Safety and Protective Effect Study of GSK Biologicals' Human Papillomavirus (Types 16, 18) Vaccine, Adsorbed (GSK580299) in Healthy Female Subjects From the HPV-039 Study

Study Overview
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Brief Summary
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This study was designed to enable all subjects who received placebo in the HPV-039 study (NCT00779766), to also receive GSK Biologicals' Human Papillomavirus (Types 16, 18) Vaccine, Adsorbed. Safety data in terms of serious adverse events (SAEs), any adverse events (AEs)/SAEs leading to premature discontinuation of the study, potential immune mediated diseases (pIMDs) and pregnancies (and their outcomes) were collected during the study period. In addition, this study assessed the long term protective effect of the vaccine, in an exploratory manner, in terms of rates of HPV-related (vaccine type) incident cervical infection up to approximately 10 years after vaccination in subjects who participated in HPV-039 study (NCT00779766).

Detailed Description
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Treatment allocation depended on the randomization in the previous study i.e. only the subjects from the control group of HPV-039 study received HPV vaccination in the current study. Subjects who previously received the Human Papillomavirus (Types 16, 18) Vaccine, Adsorbed in HPV-039 study did not receive vaccination in this study.

Official Title
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Safety and Protective Effect Study of GSK Biologicals' Human Papillomavirus (Types 16, 18) Vaccine, Adsorbed (GSK580299) in Healthy Female Subjects From the HPV-039 Study

Conditions
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Cervical Intraepithelial Neoplasia

Intervention / Treatment
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* Biological: HPV (Types 16, 18) Vaccine, Adsorbed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol. Written informed consent obtained from the subject prior to performing any study specific procedure. Subjects previously enrolled in the HPV-039 study. Subjects with negative pregnancy test at Visit 1. Additional inclusion criteria for subjects of HPV group undergoing vaccination ONLY: Healthy subjects as established by medical history and clinical examination before entering into the study. Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. Female subjects of childbearing potential may be enrolled in the study, if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series. Exclusion Criteria: Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device). Previous vaccination against HPV outside of study HPV-039. Additional exclusion criteria for subjects of HPV group undergoing vaccination ONLY: Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the first dose of study vaccine, or planned use during the study period. Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone. Inhaled and topical steroids are allowed. Planned administration/administration of a vaccine/product not foreseen by the study protocol in the period starting 30 days before and after each dose of vaccine administration, with the exception of administration of routine vaccines e.g. meningococcal, hepatitis B, hepatitis A, inactivated influenza up to eight days before and after each dose of study vaccine. Enrolment will be deferred until the subject is outside of the specified window. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. Previous administration of MPL or AS04 adjuvant. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Cancer or autoimmune disease under treatment. Hypersensitivity to latex. Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥37.0°C. The preferred location for measuring temperature in this study will be the axilla. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. Pregnant or breastfeeding. Subjects must be at least three months post-pregnancy and not breastfeeding to enter the study. Females planning to become pregnant or planning to discontinue contraceptive precautions during the vaccination phase of the study, i.e. up to two months after the last vaccine dose.

Ages Eligible for Study
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Minimum Age: 26 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Vacc-039 Group<br>Healthy Chinese female subjects, above 26 years of age at study entry, who previously received HPV vaccine in HPV-039 study (NCT00779766), underwent cervical sample collection and didn't receive any vaccine in the current study. | |
| Experimental: Vacc-092 Group<br>Healthy Chinese female subjects, above 26 years of age at study entry, who previously received placebo (control group) in HPV-039 study (NCT00779766), were intended to receive HPV vaccine in the current study and were to provide cervical samples before HPV vaccination. | Biological: HPV (Types 16, 18) Vaccine, Adsorbed<br>* Three doses of Human Papillomavirus (Types 16, 18) Vaccine, Adsorbed administered intramuscularly in the deltoid region of the upper arm, according to a 0, 1, 6-month schedule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Serious Adverse Events (SAEs) Related to Study Vaccine in Vacc-092 Group | SAEs assessed include any untoward medical occurrence that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Related SAEs are those SAEs assessed by the investigator as related to vaccination in the study. | During the entire study period (Day 1-Month 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Potential Immune Mediated Diseases (pIMDs) in Vacc-092 Group | pIMDS are a subset of adverse events (AEs) that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which might or might not have an autoimmune aetiology. | During the entire study period (Day 1-Month 12) | 
| Number of Pregnant Subjects Reported With Outcomes of Pregnancy in Vacc-092 Group | Pregnancy is the term used to describe the period in which a fetus develops inside a woman's womb or uterus. The subjects with confirmed pregnancies were followed up to determine the outcomes of the reported pregnancies. Outcomes of the reported pregnancies were: Live infant no apparent Congenital Anomaly (CA), Live infant CA, Elective termination no apparent CA, Elective termination CA, Spontaneous abortion no apparent CA, Spontaneous abortion CA, Stillbirth no apparent CA, Stillbirth CA, Ectopic pregnancy, Molar pregnancy, Lost to follow-up & Pregnancy ongoing. | During the entire study period (Day 1-Month 12) | 
| Number of Subjects With SAEs in Vacc-092 Group | SAEs assessed include any untoward medical occurrence that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. | During the entire study period (Day 1-Month 12) | 
| Number of Subjects With Any Adverse Events or Serious Adverse Events (AE/SAE) Leading to Premature Discontinuation From the Study in Vacc-092 Group | AEs assessed include any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse. SAEs assessed include any untoward medical occurrence that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any is defined as the occurrence of any unsolicited AE/SAE regardless of intensity grade or relation to vaccination. | During the entire study period (Day 1-Month 12) | 
| Number of Subjects With SAEs Related to Study Participation in All Study Groups | SAEs assessed include any untoward medical occurrence that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Related SAEs are those SAEs assessed by the investigator as activities related to study participation and not by study vaccine (e.g. SAEs due to invasive tests). | During the entire study period (Day 1-Month 12) | 
| Incidence Rates of Incident Cervical Infection With HPV-16 and/or HPV-18 (by PCR) in HPV DNA Negative and Seronegative Subjects at Baseline in All Study Groups | The incidence rate (n/T) of incident cervical infection with HPV-16 and/or HPV-18 (per 100 Person-years rate) was calculated as the number of subjects reporting at least one event (n) in a group, over the sum of follow-up period expressed in years (T) in the same group, and multiplied by 100. Cervical infection caused by HPV Types 16 and 18 was assessed by detecting HPV DNA using Polymerase Chain Reaction (PCR). For single HPV type: Subjects DNA negative at Month 0 and seronegative at Month 0 for the corresponding HPV type in study HPV 039 (NCT00779766). For combined HPV types: Subjects DNA negative at Month 0 and seronegative at Month 0 for at least one HPV type (subjects were in the analysis of at least one single type) in study HPV 039 (NCT00779766). | From Month 0 in HPV-039 (NCT00779766) study [at the Day after Dose 1 (out of 3 doses administered in HPV-039)] until Month 120 (corresponding to Day 1 in the current study) | 
| Incidence Rates of Incident Cervical Infection With HPV-16 and/or HPV-18 (by PCR) in HPV DNA Negative Subjects at Baseline, Regardless of Initial Serostatus in All Study Groups | The incidence rate (n/T) of incident cervical infection with HPV-16 and/or HPV-18 (per 100 Person-years rate) was calculated as the number of subjects reporting at least one event (n) in a group, over the sum of follow-up period expressed in years (T) in the same group, and multiplied by 100. Cervical infection caused by HPV Types 16 and 18 was assessed by detecting HPV DNA using Polymerase Chain Reaction (PCR). For single HPV type: Subjects DNA negative at Month 0 for the corresponding HPV type in study HPV-039 (NCT00779766). For combined HPV types: Subjects DNA negative at Month 0 for at least one HPV type (subjects were in the analysis of at least one single type) in study HPV-039 (NCT00779766). | From Month 0 in HPV-039 (NCT00779766) study [at the Day after Dose 1 (out of 3 doses administered in HPV-039)] until Month 120 (corresponding to Day 1 in the current study) | 
| Incidence Rates of Incident Cervical Infection With Any Oncogenic HPV Type or Combination of Oncogenic HPV Types in HPV DNA Negative Subjects at Baseline, Regardless of Initial Serostatus in All Study Groups | The IR (n/T) of incident cervical infection with any oncogenic HPV type or combination of oncogenic HPV types (per 100 Person-years rate) was calculated as the number of subjects reporting at least one event (n) in a group (assessed by detecting HPV DNA using PCR), over the sum of follow-up period expressed in years (T) in the same group, and multiplied by 100. Oncogenic HPV types assessed were HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66 and -68. HRW-HPV = High-risk (oncogenic) HPV types without HPV-16 or HPV-18: HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. HR-HPV = High-risk (oncogenic) HPV types: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. For single type: Subjects DNA negative at Month 0 for the corresponding HPV type in NCT00779766 study. For combined types: Subjects DNA negative at Month 0 for at least one HPV type (subjects were in the analysis of at least 1 single type) in NCT00779766 study. | From Month 0 in HPV-039 (NCT00779766) study [at the Day after Dose 1 (out of 3 doses administered in HPV-039)] until Month 120 (corresponding to Day 1 in the current study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adults, Human Papillomavirus (HPV), Cervical cancer, Safety