational Site
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Minnesota
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Chaska、Minnesota、アメリカ、55318
- GSK Investigational Site
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Nebraska
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Omaha、Nebraska、アメリカ、68131
- GSK Investigational Site
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New Hampshire
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Lebanon、New Hampshire、アメリカ、03756
- GSK Investigational Site
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New Mexico
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Albuquerque、New Mexico、アメリカ、87131
- GSK Investigational Site
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New York
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Syracuse、New York、アメリカ、13057
- GSK Investigational Site
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North Carolina
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Chapel Hill、North Carolina、アメリカ、27514
- GSK Investigational Site
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New Bern、North Carolina、アメリカ、28562
- GSK Investigational Site
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Ohio
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Akron、Ohio、アメリカ、44311
- GSK Investigational Site
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Cleveland、Ohio、アメリカ、44122
- GSK Investigational Site
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Oklahoma
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Tulsa、Oklahoma、アメリカ、74105
- GSK Investigational Site
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Oregon
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Portland、Oregon、アメリカ、97210
- GSK Investigational Site
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Pennsylvania
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Carnegie、Pennsylvania、アメリカ、15106
- GSK Investigational Site
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Erie、Pennsylvania、アメリカ、16508
- GSK Investigational Site
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Erie、Pennsylvania、アメリカ、16507
- GSK Investigational Site
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Philadelphia、Pennsylvania、アメリカ、19107
- GSK Investigational Site
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Pittsburgh、Pennsylvania、アメリカ、15236
- GSK Investigational Site
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Pittsburgh、Pennsylvania、アメリカ、15213
- GSK Investigational Site
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Wexford、Pennsylvania、アメリカ、15090
- GSK Investigational Site
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Texas
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Austin、Texas、アメリカ、78705
- GSK Investigational Site
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Houston、Texas、アメリカ、77030
- GSK Investigational Site
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Houston、Texas、アメリカ、77004
- GSK Investigational Site
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Utah
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Salt Lake City、Utah、アメリカ、84109
- GSK Investigational Site
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Salt Lake City、Utah、アメリカ、84121
- GSK Investigational Site
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South Jordan、Utah、アメリカ、84095
- GSK Investigational Site
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Washington
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Wenatchee、Washington、アメリカ、98801
- GSK Investigational Site
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Wisconsin
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La Crosse、Wisconsin、アメリカ、54601
- GSK Investigational Site
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Aberdeen、イギリス、AB25 7ZD
- GSK Investigational Site
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Cardiff、イギリス、CF14 4XN
- GSK Investigational Site
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Gateshead、イギリス、NE9 6SX
- GSK Investigational Site
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London、イギリス、EC1M 6BQ
- GSK Investigational Site
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Manchester、イギリス、M13 9WL
- GSK Investigational Site
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Middlesex
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Northwood、Middlesex、イギリス、HA6 2RN
- GSK Investigational Site
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Amsterdam、オランダ、1007 MB
- GSK Investigational Site
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Delft、オランダ、2625 AD
- GSK Investigational Site
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Rotterdam、オランダ、3015 CE
- GSK Investigational Site
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Victoria
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Parkville、Victoria、オーストラリア、3052
- GSK Investigational Site
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Western Australia
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Perth、Western Australia、オーストラリア
- GSK Investigational Site
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Quebec、カナダ、G1S 2L6
- GSK Investigational Site
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Alberta
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Edmonton、Alberta、カナダ、T6G 2C8
- GSK Investigational Site
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British Columbia
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Vancouver、British Columbia、カナダ、V6H 3N1
- GSK Investigational Site
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Nova Scotia
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Halifax、Nova Scotia、カナダ、B3H 2Y9
- GSK Investigational Site
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Truro、Nova Scotia、カナダ、B2N 1L2
- GSK Investigational Site
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Ontario
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Waterloo、Ontario、カナダ、N2L 6H6
- GSK Investigational Site
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Quebec
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Sherbrooke、Quebec、カナダ、J1H 1Z1
- GSK Investigational Site
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Singapore、シンガポール、119074
- GSK Investigational Site
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Singapore、シンガポール、229899
- GSK Investigational Site
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Bangkok、タイ、10400
- GSK Investigational Site
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Bangkok、タイ、10700
- GSK Investigational Site
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Laguna、フィリピン
- GSK Investigational Site
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San Pablo City、フィリピン
- GSK Investigational Site
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Taft Avenue, Manila、フィリピン、1700
- GSK Investigational Site
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Lima、ペルー
- GSK Investigational Site
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Almada、ポルトガル、2805-267 Almada
- GSK Investigational Site
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Coimbra、ポルトガル、3000-075 Coimbra
- GSK Investigational Site
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Lisboa、ポルトガル、1200-831 Lisboa
- GSK Investigational Site
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Porto、ポルトガル、4200-023 Porto
- GSK Investigational Site
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Setúbal、ポルトガル、2910-446 Setúbal
- GSK Investigational Site
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Jojutla / Morelos、メキシコ
- GSK Investigational Site
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Morelos
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Cuenavaca、Morelos、メキシコ、62430
- GSK Investigational Site
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Ekaterinburg、ロシア連邦、620073
- GSK Investigational Site
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Moscow、ロシア連邦、117997
- GSK Investigational Site
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Moscow、ロシア連邦、115 478
- GSK Investigational Site
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Moscow、ロシア連邦、109263
- GSK Investigational Site
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Sankt-Petersburg、ロシア連邦、190020
- GSK Investigational Site
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Sankt-Petersburg、ロシア連邦、199034
- GSK Investigational Site
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
26年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
はい
受講資格のある性別
女性
説明
Inclusion criteria:
- 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.
Exclusion criteria:
- 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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：防止
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：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.
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Subjects were planned to receive three doses of the study vaccine administered intramuscularly according to a 0, 1, 6 month vaccination schedule.
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プラセボコンパレーター：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.
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Subjects were planned to receive three doses of the control vaccine administered intramuscularly according to a 0, 1, 6 month vaccination schedule.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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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.
時間枠：Up to Month 48
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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.
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Up to Month 48
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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).
時間枠：Up to Month 48
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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.
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Up to Month 48
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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.
時間枠：Up to Month 84
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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
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Up to Month 84
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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).
時間枠：Up to Month 84
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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.
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Up to Month 84
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18
時間枠：Up to Month 48
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Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval. Detection was done in:
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Up to Month 48
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Number of Subjects With Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18
時間枠：Up to Month 48
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Persistent cervical HPV infection (12-month definition) was defined as the detection of the same HPV type(s) PCR in cervical samples at all available time points over approximately a 12-month interval (evaluations are planned at approximately 6-month intervals).
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Up to Month 48
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Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types Individually or in Combinations.
時間枠：Up to Month 48
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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. Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Detection was done in subjects HPV DNA- for the corresponding HPV type at baseline (at month 0 and Month 6) regardless of initial serostatus. HPV-HRW=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18. HPV-HR=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. |
Up to Month 48
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Number of Subjects With Persistent Infection (12-month Definition) With Oncogenic HPV Types Individually or in Combinations.
時間枠：Up to Month 48
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Persistent HPV infection (12-month definition) = detection of the same HPV type(s) by PCR in cervical samples at available time points over approximately a 12-month interval (evaluations are planned at approximately 6-month intervals). Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. subjects HPV DNA- for the corresponding HPV type at Month 0 6, regardless of initial serostatus. HPV-HRW=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HPV-HR=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 , 68 |
Up to Month 48
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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
時間枠：Up to Month 48
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CIN2+ was defined as CIN grades 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done in:
Note: Results for seropositive status were not analysed. |
Up to Month 48
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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
時間枠：Up to Month 48
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CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done in:
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Up to Month 48
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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
時間枠：Up to Month 48
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CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus. |
Up to Month 48
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Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Irrespective of HPV Cervical Infection and Irrespective of Baseline HPV DNA Status
時間枠：Up to Month 48
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CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done on all subjects irrespective of their baseline HPV DNA status. |
Up to Month 48
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Number of Subjects With Any Cytological Abnormalities Associated With HPV-16 or HPV-18 Cervical Infection
時間枠：Up to Month 48
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Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-US). Detection was done in:
Results for seropositive status were not analysed. |
Up to Month 48
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Number of Subjects With Cytological Abnormalities Associated With Oncogenic HPV Types Individually or in Combinations
時間枠：Up to Month 48
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Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Detection was done in subjects who were HPV DNA negative for the corresponding HPV type at baseline (at month 0 and Month 6) regardless of initial serostatus. HRW-HPV= All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HPV-HR= High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 |
Up to Month 48
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Number of Subjects With Histopathologically Confirmed Reduction of Local Cervical Therapy
時間枠：Up to Month 48
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Detection was done on all subjects irrespective of their baseline HPV DNA status.
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Up to Month 48
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Number of Subjects With First Colposcopy
時間枠：Up to Month 48
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Detection was done on all subjects irrespective of their baseline HPV DNA status.
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Up to Month 48
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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
時間枠：Up to Month 48
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Persistent cervical HPV infection (6-month definition) was defined as the 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. CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus. |
Up to Month 48
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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).
時間枠：Up to Month 48
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Persistent cervical HPV infection (6-month definition) was defined as the 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. Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus. The lesion was assigned to an HPV type found in the lesion if (1) the same HPV type was found in at least 1 of the 2 (closest) preceding cytology samples, or (2) none of the HPV types found in the lesion were found in any of the 2 preceding cytology samples (isolate HPV types) |
Up to Month 48
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Number of Seroconverted Subjects Against HPV-16 in the Immunogenicity Subset.
時間枠：At pre-vaccination and at Month 7, 12, 18, 24, 36, 48, 60, 72 and 84
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Seroconversion was defined as the appearance of antibodies (i.e.; titre greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. HPV-16 assay cut-off value was defined as greater than or equal to 8 ELISA units per millilitre (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 8 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 8 EL.U/mL prior to vaccination. Immuno subset=subjects from selected sites N≥1000, at least 250 per region |
At pre-vaccination and at Month 7, 12, 18, 24, 36, 48, 60, 72 and 84
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Number of Seroconverted Subjects Against HPV-18 in the Immunogenicity Subset.
時間枠：At pre-vaccination and at Month 7, 12, 18, 24, 36, 48, 60, 72 and 84
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Seroconversion was defined as the appearance of antibodies (i.e.; titre greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. HPV-18 assay cut-off value was defined as greater than or equal to 7 ELISA units per millilitre (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 7 EL.U/mL prior to vaccination. Immuno subset=subjects from selected sites N≥1000, at least 250 per region |
At pre-vaccination and at Month 7, 12, 18, 24, 36, 48, 60, 72 and 84
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Geometric Mean Concentrations (GMCs) Against HPV-16 Antibody in the Immunogenicity Subset.
時間枠：At pre-vaccination and at Month 7, 12, 18, 24, 36, 48, 60, 72 and 84
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GMCs were expressed in ELISA units per milliliter (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 8 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 8 EL.U/mL prior to vaccination. Immuno subset=subjects from selected sites (N≥1000, at least 250 per region) |
At pre-vaccination and at Month 7, 12, 18, 24, 36, 48, 60, 72 and 84
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Geometric Mean Concentrations (GMCs) Against HPV-18 Antibody in the Immunogenicity Subset.
時間枠：At pre-vaccination and at Month 7, 12, 18, 24, 36, 48, 60, 72 and 84
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GMCs were expressed in ELISA units per milliliter (EL.U/mL). Seronegative (Sero-) subjects are subjects who had an antibody concentration below 7 EL.U/mL prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody concentration equal to or above 7 EL.U/mL prior to vaccination. Immuno subset=subjects from selected sites (N≥1000, at least 250 per region) |
At pre-vaccination and at Month 7, 12, 18, 24, 36, 48, 60, 72 and 84
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Number of Seroconverted Subjects Against HPV-16 and HPV-18 Viral Neutralization in a Selected Subset of Subjects.
時間枠：Prior to vaccination and at Months 7, 12, 18, 24, 48 and 84.
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Seroconversion was defined as the appearance of antibodies (i.e.; titre greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination.
HPV-16/18 assay cut-off value was defined as greater than or equal to 40 Estimated dose 50% (ED50).
Sero- subjects are subjects who had an antibody concentration below 40 ED50 prior to vaccination.
Sero+ subjects are subjects who had an antibody concentration equal to or above 50 ED50 prior to vaccination.
ED50 = the estimated serum dilution reducing the signal generated by viral infection by 50%
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Prior to vaccination and at Months 7, 12, 18, 24, 48 and 84.
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Geometric Mean Titers (GMTs) Against HPV-16 and HPV-18 Viral Neutralization Antibodies in a Selected Subset of Subjects.
時間枠：Prior to vaccination and at Months 7, 12, 18, 24, 48 and 84.
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Titers are expressed as geometric mean antibody titers (GMTs). Seronegative (Sero-) subjects are subjects who had an antibody titer below 40 ED50 prior to vaccination. Seropositive (Sero+) subjects are subjects who had an antibody titer equal to or above 40 ED50 prior to vaccination. ED50 = Estimated dose 50%, the estimated serum dilution reducing the signal generated by viral infection by 50% |
Prior to vaccination and at Months 7, 12, 18, 24, 48 and 84.
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Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms.
時間枠：Within 7 days (Days 0-6) after vaccination
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Solicited local symptoms assessed were pain, redness and swelling.
Any was defined as any solicited local symptom reported irrespective of intensity.
Grade 3 pain was defined as pain that prevented normal activity.
Grade 3 redness and swelling was defined as redness/swelling above 50 millimeter (mm).
|
Within 7 days (Days 0-6) after vaccination
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Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.
時間枠：Within 7 days (Days 0-6) after vaccination
|
Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and fever (Fever = axillary temperature above 37.5 degrees Celsius (°C)).
Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination.
Related = symptoms considered by the investigator to have a causal relationship to vaccination.
Grade 3 symptoms = symptoms that prevented normal activity.
Grade 3 urticaria = urticaria distributed on at least 4 body areas.
Grade 3 fever = axillary temperature above 39.0°C.
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Within 7 days (Days 0-6) after vaccination
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Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs).
時間枠：Within 30 days (Days 0 - 29) post-vaccination period.
|
An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Grade 3 unsolicited AE = an event that prevented normal activity. A related AE = event assessed by the investigator as causally related to the study vaccination. |
Within 30 days (Days 0 - 29) post-vaccination period.
|
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Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs).
時間枠：Up to Month 48 and up to Month 84
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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.
A related SAE was defined as an event assessed by the investigator as causally related to the study vaccination.
|
Up to Month 48 and up to Month 84
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Number of Subjects Reporting Related or Fatal Serious Adverse Event.
時間枠：Up to Month 84
|
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
|
Up to Month 84
|
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Number of Subjects Reporting Any AE/SAE Leading to Premature Discontinuation of the Study.
時間枠：Up to Month 84
|
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. |
Up to Month 84
|
|
Number of Subjects Reporting New Onset of Chronic Disease (NOCDs).
時間枠：Up to Month 48
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NOCDs include autoimmune disorders, asthma and type I diabetes.
|
Up to Month 48
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Number of Subjects Reporting New Onset of Autoimmune Disease (NOADs).
時間枠：Up to Month 48
|
Up to Month 48
|
|
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Number of Subjects Reporting Medically Significant Conditions (MAEs).
時間枠：Up to Month 48
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Medically significant conditions were defined as: 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 diseases.
Common diseases included: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury.
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Up to Month 48
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Number of Subjects With Pregnancies and Their Outcomes.
時間枠：Up to Month 48
|
Pregnancy outcomes are live infant, premature live infant, elective termination, ectopic pregnancy, 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).
|
Up to Month 48
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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)
時間枠：Up to Month 48
|
CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer. Detection was done on subjects DNA- at Month 0 and Month 6 for the corresponding HPV-type and regardless of initial serostatus at baseline. TAA: Type assignment algorithm. The lesion was assigned to an HPV type found in the lesion if
|
Up to Month 48
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Number of Subjects With Persistent Infection (6-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18
時間枠：Up to Month 84
|
Persistent cervical HPV infection (6-month definition) was defined as the detection of the same HPV type(s) by PCR in cervical samples at 2 consecutive evaluations over approximately a 6-month interval.
Detection was done in: - 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.
|
Up to Month 84
|
|
Number of Subjects With Persistent Infection (12-month Definition) With Human Papillomavirus (HPV)-16 or HPV-18
時間枠：Up to Month 84
|
Persistent cervical HPV infection (12-month definition) was defined as the detection of the same HPV type(s) PCR in cervical samples at all available time points over approximately a 12-month interval (evaluations are planned at approximately 6-month intervals).
- 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.
|
Up to Month 84
|
|
Number of Subjects With Persistent Infection (6-month Definition) With Oncogenic HPV Types Individually or in Combinations.
時間枠：Up to Month 84
|
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.
Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Detection was done in subjects HPV DNA- for the corresponding HPV type at baseline (at month 0 and Month 6) regardless of initial serostatus.
HPV-HRW=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18.
HPV-HR=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
|
Up to Month 84
|
|
Number of Subjects With Persistent Infection (12-month Definition) With Oncogenic HPV Types Individually or in Combinations.
時間枠：Up to Month 84
|
Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
subjects HPV DNA- for the corresponding HPV type at Month 0 6, regardless of initial serostatus.
HPV-HRW=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HPV-HR=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 , 68
|
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
時間枠：Up to Month 84
|
CIN2+ was defined as CIN grades 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.
Detection was done in: - DNA- and sero-: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (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.
Note: Results for seropositive status were not analysed.
|
Up to Month 84
|
|
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
時間枠：Up to Month 84
|
CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.
Detection was done in: - DNA- and sero-/+: subjects HPV deoxyribonucleic acid (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 Enzyme-linked Immunosorbent Assay (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.
|
Up to Month 84
|
|
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
時間枠：Up to Month 84
|
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
時間枠：Up to Month 84
|
CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.
Detection was done on all subjects irrespective of their baseline HPV DNA status.
|
Up to Month 84
|
|
Number of Subjects With Any Cytological Abnormalities Associated With HPV-16 or HPV-18 Cervical Infection
時間枠：Up to Month 84
|
Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-US).
Detection was done in: - DNA- and sero-: subjects HPV deoxyribonucleic acid (DNA) negative (DNA-) at Month 0 and Month 6 for the corresponding HPV-type and seronegative (sero-) for HPV-16 and/or HPV-18 by Enzyme-linked Immunosorbent Assay (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.
Results for seropositive status were not analysed.
|
Up to Month 84
|
|
Number of Subjects With Cytological Abnormalities Associated With Oncogenic HPV Types Individually or in Combinations
時間枠：Up to Month 48
|
Oncogenic HPV types included HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
Detection was done in subjects who were HPV DNA negative for the corresponding HPV type at baseline (at month 0 and Month 6) regardless of initial serostatus.
HRW-HPV= All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HPV-HR= High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68
|
Up to Month 48
|
|
Number of Subjects With Histopathologically Confirmed Reduction of Local Cervical Therapy
時間枠：Up to Month 84
|
Detection was done on all subjects irrespective of their baseline HPV DNA status.
|
Up to Month 84
|
|
Number of Subjects With First Colposcopy
時間枠：Up to Month 84
|
Detection was done on all subjects irrespective of their baseline HPV DNA status.
|
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
時間枠：Up to Month 84
|
Persistent cervical HPV infection (6-month definition) was defined as the 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.
CIN1+ was defined as CIN grades 1, 2 and 3, adenocarcinoma in situ (AIS) and invasive cervical cancer.
Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus.
|
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).
時間枠：Up to Month 84
|
Persistent cervical HPV infection (6-month definition) was defined as the 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.
Detection was done on all subjects irrespective of their baseline HPV DNA and serostatus.
The lesion was assigned to an HPV type found in the lesion if (1) the same HPV type was found in at least 1 of the 2 (closest) preceding cytology samples, or (2) none of the HPV types found in the lesion were found in any of the 2 preceding cytology samples (isolate HPV types)
|
Up to Month 84
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Verstraeten T, Descamps D, David MP, Zahaf T, Hardt K, Izurieta P, Dubin G, Breuer T. Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines. Vaccine. 2008 Dec 2;26(51):6630-8. doi: 10.1016/j.vaccine.2008.09.049.
- 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.
- Descamps D, Hardt K, Spiessens B, Izurieta P, Verstraeten T, Breuer T, Dubin G. Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials. Hum Vaccin. 2009 May;5(5):332-40. doi: 10.4161/hv.5.5.7211. Epub 2009 May 20.
- Skinner SR, Szarewski A, Romanowski B, Garland SM, Lazcano-Ponce E, Salmeron J, Del Rosario-Raymundo MR, Verheijen RH, Quek SC, da Silva DP, Kitchener H, Fong KL, Bouchard C, Money DM, Ilancheran A, Cruickshank ME, Levin MJ, Chatterjee A, Stapleton JT, Martens M, Quint W, David MP, Meric D, Hardt K, Descamps D, Geeraerts B, Struyf F, Dubin G; VIVIANE Study Group. Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 4-year interim follow-up of the phase 3, double-blind, randomised controlled VIVIANE study. Lancet. 2014 Dec 20;384(9961):2213-27. doi: 10.1016/S0140-6736(14)60920-X. Epub 2014 Sep 1.
- Wheeler CM, Skinner SR, Del Rosario-Raymundo MR, Garland SM, Chatterjee A, Lazcano-Ponce E, Salmeron J, McNeil S, Stapleton JT, Bouchard C, Martens MG, Money DM, Quek SC, Romanowski B, Vallejos CS, Ter Harmsel B, Prilepskaya V, Fong KL, Kitchener H, Minkina G, Lim YKT, Stoney T, Chakhtoura N, Cruickshank ME, Savicheva A, da Silva DP, Ferguson M, Molijn AC, Quint WGV, Hardt K, Descamps D, Suryakiran PV, Karkada N, Geeraerts B, Dubin G, Struyf F; VIVIANE Study Group. Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years: 7-year follow-up of the phase 3, double-blind, randomised controlled VIVIANE study. Lancet Infect Dis. 2016 Oct;16(10):1154-1168. doi: 10.1016/S1473-3099(16)30120-7. Epub 2016 Jun 28.
- Wheeler CM, Struyf F; HPV-015 study group. The safety of Cervarix? - Authors' reply. Lancet Infect Dis. 2017 Jan;17(1):20-21. doi: 10.1016/S1473-3099(16)30540-0. No abstract available.
- Rosillon D, Baril L, Del Rosario-Raymundo MR, Wheeler CM, Skinner SR, Garland SM, Salmeron J, Lazcano-Ponce E, Vallejos CS, Stoney T, Ter Harmsel B, Lim TYK, Quek SC, Minkina G, McNeil SA, Bouchard C, Fong KL, Money D, Ilancheran A, Savicheva A, Cruickshank M, Chatterjee A, Fiander A, Martens M, Bozonnat MC, Struyf F, Dubin G, Castellsague X. Risk of newly detected infections and cervical abnormalities in adult women seropositive or seronegative for naturally acquired HPV-16/18 antibodies. Cancer Med. 2019 Aug;8(10):4938-4953. doi: 10.1002/cam4.1879. Epub 2019 Jul 5.
- Skinner SR, Wheeler CM, Romanowski B, Castellsague X, Lazcano-Ponce E, Del Rosario-Raymundo MR, Vallejos C, Minkina G, Pereira Da Silva D, McNeil S, Prilepskaya V, Gogotadze I, Money D, Garland SM, Romanenko V, Harper DM, Levin MJ, Chatterjee A, Geeraerts B, Struyf F, Dubin G, Bozonnat MC, Rosillon D, Baril L; VIVIANE Study Group. Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study. Int J Cancer. 2016 May 15;138(10):2428-38. doi: 10.1002/ijc.29971.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2006年2月16日
一次修了 (実際)
2014年1月29日
研究の完了 (実際)
2014年1月29日
試験登録日
最初に提出
2006年2月17日
QC基準を満たした最初の提出物
2006年2月17日
最初の投稿 (見積もり)
2006年2月20日
学習記録の更新
投稿された最後の更新 (実際)
2020年1月2日
QC基準を満たした最後の更新が送信されました
2019年12月27日
最終確認日
2019年12月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 104820
- 2005-002546-20 (EudraCT番号)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
はい
IPD プランの説明
IPD is available via the Clinical Study Data Request site (click on the link provided below)
IPD 共有時間枠
IPD is available via the Clinical Study Data Request site (click on the link provided below)
IPD 共有アクセス基準
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place.
Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
試験データ・資料
-
インフォームド コンセント フォーム
情報識別子：104820情報コメント：For additional information about this study please refer to the GSK Clinical Study Register
-
臨床研究報告書
情報識別子：104820情報コメント：For additional information about this study please refer to the GSK Clinical Study Register
-
研究プロトコル
情報識別子：104820情報コメント：For additional information about this study please refer to the GSK Clinical Study Register
-
データセット仕様
情報識別子：104820情報コメント：For additional information about this study please refer to the GSK Clinical Study Register
-
個人参加者データセット
情報識別子：104820情報コメント：For additional information about this study please refer to the GSK Clinical Study Register
-
統計分析計画
情報識別子：104820情報コメント：For additional information about this study please refer to the GSK Clinical Study Register
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。