Clinical trial NCT00779766: Efficacy, Immunogenicity and Safety of GSK Biologicals' HPV GSK 580299 Vaccine in Healthy Chinese Female Subjects
Official title: Efficacy, Immunogenicity and Safety of GlaxoSmithKline Biologicals' HPV GSK 580299 Vaccine in Healthy Chinese Female Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Papillomavirus
Keywords: Human papillomavirus
vaccine
cervical cancer
cervical infection
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-10-24
Enrollment: 6081
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 25
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a multicenter study in which women are planned to receive either the HPV vaccine or control. Study participation will last approximately 72 months and involves a total of thirteen or fourteen scheduled visits.

Originally, the study was planned for 24 months. It was then extended for 2 more years with 4 additional visits (study end at Month 48).

The protocol posting has been updated as the study was extended by additional 2 years with two or three additional visits (study end at Month 72) for subjects who consent to participate in the extension.

Detailed description: This protocol posting has been updated following protocol amendment 6 dated 24 April 2014.

Eligibility criteria: Inclusion Criteria:

* Healthy Chinese females between and including 18 and 25 years of age at the time of the first vaccination.
* 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.
* Healthy subjects as established by medical history and history-directed clinical examination before entering into the study.
* Subjects must not be pregnant. Absence of pregnancy will be verified with a urine pregnancy test.
* Subjects must be of non-childbearing potential, or if of childbearing potential, they must be abstinent or have practiced adequate contraception for 30 days prior to vaccination and agree to continue such precautions for 2 months after completion of the vaccination series.
* Subject must have one single intact cervix.

Exclusion Criteria:

* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* 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 vaccine.
* Concurrently participating in another clinical study, at any time during the study period (up to Month 24), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
* A subject planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the study period and up to two months after the last vaccine dose.
* Pregnant or breastfeeding. Subjects must be at least three months post-pregnancy and not breastfeeding to enter the study.
* Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the protocol during the study period.
* Previous administration of components of the investigational vaccine.
* History of chronic condition(s) requiring treatment such as cancer or autoimmune disease.
* History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the vaccine.
* Hypersensitivity to latex.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Acute disease at the time of enrolment.
* Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.
* History of having had colposcopy or has planned a colposcopy to evaluate an abnormal cervical cytology (Pap smear) test.

Primary outcomes:
measure: Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN1+) and/or Persistent Infection (6 Month+ Definition) Associated With Human Papillomavirus (HPV)-16 and/or HPV-18 at Month 24
timeFrame: At Month 24
measure: Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN1+) and/or Persistent Infection (6 Month+ Definition) Associated With Human Papillomavirus (HPV)-16 and/or HPV-18 at Month 48
timeFrame: At Month 48
measure: Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN1+) and/or Persistent Infection (6 Month+ Definition) Associated With Human Papillomavirus (HPV)-16 and/or HPV-18 at Month 57
timeFrame: At Month 57
measure: Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN1+) and/or Persistent Infection (6 Month+ Definition) Associated With Human Papillomavirus (HPV)-16 and/or HPV-18 at Month 72
timeFrame: At Month 72
Secondary outcomes:
measure: Number of Subjects With Incident Cervical Infection With HPV-16 and/or HPV-18
timeFrame: At Months 24,48, 57 and 72
measure: Number of Subjects With Persistent Cervical Infection (6-month+ Definition) With HPV-16 and/or HPV-18
timeFrame: At Months 24, 48, 57 and 72
measure: Number of Subjects With Persistent Cervical Infection (12-month+ Definition) With HPV-16 and/or HPV-18
timeFrame: At Months 24, 48, 57 and 72
measure: Number of Subjects With Incident Cervical Infection With Any Oncogenic HPV Type
timeFrame: At Months 24, 48, 57 and 72
measure: Number of Subjects With Persistent Cervical Infection (6-month+ Definition) With Any Oncogenic HPV Type
timeFrame: At Months 24, 48, 57 and 72
measure: Number of Subjects With Persistent Cervical Infection (12-month+ Definition) With Any Oncogenic HPV Type
timeFrame: At Months 24,48, 57 and 72
measure: Number of Subjects With Any Cytological Abnormality Including Atypical Squamous Cells of Undetermined Significance (ASC-US+) Associated With HPV-16 and/or HPV-18 Cervical Infection
timeFrame: At Months 24, 48, 57 and 72
measure: Number of Subjects With Any Cytological Abnormality Including Atypical Squamous Cells of Undetermined Significance (ASC-US+) Associated With Any Oncogenic HPV Type
timeFrame: At Months 24, 48, 57 and 72
measure: Number of Subjects With Histopathologically-confirmed CIN1+ Associated With HPV-16 and/or HPV-18 Cervical Infection
timeFrame: At Months 24, 48, 57 and 72
measure: Number of Subjects With Histopathologically-confirmed CIN2+ Associated With HPV-16 and/or HPV-18 Cervical Infection
timeFrame: At Months 24, 48, 57 and 72
measure: Number of Subjects With Histopathologically-confirmed CIN1+ Associated With Cervical Infection With Any Oncogenic HPV Type
timeFrame: At Months 24, 48, 57 and 72
measure: Number of Subjects With Histopathologically-confirmed CIN2+ Associated With Cervical Infection With Any Oncogenic HPV Type
timeFrame: At Months 24, 48, 57 and 72
measure: Number of Subjects With Any and Severe (Grade 3) Solicited Local Symptoms
timeFrame: Within 7 days (Days 0-6) after vaccination
measure: Number of Subjects With Any and Severe (Grade 3) Solicited Local Symptoms, for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline
timeFrame: Within 7 days (Days 0-6) after vaccination
measure: Number of Subjects With Any and Severe (Grade 3) Solicited Local Symptoms, for Subjects Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline
timeFrame: Within 7 days (Days 0-6) after vaccination
measure: Number of Subjects With Any and Severe (Grade 3) Solicited Local Symptoms, for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline
timeFrame: Within 7 days (Days 0-6) after vaccination
measure: Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Solicited General Symptoms.
timeFrame: Within 7 days (Days 0-6) after vaccination
measure: Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Solicited General Symptoms, for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline
timeFrame: Within 7 days (Days 0-6) after vaccination
measure: Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Solicited General Symptoms, for Subjects Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline
timeFrame: Within 7 days (Days 0-6) after vaccination
measure: Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Solicited General Symptoms, for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline
timeFrame: Within 7 days (Days 0-6) after vaccination
measure: Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Unsolicited Adverse Events (AEs)
timeFrame: Within Days 0-29 after vaccination
measure: Number of Subjects With Unsolicited Adverse Events for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline
timeFrame: Within Days 0-29 after vaccination
measure: Number of Subjects With Unsolicited Adverse Events for Subjects Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline
timeFrame: Within Days 0-29 after vaccination
measure: Number of Subjects With Unsolicited Adverse Events for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline
timeFrame: Within Days 0-29 after vaccination
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: From Day 0 to Month 72
measure: Number of Subjects With Medically Significant Conditions (MSC) Regardless of Causal Relationship to Vaccination and Intensity
timeFrame: From Day 0 to Month 72
measure: Number of Subjects With Medically Significant Conditions Regardless of Causal Relationship to Vaccination and Intensity for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline
timeFrame: From Day 0 to Month 72
measure: Number of Subjects With Medically Significant Conditions Regardless of Causal Relationship to Vaccination and Intensity for Subjects Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline
timeFrame: From Day 0 to Month 72
measure: Number of Subjects With Medically Significant Conditions Regardless of Causal Relationship to Vaccination and Intensity for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline
timeFrame: From Day 0 to Month 72
measure: Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies
timeFrame: From Day 0 to Month 72
measure: Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline
timeFrame: From Day 0 to Month 72
measure: Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline
timeFrame: From Day 0 to Month 72
measure: Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline
timeFrame: From Day 0 to Month 72
measure: Number of Subjects With HPV-16 Antibody Concentration Equal to or Above the Assay Cut-off Value, by Pre-vaccination Status
timeFrame: at Months 0 (PRE), 7, 12, 24, 36, 48 and 72
measure: Number of Subjects With HPV-18 Antibody Concentration Equal to or Above the Assay Cut-off Value, by Pre-vaccination Status
timeFrame: at Months 0 (PRE), 7, 12, 24, 36, 48 and 72
measure: Geometric Mean Titers for HPV-16/HPV-18 Antibodies, by Pre-vaccination Status
timeFrame: at Months 0 (PRE), 7, 12, 24, 36, 48 and 72
Other outcomes:
Locations:
city: Jintan
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Lianshui
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Xuzhou
country: China
facility: GSK Investigational Site
state: Jiangsu
city: Yancheng
country: China
facility: GSK Investigational Site
state: Jiangsu
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Zhao FH, Zhu FC, Chen W, Li J, Hu YM, Hong Y, Zhang YJ, Pan QJ, Zhu JH, Zhang X, Chen Y, Tang H, Zhang H, Durand C, Datta SK, Struyf F, Bi D; HPV-039 study group. Baseline prevalence and type distribution of human papillomavirus in healthy Chinese women aged 18-25 years enrolled in a clinical trial. Int J Cancer. 2014 Dec 1;135(11):2604-11. doi: 10.1002/ijc.28896. Epub 2014 May 20.
citation: Zhu FC, Chen W, Hu YM, Hong Y, Li J, Zhang X, Zhang YJ, Pan QJ, Zhao FH, Yu JX, Zhang YS, Yang X, Zhang CF, Tang H, Zhang H, Lebacq M, David MP, Datta SK, Struyf F, Bi D, Descamps D; HPV-039 study group. Efficacy, immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Chinese women aged 18-25 years: results from a randomized controlled trial. Int J Cancer. 2014 Dec 1;135(11):2612-22. doi: 10.1002/ijc.28897. Epub 2014 May 20.
citation: Zhu FC, Hu SY, Hong Y, Hu YM, Zhang X, Zhang YJ, Pan QJ, Zhang WH, Zhao FH, Zhang CF, Yang X, Yu JX, Zhu J, Zhu Y, Chen F, Zhang Q, Wang H, Wang C, Bi J, Xue S, Shen L, Zhang YS, He Y, Tang H, Karkada N, Suryakiran P, Bi D, Struyf F. Efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine in Chinese women aged 18-25 years: event-triggered analysis of a randomized controlled trial. Cancer Med. 2017 Jan;6(1):12-25. doi: 10.1002/cam4.869. Epub 2016 Dec 20.
citation: Welby S, Rosillon D, Feng Y, Borys D. Progression from human papillomavirus (HPV) infection to cervical lesion or clearance in women (18-25 years): Natural history study in the control arm subjects of AS04-HPV-16/18 vaccine efficacy study in China between 2008 and 2016. Expert Rev Vaccines. 2022 Mar;21(3):407-413. doi: 10.1080/14760584.2022.2021077. Epub 2022 Jan 24.
citation: Zhao S, Hu S, Xu X, Zhang X, Pan Q, Chen F, Zhao F. Impact of HPV-16/18 AS04-adjuvanted vaccine on preventing subsequent infection and disease after excision treatment: post-hoc analysis from a randomized controlled trial. BMC Infect Dis. 2020 Nov 16;20(1):846. doi: 10.1186/s12879-020-05560-z.
citation: Hu S, Xu X, Zhu F, Hong Y, Hu Y, Zhang X, Pan Q, Zhang W, Zhang C, Yang X, Yu J, Zhu J, Zhu Y, Chen F, Zhao S, Karkada N, Tang H, Bi D, Struyf F, Zhao F. Efficacy of the AS04-adjuvanted HPV-16/18 vaccine in young Chinese women with oncogenic HPV infection at baseline: post-hoc analysis of a randomized controlled trial. Hum Vaccin Immunother. 2021 Apr 3;17(4):955-964. doi: 10.1080/21645515.2020.1829411. Epub 2020 Nov 12.
citation: Hu Y, Zhang X, He Y, Ma Z, Xie Y, Lu X, Xu Y, Zhang Y, Jiang Y, Xiao H, Struyf F, Folschweiller N, Jiang J, Poncelet S, Karkada N, Jastorff A, Borys D. Long-term persistence of immune response to the AS04-adjuvanted HPV-16/18 vaccine in Chinese girls aged 9-17 years: Results from an 8-9-year follow-up phase III open-label study. Asia Pac J Clin Oncol. 2020 Dec;16(6):392-399. doi: 10.1111/ajco.13398. Epub 2020 Aug 11.
citation: 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.
citation: Zhu FC, Hu SY, Hong Y, Hu YM, Zhang X, Zhang YJ, Pan QJ, Zhang WH, Zhao FH, Zhang CF, Yang X, Yu JX, Zhu J, Zhu Y, Chen F, Zhang Q, Wang H, Wang C, Bi J, Xue S, Shen L, Zhang YS, He Y, Tang H, Karkada N, Suryakiran P, Bi D, Struyf F. Efficacy, immunogenicity and safety of the AS04-HPV-16/18 vaccine in Chinese women aged 18-25 years: End-of-study results from a phase II/III, randomised, controlled trial. Cancer Med. 2019 Oct;8(14):6195-6211. doi: 10.1002/cam4.2399. Epub 2019 Jul 15.
citation: Zhu F, Li J, Hu Y, Zhang X, Yang X, Zhao H, Wang J, Yang J, Xia G, Dai Q, Tang H, Suryakiran P, Datta SK, Descamps D, Bi D, Struyf F. Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Chinese girls and women aged 9 to 45 years. Hum Vaccin Immunother. 2014;10(7):1795-806. doi: 10.4161/hv.28702.