Infections, Papillomavirus
Conditions
Keywords
papillomavirus, HPV vaccine, cervical cancer, HPV, human papillomavirus
Brief summary
This phase 3b study is designed to assess the safety of GlaxoSmithKline Biological's HPV vaccine GSK580299 in female subjects who took part in study 580299/008 and received the control vaccine (Hepatitis A vaccine).
Interventions
BIOLOGICALGSK Biological's HPV vaccine GSK580299 (Cervarix™)
All subjects will receive a 0.5 ml dose administered as an intramuscular injection, according to a 0, 1, 6-month schedule.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study * A subject previously enrolled in the primary study (NCT00122681), who received the active control hepatitis A vaccine, and who cannot receive commercially available HPV-16/18 L1 VLP AS04 vaccine because the vaccine has not yet been granted licensure in the subject's country or because the subject is above the age for which the vaccine is licensed. * Written informed consent must be obtained from the subject prior to enrolment. * A woman aged 18 years or older, at the time of the first vaccination in this study. * Healthy subjects as established by medical history and clinical examination before entering into the study. * Subjects must not be pregnant. Absence of pregnancy should be verified with a urine pregnancy test. * Subject must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series.
Exclusion criteria
* Pregnant or lactating female. Enrolment should be deferred until three months after pregnancy has been completed or after lactating has ceased. * A woman planning to become pregnant or likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive prevention during the study period and up to two months after the last vaccine dose. * Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period and the extended safety follow-up period. * 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 non-investigational product (pharmaceutical product or device). * Previous vaccination against HPV or planned administration of another HPV vaccine during the study other than that foreseen by protocol. * 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. 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 is allowed. Enrolment will be deferred until the subject is outside of specified window. * Previous administration of components of the investigational vaccine. * History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccine. * Hypersensitivity to latex. * Acute or chronic, clinically significant pulmonary, cardiovascular, neurologic, haematological, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests, which in the opinion of the investigator precludes administration of the study vaccine. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * Cancer or autoimmune disease under treatment. * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. * Acute disease at the time of enrolment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs) | Throughout the study (up to Month 12) | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Any = Occurrence of any SAE regardless of intensity grade or relation to vaccination. Grade 3 = SAE which prevented normal, everyday activities. Related = SAE assessed by the investigator as related to the vaccination. |
| Number of Subjects With Any, Grade 3 and Related Medically Significant Conditions (MSCs) | Throughout the study (up to Month 12) | MSCs = Adverse events (AEs) prompting emergency room/physician visits not related to common diseases or routine visits for physical examination/vaccination, or SAEs 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. Any = Occurrence of any MSC regardless of intensity grade or relation to vaccination. Grade 3 = MSC which prevented normal, everyday activities. Related = MSC assessed by the investigator as related to the vaccination. |
| Number of Subjects With Pregnancies and Pregnancy Outcomes. | Throughout the study (up to Month 12) | — |
Countries
Canada, United States
Participant flow
Pre-assignment details
Subjects in this study come from the primary study (NCT00122681) where they were included in the control group and received Hepatitis A vaccination. The number of subjects that started the study included only those subjects with the vaccine dose administered.
Participants by arm
| Arm | Count |
|---|---|
| Cervarix Group Female subjects who previously received the active control i.e. Hepatitis A vaccine in the primary study (NCT00122681) and who received the Cervarix vaccine in the current study. The Cervarix vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm according to a 0, 1 and 6 months schedule. | 344 |
| Total | 344 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 38 |
| Overall Study | Pregnancy | 3 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Cervarix Group |
|---|---|
| Age, Continuous | 25.4 Years STANDARD_DEVIATION 2.81 |
| Sex: Female, Male Female | 344 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 344 |
| serious Total, serious adverse events | 8 / 344 |
Outcome results
Primary
Number of Subjects With Any, Grade 3 and Related Medically Significant Conditions (MSCs)
MSCs = Adverse events (AEs) prompting emergency room/physician visits not related to common diseases or routine visits for physical examination/vaccination, or SAEs 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. Any = Occurrence of any MSC regardless of intensity grade or relation to vaccination. Grade 3 = MSC which prevented normal, everyday activities. Related = MSC assessed by the investigator as related to the vaccination.
Time frame: Throughout the study (up to Month 12)
Population: The analyses were performed on the Total Vaccinated cohort, which included all subjects who received at least one dose of Cervarix vaccine in this study, for whom data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Subjects With Any, Grade 3 and Related Medically Significant Conditions (MSCs) | Any MSCs | 32 Subjects |
| Cervarix Group | Number of Subjects With Any, Grade 3 and Related Medically Significant Conditions (MSCs) | Grade 3 MSCs | 9 Subjects |
| Cervarix Group | Number of Subjects With Any, Grade 3 and Related Medically Significant Conditions (MSCs) | Related MSCs | 0 Subjects |
Primary
Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Any = Occurrence of any SAE regardless of intensity grade or relation to vaccination. Grade 3 = SAE which prevented normal, everyday activities. Related = SAE assessed by the investigator as related to the vaccination.
Time frame: Throughout the study (up to Month 12)
Population: The analyses were performed on the Total Vaccinated cohort, which included all subjects who received at least one dose of Cervarix vaccine in this study, for whom data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs) | Grade 3 SAEs | 5 Subjects |
| Cervarix Group | Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs) | Related SAEs | 0 Subjects |
| Cervarix Group | Number of Subjects With Any, Grade 3 and Related Serious Adverse Events (SAEs) | Any SAEs | 8 Subjects |
Primary
Number of Subjects With Pregnancies and Pregnancy Outcomes.
Time frame: Throughout the study (up to Month 12)
Population: The analysis was based on pregnant subjects from the Total Vaccinated cohort, which included all subjects who received at least one dose of Cervarix vaccine in this study, for whom data were available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Live infant NO apparent congenital anomaly | 14 Subjects |
| Cervarix Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Elective termination NO apparent congenital anom. | 2 Subjects |
| Cervarix Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Spontaneous abortion NO apparent congenital anom. | 2 Subjects |
| Cervarix Group | Number of Subjects With Pregnancies and Pregnancy Outcomes. | Lost to follow up | 1 Subjects |