Efficacy, Immunogenicity and Safety of GlaxoSmithKline Biologicals' HPV GSK 580299 Vaccine in Healthy Chinese Female Subjects
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 6,081
- Locations
- 4
- Primary Endpoint
- 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
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 25 Years (Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
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.
Outcomes
Primary Outcomes
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
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.
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
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.
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
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.
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
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.
Secondary Outcomes
- Number of Subjects With Incident Cervical Infection With HPV-16 and/or HPV-18(At Months 24,48, 57 and 72)
- Number of Subjects With Persistent Cervical Infection (12-month+ Definition) With Any Oncogenic HPV Type(At Months 24,48, 57 and 72)
- Number of Subjects With Persistent Cervical Infection (6-month+ Definition) With HPV-16 and/or HPV-18(At Months 24, 48, 57 and 72)
- Number of Subjects With Persistent Cervical Infection (12-month+ Definition) With HPV-16 and/or HPV-18(At Months 24, 48, 57 and 72)
- Number of Subjects With Incident Cervical Infection With Any Oncogenic HPV Type(At Months 24, 48, 57 and 72)
- Number of Subjects With Persistent Cervical Infection (6-month+ Definition) With Any Oncogenic HPV Type(At Months 24, 48, 57 and 72)
- Number of Subjects With Histopathologically-confirmed CIN1+ Associated With Cervical Infection With Any Oncogenic HPV Type(At Months 24, 48, 57 and 72)
- Number of Subjects With Any Cytological Abnormality Including Atypical Squamous Cells of Undetermined Significance (ASC-US+) Associated With Any Oncogenic HPV Type(At Months 24, 48, 57 and 72)
- 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(At Months 24, 48, 57 and 72)
- Number of Subjects With Histopathologically-confirmed CIN1+ Associated With HPV-16 and/or HPV-18 Cervical Infection(At Months 24, 48, 57 and 72)
- Number of Subjects With Histopathologically-confirmed CIN2+ Associated With HPV-16 and/or HPV-18 Cervical Infection(At Months 24, 48, 57 and 72)
- Number of Subjects With Histopathologically-confirmed CIN2+ Associated With Cervical Infection With Any Oncogenic HPV Type(At Months 24, 48, 57 and 72)
- 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(Within 7 days (Days 0-6) after vaccination)
- Number of Subjects With Any and Severe (Grade 3) Solicited Local Symptoms(Within 7 days (Days 0-6) after vaccination)
- 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(Within 7 days (Days 0-6) after vaccination)
- 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(Within 7 days (Days 0-6) after vaccination)
- 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(Within 7 days (Days 0-6) after vaccination)
- Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Solicited General Symptoms.(Within 7 days (Days 0-6) after vaccination)
- Number of Subjects With Unsolicited Adverse Events for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline(Within Days 0-29 after vaccination)
- Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline(From Day 0 to Month 72)
- Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies for Subjects DNA Positive for Either HPV-16 or HPV-18 at Baseline(From Day 0 to Month 72)
- 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(Within 7 days (Days 0-6) after vaccination)
- Number of Subjects With Any, Severe (Grade 3) and Causally Related to Vaccination Unsolicited Adverse Events (AEs)(Within Days 0-29 after vaccination)
- Number of Subjects With Unsolicited Adverse Events for Subjects Seropositive and/or DNA Positive for Either HPV-16 or HPV-18 at Baseline(Within Days 0-29 after vaccination)
- 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(Within 7 days (Days 0-6) after vaccination)
- Number of Subjects With Unsolicited Adverse Events for Subjects Seronegative and DNA Negative for Both HPV-16 and HPV-18 at Baseline(Within Days 0-29 after vaccination)
- Number of Subjects With Serious Adverse Events (SAEs)(From Day 0 to Month 72)
- Number of Subjects With Medically Significant Conditions (MSC) Regardless of Causal Relationship to Vaccination and Intensity(From Day 0 to Month 72)
- 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(From Day 0 to Month 72)
- 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(From Day 0 to Month 72)
- 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(From Day 0 to Month 72)
- Number of Subjects With Pregnancies and Outcomes of Reported Pregnancies(From Day 0 to Month 72)
- 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(From Day 0 to Month 72)
- Number of Subjects With HPV-16 Antibody Concentration Equal to or Above the Assay Cut-off Value, by Pre-vaccination Status(at Months 0 (PRE), 7, 12, 24, 36, 48 and 72)
- Number of Subjects With HPV-18 Antibody Concentration Equal to or Above the Assay Cut-off Value, by Pre-vaccination Status(at Months 0 (PRE), 7, 12, 24, 36, 48 and 72)
- Geometric Mean Titers for HPV-16/HPV-18 Antibodies, by Pre-vaccination Status(at Months 0 (PRE), 7, 12, 24, 36, 48 and 72)