Infections, Papillomavirus
Conditions
Keywords
medically significant conditions, cervical neoplasia, serious adverse events (SAEs), HPV vaccine
Brief summary
This extension study is designed to assess the safety of GSK Biological's HPV vaccine GSK580299 in female subjects who took part in the primary study NCT00294047 and received the control vaccine in countries for which the licensed GSK HPV vaccine is not indicated for the subject's age group (26 years and older). This study is thus conducted to enable all women who received the control placebo in the primary NCT00294047 study to receive the GSK580299 vaccine.
Detailed description
This Protocol Posting has been updated following Protocol Amendment 1, December 2010, leading to the update of 1 of the primary outcome measures and following Protocol Amendment 2, January 2011, leading to the removal of one of the exclusion criteria.
Interventions
BIOLOGICALGSK580299 (Cervarix)
3-dose schedule intramuscularly vaccination
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
26 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes can and will comply with the requirements of the protocol * A subject previously enrolled in the study NCT00294047, who received the control vaccine, and who cannot receive the GSK580299 vaccine because the subject is above the age for which the vaccine is licensed. * Written informed consent obtained from the subject * Free of obvious health problems 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. * 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
* Pregnant or breastfeeding. * A women planning to become pregnant, likely 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. * Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period. * Previous vaccination against HPV or planned administration of another HPV vaccine during the study other than that foreseen in the protocol. * 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 (i.e., Day 0-29) of each dose of vaccine, with the exception of administration of routine meningococcal, hepatitis B, hepatitis A, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccine up to 8 days before each dose of study vaccine. Enrolment will be deferred until the subject is outside of specified window. * 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 product. NOTE: Subjects enrolled in this study may also be eligible for a four-year gynaecological follow-up of the HPV-015 study, in which no investigational product will be administered. Subjects will be invited to the gynaecological follow-up study if either of the following applies: * if they test positive for oncogenic HPV infection, but display normal cervical cytology at their concluding HPV-015 study end visit; * if they are pregnant so that no cervical sample can be taken at their concluding HPV-015 study end visit; * Previous administration of any components of the vaccine. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * Cancer or autoimmune disease under treatment. * Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period. * History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine * History of any neurological disorders or seizures. * Acute disease and/or fever at the time of enrolment. * Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Serious Adverse Events | Throughout the study (from Month 0 to Month 12) | Serious adverse events (SAEs) assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as the occurrence of any SAE regardless of intensity grade or relation to vaccination. Grade 3 SAE = SAE which prevented normal, everyday activities (in adults/adolescents, such an SAE, for example, prevented attendance at work/school and necessitated the administration of corrective therapy). Related SAE = SAE assessed by the investigator as causally related to the study vaccination. |
| Number of Subjects Reporting Medically Significant Conditions (MSCs) and Potential Immune-mediated Diseases (pIMDs) | Throughout the study (from Month 0 to Month 12) | Medically significant conditions (MSCs) are defined as: AEs prompting emergency room or physician visits that were not related to common diseases, or not related to routine visits for physical examination or vaccination; SAEs that were not related to common diseases. Common diseases include: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury. Potential immune-mediated diseases (pIMDs) are a subset of medically significant conditions that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. Any was defined as the occurrence of any MSC or pIMD regardless of intensity grade or relation to vaccination. Grade 3 MSC or pIMD = a MSC or pIMD which prevented normal, everyday activities. Related MSC or pIMD = a MSC or pIMD assessed by the investigator as related to the vaccination. |
| Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Throughout the study (from Month 0 to Month 12) | Live infant NO apparent congenital anomaly; Live infant congenital anomaly; Premature live infant NO apparent congenital anomaly; Premature live infant congenital anomaly; Elective termination NO apparent congenital anomaly; Elective termination congenital anomaly; Therapeutic abortion; Ectopic pregnancy; Spontaneous abortion NO apparent congenital anomaly; Spontaneous abortion congenital anomaly; Stillbirth NO apparent congenital anomaly; Stillbirth congenital anomaly; Molar pregnancy; Pregnancy ongoing; Lost to follow up. |
Countries
Australia, Portugal, Russia, Singapore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HPV Vaccine Healthy female subjects aged 26 years and above, who received control vaccine in the primary study NCT00294047, were administrated 3 intramuscular injections of Cervarix vaccine into the deltoid of the non-dominant arm, according to a 0, 1, 6-month schedule in the current study. | 199 |
| Total | 199 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | HPV Vaccine |
|---|---|
| Age, Continuous | 46.9 Years STANDARD_DEVIATION 7.2 |
| Race/Ethnicity, Customized Geographic ancestry African Heritage/African American | 1 Participants |
| Race/Ethnicity, Customized Geographic ancestry Asian - Central/South Asian Heritage | 2 Participants |
| Race/Ethnicity, Customized Geographic ancestry Asian - East Asian Heritage | 2 Participants |
| Race/Ethnicity, Customized Geographic ancestry Asian - South East Asian Heritage | 78 Participants |
| Race/Ethnicity, Customized Geographic ancestry White - Caucasian/European Heritage | 116 Participants |
| Sex: Female, Male Female | 199 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 199 |
| other Total, other adverse events | 0 / 199 |
| serious Total, serious adverse events | 6 / 199 |
Outcome results
Primary
Number of Subjects Reporting Medically Significant Conditions (MSCs) and Potential Immune-mediated Diseases (pIMDs)
Medically significant conditions (MSCs) are defined as: AEs prompting emergency room or physician visits that were not related to common diseases, or not related to routine visits for physical examination or vaccination; SAEs that were not related to common diseases. Common diseases include: upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervicovaginal yeast infections, menstrual cycle abnormalities and injury. Potential immune-mediated diseases (pIMDs) are a subset of medically significant conditions that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. Any was defined as the occurrence of any MSC or pIMD regardless of intensity grade or relation to vaccination. Grade 3 MSC or pIMD = a MSC or pIMD which prevented normal, everyday activities. Related MSC or pIMD = a MSC or pIMD assessed by the investigator as related to the vaccination.
Time frame: Throughout the study (from Month 0 to Month 12)
Population: The analysis was based on the Total Vaccinated cohort, which included all subjects with the study vaccine administered.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HPV Vaccine | Number of Subjects Reporting Medically Significant Conditions (MSCs) and Potential Immune-mediated Diseases (pIMDs) | Any MSCs | 16 Participants |
| HPV Vaccine | Number of Subjects Reporting Medically Significant Conditions (MSCs) and Potential Immune-mediated Diseases (pIMDs) | Grade 3 MSCs | 2 Participants |
| HPV Vaccine | Number of Subjects Reporting Medically Significant Conditions (MSCs) and Potential Immune-mediated Diseases (pIMDs) | Related MSCs | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Medically Significant Conditions (MSCs) and Potential Immune-mediated Diseases (pIMDs) | Any pIMDs | 1 Participants |
| HPV Vaccine | Number of Subjects Reporting Medically Significant Conditions (MSCs) and Potential Immune-mediated Diseases (pIMDs) | Grade 3 pIMDs | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Medically Significant Conditions (MSCs) and Potential Immune-mediated Diseases (pIMDs) | Related pIMDs | 0 Participants |
Primary
Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies
Live infant NO apparent congenital anomaly; Live infant congenital anomaly; Premature live infant NO apparent congenital anomaly; Premature live infant congenital anomaly; Elective termination NO apparent congenital anomaly; Elective termination congenital anomaly; Therapeutic abortion; Ectopic pregnancy; Spontaneous abortion NO apparent congenital anomaly; Spontaneous abortion congenital anomaly; Stillbirth NO apparent congenital anomaly; Stillbirth congenital anomaly; Molar pregnancy; Pregnancy ongoing; Lost to follow up.
Time frame: Throughout the study (from Month 0 to Month 12)
Population: The analysis was based on the Total Vaccinated cohort, which included all subjects with the study vaccine administered and who reported any pregnancies and outcomes of reported pregnancies.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Premature live infant congenital anomaly | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Elective termination NO apparent congen. anomaly | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Elective termination congenital anomaly | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Therapeutic abortion | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Ectopic pregnancy | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Spontaneous abortion NO apparent congen. anomaly | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Spontaneous abortion congenital anomaly | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Stillbirth NO apparent congenital anomaly | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Stillbirth congenital anomaly | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Molar pregnancy | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Pregnancy ongoing | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Lost to follow up | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Live infant NO apparent congenital anomaly | 1 Participants |
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Live infant congenital anomaly | 0 Participants |
| HPV Vaccine | Number of Subjects Reporting Pregnancies and Outcome of Reported Pregnancies | Premature live infant NO apparent congen. anomaly | 0 Participants |
Primary
Number of Subjects Reporting Serious Adverse Events
Serious adverse events (SAEs) assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as the occurrence of any SAE regardless of intensity grade or relation to vaccination. Grade 3 SAE = SAE which prevented normal, everyday activities (in adults/adolescents, such an SAE, for example, prevented attendance at work/school and necessitated the administration of corrective therapy). Related SAE = SAE assessed by the investigator as causally related to the study vaccination.
Time frame: Throughout the study (from Month 0 to Month 12)
Population: The analysis was based on the Total Vaccinated cohort, which included all subjects with the study vaccine administered.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HPV Vaccine | Number of Subjects Reporting Serious Adverse Events | Any SAE(s) | 6 Participants |
| HPV Vaccine | Number of Subjects Reporting Serious Adverse Events | Grade 3 SAE(s) | 2 Participants |
| HPV Vaccine | Number of Subjects Reporting Serious Adverse Events | Related SAE(s) | 0 Participants |