Efficacy, Immunogenicity and Safety of GSK Biologicals' HPV GSK 580299 Vaccine in Healthy Chinese Female Subjects
May 3, 2019 updated by: GlaxoSmithKline
Efficacy, Immunogenicity and Safety of GlaxoSmithKline Biologicals' HPV GSK 580299 Vaccine in Healthy Chinese Female Subjects
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This protocol posting has been updated following protocol amendment 6 dated 24 April 2014.
Study Type
Interventional
Enrollment (Actual)
6081
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Jiangsu
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Jintan, Jiangsu, China, 213200
- GSK Investigational Site
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Lianshui, Jiangsu, China
- GSK Investigational Site
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Xuzhou, Jiangsu, China, 221006
- GSK Investigational Site
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Yancheng, Jiangsu, China, 224500
- GSK Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 25 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
Female
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Cervarix Group
Subjects received 3 doses of Cervarix™ vaccine.
Cervarix™ vaccine was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month 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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Placebo Comparator: Placebo Group
Subjects received 3 doses of placebo.
Placebo was administered intramuscularly in the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.
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Subjects were planned to receive three doses of the placebo control administered intramuscularly according to a 0, 1, 6 month vaccination schedule.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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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
Time Frame: At Month 24
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CIN1+ = CIN 1, 2, and 3, low/high-grade cervical glandular intraepithelial neoplasia (L/HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer.
Persistent infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an interval of approximately 6 months.
The analyses were done on subjects HPV DNA negative at baseline (Month 0) and Month 6 and seronegative at baseline (Month 0) or on subjects DNA negative at baseline (Month 0) and Month 6, regardless of initial serostatus.
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At Month 24
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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
Time Frame: At Month 48
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CIN1+ = CIN 1, 2, and 3, low/high-grade cervical glandular intraepithelial neoplasia (L/HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer.
Persistent infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an interval of approximately 6 months.
The analyses were done on subjects HPV DNA negative at baseline (Month 0) and Month 6 and seronegative at baseline (Month 0) or on subjects DNA negative at baseline (Month 0) and Month 6, regardless of initial serostatus.
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At Month 48
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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
Time Frame: At Month 57
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CIN1+ = CIN 1, 2, and 3, low/high-grade cervical glandular intraepithelial neoplasia (L/HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer.
Persistent infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an interval of approximately 6 months.
The analyses were done on subjects HPV DNA negative at baseline (Month 0) and Month 6 and seronegative at baseline (Month 0) or on subjects DNA negative at baseline (Month 0) and Month 6, regardless of initial serostatus.
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At Month 57
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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
Time Frame: At Month 72
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CIN1+ = CIN 1, 2, and 3, low/high-grade cervical glandular intraepithelial neoplasia (L/HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer.
Persistent infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the 2 positive DNA samples, over an interval of approximately 6 months.
The analyses were done on subjects HPV DNA negative at baseline (Month 0) and Month 6 and seronegative at baseline (Month 0) or on subjects DNA negative at baseline (Month 0) and Month 6, regardless of initial serostatus.
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At Month 72
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Number of Subjects With Incident Cervical Infection With HPV-16 and/or HPV-18
Time Frame: At Months 24,48, 57 and 72
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HPV-16 and/or HPV-18 incident infection is defined as at least one positive HPV-16 or HPV-18 DNA PCR assay at the time point considered.
- DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) - Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
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At Months 24,48, 57 and 72
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Number of Subjects With Persistent Cervical Infection (6-month+ Definition) With HPV-16 and/or HPV-18
Time Frame: At Months 24, 48, 57 and 72
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Persistent HPV-16 and/or HPV-18 infection (6-month+ definition) = at least 2 positive HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) assays for the same viral genotype with no negative DNA sample between the two positive DNA samples, over an interval of approximately 6 months.
Subjects had at least 5 months of follow-up after Month 12. DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by ELISA Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
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At Months 24, 48, 57 and 72
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Number of Subjects With Persistent Cervical Infection (12-month+ Definition) With HPV-16 and/or HPV-18
Time Frame: At Months 24, 48, 57 and 72
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Persistent infection (12-month+ definition) is defined as the detection of the same HPV type(s) (by PCR) in cervical samples at all available time points over an interval of approximately 12 months.
Subjects had at least 10 months of follow-up after Month 12. DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA).
Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
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At Months 24, 48, 57 and 72
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Number of Subjects With Incident Cervical Infection With Any Oncogenic HPV Type
Time Frame: At Months 24, 48, 57 and 72
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Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination.
Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
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At Months 24, 48, 57 and 72
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Number of Subjects With Persistent Cervical Infection (6-month+ Definition) With Any Oncogenic HPV Type
Time Frame: At Months 24, 48, 57 and 72
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Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination.
Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
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At Months 24, 48, 57 and 72
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Number of Subjects With Persistent Cervical Infection (12-month+ Definition) With Any Oncogenic HPV Type
Time Frame: At Months 24,48, 57 and 72
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Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination.
Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
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At Months 24,48, 57 and 72
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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
Time Frame: At Months 24, 48, 57 and 72
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Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
US).
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At Months 24, 48, 57 and 72
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Number of Subjects With Any Cytological Abnormality Including Atypical Squamous Cells of Undetermined Significance (ASC-US+) Associated With Any Oncogenic HPV Type
Time Frame: At Months 24, 48, 57 and 72
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Cytological abnormalities = atypical squamous cells of undetermined significance (ASC-US).
Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination.
Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
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At Months 24, 48, 57 and 72
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Number of Subjects With Histopathologically-confirmed CIN1+ Associated With HPV-16 and/or HPV-18 Cervical Infection
Time Frame: At Months 24, 48, 57 and 72
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CIN1+ = CIN grades 1, 2, and3, low-grade cervical glandular intraepithelial neoplasia (LCGIN), high grade cervical glandular intraepithelial neoplasia (HCGIN), adenocarcinoma in-situ (AIS) or invasive cervical cancer.
DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
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At Months 24, 48, 57 and 72
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Number of Subjects With Histopathologically-confirmed CIN2+ Associated With HPV-16 and/or HPV-18 Cervical Infection
Time Frame: At Months 24, 48, 57 and 72
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CIN2+ = CIN grades 2 and 3, LCGIN, HCGIN, AIS or invasive cervical cancer.
DNA- and sero-: subjects HPV DNA negative at Months 0 and 6 by PCR and seronegative at Month 0 for the corresponding HPV-type by Enzyme-linked Immunosorbent Assay (ELISA) Overall: subjects DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
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At Months 24, 48, 57 and 72
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Number of Subjects With Histopathologically-confirmed CIN1+ Associated With Cervical Infection With Any Oncogenic HPV Type
Time Frame: At Months 24, 48, 57 and 72
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CIN1+ = CIN grades 1, 2 and 3, LCGIN, HCGIN, AIS or invasive cervical cancer.
Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination.
Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
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At Months 24, 48, 57 and 72
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Number of Subjects With Histopathologically-confirmed CIN2+ Associated With Cervical Infection With Any Oncogenic HPV Type
Time Frame: At Months 24, 48, 57 and 72
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CIN2+ = CIN grades 2 and 3, LCGIN, HCGIN, AIS or invasive cervical cancer.
Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68 individually or in combination.
Subjects were HPV DNA- at Months 0 and 6 for the corresponding HPV-type, regardless of initial serostatus.
HRW-HPV=All high-risk (oncogenic) HPV types excluding HPV-16 and HPV-18 HR-HPV=High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.
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At Months 24, 48, 57 and 72
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Number of Subjects With Any and Severe (Grade 3) Solicited Local Symptoms
Time Frame: Within 7 days (Days 0-6) after vaccination
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Solicited local symptoms assessed were pain, redness and swelling.
Any = solicited local symptom reported irrespective of intensity grade, Grade 3 Pain = pain that prevented normal activity, Grade 3 Swelling or Redness = swelling or redness above (>) 50 millimeter (mm).
All local symptoms were considered as related to the study vaccination.
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Within 7 days (Days 0-6) after vaccination
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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
Time Frame: Within 7 days (Days 0-6) after vaccination
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Solicited local symptoms assessed were pain, redness and swelling.
Any = solicited local symptom reported irrespective of intensity grade Grade 3 Pain = pain that prevented normal activity Grade 3 Swelling or Redness = swelling/redness above (>) 50 millimeter (mm).
All local symptoms were considered as related to the study vaccination.
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Within 7 days (Days 0-6) after vaccination
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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
Time Frame: Within 7 days (Days 0-6) after vaccination
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Solicited local symptoms assessed were pain, redness and swelling.
Any = solicited local symptom reported irrespective of intensity grade Grade 3 Pain = pain that prevented normal activity, Grade 3 Swelling or Redness = swelling/redness above (>) 50 millimeter (mm).
All local symptoms were considered as related to the study vaccination.
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Within 7 days (Days 0-6) after vaccination
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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
Time Frame: Within 7 days (Days 0-6) after vaccination
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Solicited local symptoms assessed were pain, redness and swelling.
Any = solicited local symptom reported irrespective of intensity grade, Grade 3 Redness, Swelling = redness/swelling above 50 millimeter All local symptoms were considered as related to the study vaccination
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Within 7 days (Days 0-6) after vaccination
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Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Solicited General Symptoms.
Time Frame: Within 7 days (Days 0-6) after vaccination
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Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, fever (= axillary temperature above 37.0 degrees Celsius) and urticaria.
Any = any solicited general symptom reported irrespective of intensity grade and relationship to vaccination, Related = symptoms assessed by the investigator as causally related to study vaccination, Grade 3 symptoms = prevented normal activity, Grade 3 urticaria = distributed on at least 4 body areas.
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Within 7 days (Days 0-6) after vaccination
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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
Time Frame: Within 7 days (Days 0-6) after vaccination
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Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, fever (= axillary temperature above 37.0°C) and urticaria.
Any = any solicited general symptom reported irrespective of intensity grade and relationship to vaccination Related = symptoms assessed by the investigator as causally related to study vaccination Grade 3 symptoms = symptoms that prevented normal activity Grade 3 urticaria = urticaria distributed on at least 4 body areas.
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Within 7 days (Days 0-6) after vaccination
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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
Time Frame: Within 7 days (Days 0-6) after vaccination
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Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, fever (= axillary temperature above 37.0°C) and urticaria.
Any = any solicited general symptom reported irrespective of intensity grade and relationship to vaccination Related = symptoms assessed by the investigator as causally related to study vaccination Grade 3 symptoms = symptoms that prevented normal activity Grade 3 urticaria = urticaria distributed on at least 4 body areas
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Within 7 days (Days 0-6) after vaccination
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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
Time Frame: Within 7 days (Days 0-6) after vaccination
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Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, fever (= axillary temperature above 37.0°C) and urticaria.
Any = any solicited general symptom reported irrespective of intensity grade and relationship to vaccination Related = symptoms assessed by the investigator as causally related to study vaccination Grade 3 symptoms = symptoms that prevented normal activity Grade 3 urticaria = urticaria distributed on at least 4 body areas
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Within 7 days (Days 0-6) after vaccination
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Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Unsolicited Adverse Events (AEs)
Time Frame: Within Days 0-29 after vaccination
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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.
Related = event assessed by the investigator as causally related to study vaccination Grade 3 = event that prevented normal activity
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Within Days 0-29 after vaccination
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Number of Subjects With Unsolicited Adverse Events for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline
Time Frame: Within Days 0-29 after vaccination
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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.
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Within Days 0-29 after vaccination
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Number of Subjects With Unsolicited Adverse Events for Subjects Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline
Time Frame: Within Days 0-29 after vaccination
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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
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Within Days 0-29 after vaccination
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Number of Subjects With Unsolicited Adverse Events for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline
Time Frame: Within Days 0-29 after vaccination
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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.
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Within Days 0-29 after vaccination
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Number of Subjects With Serious Adverse Events (SAEs)
Time Frame: From Day 0 to Month 72
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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.
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From Day 0 to Month 72
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Number of Subjects With Medically Significant Conditions (MSC) Regardless of Causal Relationship to Vaccination and Intensity
Time Frame: From Day 0 to Month 72
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Medically significant conditions 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 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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From Day 0 to Month 72
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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
Time Frame: From Day 0 to Month 72
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Medically significant conditions 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 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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From Day 0 to Month 72
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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
Time Frame: From Day 0 to Month 72
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Medically significant conditions 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 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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From Day 0 to Month 72
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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
Time Frame: From Day 0 to Month 72
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Medically significant conditions 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 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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From Day 0 to Month 72
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Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies
Time Frame: From Day 0 to Month 72
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Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant CA, Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up and Pregnancy ongoing.
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From Day 0 to Month 72
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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
Time Frame: From Day 0 to Month 72
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Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant CA, Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up, Pregnancy ongoing and MIssing.
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From Day 0 to Month 72
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Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline
Time Frame: From Day 0 to Month 72
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Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant CA, Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up, Pregnancy ongoing and Missing.
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From Day 0 to Month 72
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Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline
Time Frame: From Day 0 to Month 72
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Outcomes of pregnancies were Live infant NO apparent congenital anomaly (ACA), Live infant CA, Elective termination NO ACA, Elective termination CA, Ectopic pregnancy, Spontaneous abortion NO ACA, Stillbirth NO ACA, Stillbirth CA, Lost to follow up and Pregnancy ongoing.
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From Day 0 to Month 72
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Number of Subjects With HPV-16 Antibody Concentration Equal to or Above the Assay Cut-off Value, by Pre-vaccination Status
Time Frame: at Months 0 (PRE), 7, 12, 24, 36, 48 and 72
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HPV-16 assay cut-off value was defined as greater than or equal to (≥) 8 ELISA units per millilitre (EL.U/mL) at PRE vaccination, Month 7, 12 and 24 and ≥ 19 EL.U/mL at Month 36, 48 and 72.
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 ≥ 8 EL.U/mL prior to vaccination.
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at Months 0 (PRE), 7, 12, 24, 36, 48 and 72
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Number of Subjects With HPV-18 Antibody Concentration Equal to or Above the Assay Cut-off Value, by Pre-vaccination Status
Time Frame: at Months 0 (PRE), 7, 12, 24, 36, 48 and 72
|
HPV-18 assay cut-off value was defined as ≥ 7 EL.U/mL at PRE vaccination, Month 7, 12 and 24 and ≥ 18 EL.U/mL at Month 36, 48 and 72.
Seronegative (Sero-) subjects are subjects who had an antibody concentration below 7 EL.U/mL and 18 EL.U/mL prior to vaccination.
Seropositive (Sero+) subjects are subjects who had an antibody concentration ≥ 7 EL.U/mL and 18 EL.U/mL prior to vaccination.
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at Months 0 (PRE), 7, 12, 24, 36, 48 and 72
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Geometric Mean Titers for HPV-16/HPV-18 Antibodies, by Pre-vaccination Status
Time Frame: at Months 0 (PRE), 7, 12, 24, 36, 48 and 72
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Titers were expressed as geometric mean titers calculated on all subjects, HPV-16 assay cut-off value was defined as greater than or equal to 8 EL.U/mL at Months 0, 7, 12 and 24 and greater than or equal to 19 EL.U/mL at Months 36, 48 and 72.
HPV-18 assay cut-off value was defined as ≥ 7 EL.U/mL at Month 0, 7, 12 and 24 and ≥ 18 EL.U/mL at Months 36, 48 and 72.
Seronegative (Sero-) subjects are subjects who had an antibody concentration below the assay cut-off value prior to vaccination.
Seropositive (Sero+) subjects are subjects who had an antibody concentration ≥ the assay cut-off value prior to vaccination.
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at Months 0 (PRE), 7, 12, 24, 36, 48 and 72
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 22, 2008
Primary Completion (Actual)
September 6, 2011
Study Completion (Actual)
February 28, 2016
Study Registration Dates
First Submitted
October 23, 2008
First Submitted That Met QC Criteria
October 23, 2008
First Posted (Estimate)
October 24, 2008
Study Record Updates
Last Update Posted (Actual)
June 10, 2019
Last Update Submitted That Met QC Criteria
May 3, 2019
Last Verified
May 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 107638
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
IPD is available via the Clinical Study Data Request site (click on the link provided below).
IPD Sharing Time Frame
IPD is available via the Clinical Study Data Request site (click on the link provided below)
IPD Sharing Access Criteria
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 Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Study Data/Documents
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Dataset Specification
Information identifier: 107638Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Clinical Study Report
Information identifier: 107638Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Study Protocol
Information identifier: 107638Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Annotated Case Report Form
Information identifier: 107638Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Statistical Analysis Plan
Information identifier: 107638Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Informed Consent Form
Information identifier: 107638Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Individual Participant Data Set
Information identifier: 107638Information comments: For additional information about this study please refer to the GSK Clinical Study Register
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.