Infections, Papillomavirus
Conditions
Keywords
Serious adverse events (SAEs), HPV vaccine, Medically significant conditions, Cervical neoplasia
Brief summary
This extension study is designed to assess the safety of GSK Biological's human papillomavirus (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 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. For corticosteroids, this will mean prednisone greater than or equal to 20 mg/day, or equivalent. Inhaled and topical steroids are allowed * 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 Any, Grade 3 and Related Serious Adverse Events (SAEs) | During the entire study period (from Day 0 up to Month 12) | Assessed SAEs included medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were congenital anomalies/birth defects in the offspring of a study subject. Any SAE = occurrence of the SAE regardless of intensity grade. Grade 3 SAE = an SAE which prevented normal, everyday activities. Related SAE = an SAE assessed by the investigator as causally related to the study vaccination. |
| Number of Subjects Reporting Any, Grade 3 and Related Medically Significant Conditions (MSCs) | During the entire study period (from Day 0 up to Month 12) | Medically significant conditions were defined as: AEs prompting emergency room or physician visits that were not (1) related to common diseases, or (2) not related to routine visits for physical examination or vaccination, or as 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. Any MSC = occurrence of the MSC regardless of intensity grade. Grade 3 MSC = a MSC which prevented normal, everyday activities. Related MSC = MSC assessed by the investigator as related to the study vaccination. |
| Number of Subjects Reporting Any, Grade 3 and Related Potentially Immune-Mediated Diseases (pIMDs) | During the entire study period (from Day 0 up to Month 12) | pIMD(s) are a subset of medically significant conditions (MSCs) that included autoimmune diseases and other inflammatory and/or neurological disorders of interest which may or may not have had an autoimmune aetiology. Any pIMD = occurrence of the pIMD regardless of intensity grade. Grade 3 pIMD = a pIMD which prevented normal, everyday activities. Related pIMD = pIMD assessed by the investigator as related to the study vaccination. |
| Number of Subjects Reporting Pregnancies and Outcomes of the Reported Pregnancies | During the entire study period (from Day 0 up to Month 12) | Pregnancy is the term used to describe the period in which a fetus develops inside a woman's womb or uterus. In this study, the number of subjects with pregnancies was calculated. The subjects with confirmed pregnancies were followed up to determine the outcomes of the reported pregnancies. |
Countries
Canada, United States
Participant flow
Recruitment details
This study was conducted by multiple investigators at 28 centers in Canada and the United States.
Pre-assignment details
All subjects enrolled were vaccinated and included in the Total Vaccinated cohort (TVc).
Participants by arm
| Arm | Count |
|---|---|
| Cervarix Group Healthy female subjects who received control vaccine in the primary study HPV-015 (NCT00294047), were administered three doses of Cervarix vaccine intramuscularly, according to a 0,1,6-month schedule. | 137 |
| Total | 137 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Migrated/moved from study area | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Cervarix Group |
|---|---|
| Age, Continuous | 47.9 Years STANDARD_DEVIATION 7.2 |
| Race/Ethnicity, Customized Geographic Ancestry African Heritage/African American | 11 Participants |
| Race/Ethnicity, Customized Geographic Ancestry Asian - East Asian Heritage | 1 Participants |
| Race/Ethnicity, Customized Geographic Ancestry Asian - Japanese Heritage | 2 Participants |
| Race/Ethnicity, Customized Geographic Ancestry Cuban | 1 Participants |
| Race/Ethnicity, Customized Geographic Ancestry Native Canadian | 2 Participants |
| Race/Ethnicity, Customized Geographic Ancestry White - Arabic/North African Heritage | 1 Participants |
| Race/Ethnicity, Customized Geographic Ancestry White - Caucasian/European Heritage | 119 Participants |
| Sex: Female, Male Female | 137 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 137 |
| other Total, other adverse events | 24 / 137 |
| serious Total, serious adverse events | 1 / 137 |
Outcome results
Primary
Number of Subjects Reporting Any, Grade 3 and Related Medically Significant Conditions (MSCs)
Medically significant conditions were defined as: AEs prompting emergency room or physician visits that were not (1) related to common diseases, or (2) not related to routine visits for physical examination or vaccination, or as 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. Any MSC = occurrence of the MSC regardless of intensity grade. Grade 3 MSC = a MSC which prevented normal, everyday activities. Related MSC = MSC assessed by the investigator as related to the study vaccination.
Time frame: During the entire study period (from Day 0 up to Month 12)
Population: The analysis was performed on the Total Vaccinated cohort (TVc), which included all vaccinated subjects for whom safety data were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Medically Significant Conditions (MSCs) | Any MSC(s) | 24 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Medically Significant Conditions (MSCs) | Grade 3 MSC(s) | 2 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Medically Significant Conditions (MSCs) | Related MSC(s) | 1 Participants |
Primary
Number of Subjects Reporting Any, Grade 3 and Related Potentially Immune-Mediated Diseases (pIMDs)
pIMD(s) are a subset of medically significant conditions (MSCs) that included autoimmune diseases and other inflammatory and/or neurological disorders of interest which may or may not have had an autoimmune aetiology. Any pIMD = occurrence of the pIMD regardless of intensity grade. Grade 3 pIMD = a pIMD which prevented normal, everyday activities. Related pIMD = pIMD assessed by the investigator as related to the study vaccination.
Time frame: During the entire study period (from Day 0 up to Month 12)
Population: The analysis was performed on the Total Vaccinated cohort (TVc), which included all vaccinated subjects for whom safety data were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Potentially Immune-Mediated Diseases (pIMDs) | Any pIMD(s) | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Potentially Immune-Mediated Diseases (pIMDs) | Grade 3 pIMD(s) | 0 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Potentially Immune-Mediated Diseases (pIMDs) | Related pIMD(s) | 0 Participants |
Primary
Number of Subjects Reporting Any, Grade 3 and Related Serious Adverse Events (SAEs)
Assessed SAEs included medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were congenital anomalies/birth defects in the offspring of a study subject. Any SAE = occurrence of the SAE regardless of intensity grade. Grade 3 SAE = an SAE which prevented normal, everyday activities. Related SAE = an SAE assessed by the investigator as causally related to the study vaccination.
Time frame: During the entire study period (from Day 0 up to Month 12)
Population: The analysis was performed on the Total Vaccinated cohort (TVc), which included all vaccinated subjects for whom safety data were available.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Serious Adverse Events (SAEs) | Any SAE(s) | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Serious Adverse Events (SAEs) | Grade 3 SAE(s) | 1 Participants |
| Cervarix Group | Number of Subjects Reporting Any, Grade 3 and Related Serious Adverse Events (SAEs) | Related SAE(s) | 0 Participants |
Primary
Number of Subjects Reporting Pregnancies and Outcomes of the Reported Pregnancies
Pregnancy is the term used to describe the period in which a fetus develops inside a woman's womb or uterus. In this study, the number of subjects with pregnancies was calculated. The subjects with confirmed pregnancies were followed up to determine the outcomes of the reported pregnancies.
Time frame: During the entire study period (from Day 0 up to Month 12)
Population: The analysis was performed on the Total Vaccinated cohort (TVc), which included all vaccinated subjects for whom safety data were available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervarix Group | Number of Subjects Reporting Pregnancies and Outcomes of the Reported Pregnancies | 0 Participants |