Cervical Intraepithelial Neoplasia
Conditions
Keywords
Safety, Human Papillomavirus Vaccine, Adverse Event Following Immunization
Brief summary
The purpose of this prospective, multi-centre, PMS cohort study was to monitor the safety of Cervarix, which is the first HPV vaccine licensed for use in China, to help prevent cervical cancer caused by HPV types 16 and 18. The vaccine was approved by National Drug Administration of China (CNDA), in July 2016. As per the CNDA commitment, this study collected data regarding the safety of the vaccine, related information on potential immune-mediated diseases (pIMDs); which are diseases that could affect the immune system, and the effect on pregnancy outcomes (POs) including birth defects in the newborn. Cervarix was approved for use in females between 9-25 years of age, for the prevention of cervical cancer, cervical intraepithelial neoplasia grade 1 (CIN1), cervical intraepithelial neoplasia grade 2, grade 3 (CIN 2/3) and adenocarcinoma in situ caused by high-risk human papillomavirus (HR-HPV) types 16 and 18. In May 2018, Cervarix was also approved for use in women of age up to 45 years. The exposed set (ES) comprised 3013 subjects, who were vaccinated with Cervarix, on a voluntary basis, as per standard practice. The study collected information on any adverse event following immunisation, pIMDs, POs and congenital anomalies.
Interventions
OTHERSafety data collection (following routine vaccination)
This study assessed the safety of GSK Biologicals' Human papillomavirus (HPV) vaccine when administered routinely according to the Prescribing Information in female Chinese subjects aged between 9 and 45 years. The intervention consisted in the active surveillance of adverse events following immunization and pregnancy outcomes if the vaccine was administered inadvertently during pregnancy. Information of potential adverse events and pregnancy outcomes were collected at immunisation visits, telephone contacts and through spontaneous reporting by the patient/LAR/physician.
Sponsors
GlaxoSmithKline
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
9 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Any Chinese female subject aged between 9 and 45 years, at the time of first vaccination dose, who received voluntary vaccination. * Subjects for whom the investigator believed that they or their parent(s)/LAR(s) could and complied with the requirements mentioned in the protocol (e.g., return for the subsequent dose of vaccination and follow-up visits) were included in the study. * Written informed consent was obtained from the subject. For subjects who were below the legal age of consent, written informed consent were obtained from the parent(s)/LAR(s) of the subject and informed assent were obtained from the subject according to EC requirement as well as local law.
Exclusion criteria
• Child in care
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any (Following Each Dose and Across Doses), Grade 3 (Across Doses) and Vaccine Related (Across Doses) Medically Attended Adverse Events Following Immunisation (AEFIs) | During the 30-day period following each immunisation with Cervarix (administered on Day 1, Month 1 and Month 6) | An adverse event following immunisation (AEFI) is defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a vaccine. Medically attended AEFIs are defined as events leading to an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits. Any Medically attended AEFIS are presented for each dose and across doses. Grade 3 Medically attended AEFI = an AEFI which prevented normal, everyday activities. Related Medically Attended AEFI = AEFI assessed by the investigator as related to the vaccination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any, Fatal and Vaccine Related Serious AEFIs (Across Doses) | Throughout the study period (From Day 1 to either 12 months following the third immunisation (Month 18) or 24 months following the first immunisation with Cervarix (Month 24) whichever occured first)) | Serious AEFIs assessed included medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a participant. Any serious AEFI = If a medically attended AEFI led to hospitalisation (or met any other serious AEFI criteria). Fatal Serious AEFIs are those events that resulted in death. Related Serious AEFIs= AEFIs assessed by the investigator as causally related to the study vaccination. |
| Number of Participants With Any, Grade 3 and Vaccine Related Potential Immune Mediated Diseases (pIMDs) (Across Doses) | Throughout the study period (from Day 1 up to either 12 months following the third immunisation (Month 18) or 24 months following the first immunisation with Cervarix (Month 24), whichever occured first)) | pIMDs are a subset of AEFIs that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which might or might not have an autoimmune aetiology. Any was defined as the occurrence of any pIMD regardless of intensity grade or relation to vaccination. Grade 3 pIMDs = pIMDs which prevented normal, everyday activities. Related pIMDs = pIMDs assessed by the investigator as related to the vaccination. |
| Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies | Throughout the study period (from Day 1 up to either 12 months following the third immunisation (Month 18) or 24 months following the first immunisation with Cervarix (Month 24), whichever occured first)) | The number of participants reporting pregnancies and outcomes of reported pregnancies (elective abortion for medical reasons, spontaneous abortion or congenital anomaly) when Cervarix was administered to the participant, inadvertently within 60 days before pregnancy onset, or any time during pregnancy, was reported. |
Countries
China
Participant flow
Recruitment details
The study was conducted at 8 centres in China
Pre-assignment details
Out of 3016 participants enrolled in the study, 3 participants did not receive any vaccination and therefore were not included in any analysis.
Participants by arm
| Arm | Count |
|---|---|
| Cervarix Group Healthy female Chinese participants aged between 9 and 45 years, vaccinated according to the Prescribing Information (PI) as per routine practice. | 3,013 |
| Total | 3,013 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | CONSENT WITHDRAWAL NOT DUE TO ADV. EVENT | 47 |
| Overall Study | Lost to Follow-up | 67 |
| Overall Study | NOT WILLING / NOT ABLE TO BE CONTACTED | 3 |
Baseline characteristics
| Characteristic | Cervarix Group |
|---|---|
| Age, Continuous | 30.6 YEARS STANDARD_DEVIATION 9.2 |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 3013 Participants |
| Sex: Female, Male Female | 3013 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3,013 |
| other Total, other adverse events | 143 / 3,013 |
| serious Total, serious adverse events | 22 / 3,013 |
Outcome results
Primary
Number of Participants With Any (Following Each Dose and Across Doses), Grade 3 (Across Doses) and Vaccine Related (Across Doses) Medically Attended Adverse Events Following Immunisation (AEFIs)
An adverse event following immunisation (AEFI) is defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a vaccine. Medically attended AEFIs are defined as events leading to an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits. Any Medically attended AEFIS are presented for each dose and across doses. Grade 3 Medically attended AEFI = an AEFI which prevented normal, everyday activities. Related Medically Attended AEFI = AEFI assessed by the investigator as related to the vaccination.
Time frame: During the 30-day period following each immunisation with Cervarix (administered on Day 1, Month 1 and Month 6)
Population: Analysis was based on the Exposed Set (ES) which included all participants exposed to Cervarix and who provided safety data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Participants With Any (Following Each Dose and Across Doses), Grade 3 (Across Doses) and Vaccine Related (Across Doses) Medically Attended Adverse Events Following Immunisation (AEFIs) | Dose 1 | 49 Participants |
| Cervarix Group | Number of Participants With Any (Following Each Dose and Across Doses), Grade 3 (Across Doses) and Vaccine Related (Across Doses) Medically Attended Adverse Events Following Immunisation (AEFIs) | Dose 2 | 55 Participants |
| Cervarix Group | Number of Participants With Any (Following Each Dose and Across Doses), Grade 3 (Across Doses) and Vaccine Related (Across Doses) Medically Attended Adverse Events Following Immunisation (AEFIs) | Dose 3 | 56 Participants |
| Cervarix Group | Number of Participants With Any (Following Each Dose and Across Doses), Grade 3 (Across Doses) and Vaccine Related (Across Doses) Medically Attended Adverse Events Following Immunisation (AEFIs) | Across doses | 147 Participants |
| Cervarix Group | Number of Participants With Any (Following Each Dose and Across Doses), Grade 3 (Across Doses) and Vaccine Related (Across Doses) Medically Attended Adverse Events Following Immunisation (AEFIs) | Grade 3 | 1 Participants |
| Cervarix Group | Number of Participants With Any (Following Each Dose and Across Doses), Grade 3 (Across Doses) and Vaccine Related (Across Doses) Medically Attended Adverse Events Following Immunisation (AEFIs) | Related | 2 Participants |
Secondary
Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies
The number of participants reporting pregnancies and outcomes of reported pregnancies (elective abortion for medical reasons, spontaneous abortion or congenital anomaly) when Cervarix was administered to the participant, inadvertently within 60 days before pregnancy onset, or any time during pregnancy, was reported.
Time frame: Throughout the study period (from Day 1 up to either 12 months following the third immunisation (Month 18) or 24 months following the first immunisation with Cervarix (Month 24), whichever occured first))
Population: The analysis was based on the ES, which included all participants exposed to Cervarix and who reported pregnancies and/or outcomes of reported pregnancies.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies | Pregnancy ongoing | 0 Participants |
| Cervarix Group | Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies | Live infant no apparent congenital anomaly | 34 Participants |
| Cervarix Group | Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies | Live infant congenital anomaly | 1 Participants |
| Cervarix Group | Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies | Elective termination no apparent congenital anomaly | 20 Participants |
| Cervarix Group | Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies | Elective termination congenital anomaly | 0 Participants |
| Cervarix Group | Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies | Spontaneous abortion no apparent congenital anomaly | 1 Participants |
| Cervarix Group | Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies | Spontaneous abortion congenital anomaly | 0 Participants |
| Cervarix Group | Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies | Stillbirth no apparent congenital anomaly | 0 Participants |
| Cervarix Group | Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies | Stillbirth congenital anomaly | 0 Participants |
| Cervarix Group | Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies | Ectopic pregnancy | 4 Participants |
| Cervarix Group | Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies | Molar pregnancy | 0 Participants |
| Cervarix Group | Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies | Pregnancies lost to follow-up | 5 Participants |
Secondary
Number of Participants With Any, Fatal and Vaccine Related Serious AEFIs (Across Doses)
Serious AEFIs assessed included medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a participant. Any serious AEFI = If a medically attended AEFI led to hospitalisation (or met any other serious AEFI criteria). Fatal Serious AEFIs are those events that resulted in death. Related Serious AEFIs= AEFIs assessed by the investigator as causally related to the study vaccination.
Time frame: Throughout the study period (From Day 1 to either 12 months following the third immunisation (Month 18) or 24 months following the first immunisation with Cervarix (Month 24) whichever occured first))
Population: Analysis was based on the Exposed Set (ES) which included all participants exposed to Cervarix.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Participants With Any, Fatal and Vaccine Related Serious AEFIs (Across Doses) | Any | 22 Participants |
| Cervarix Group | Number of Participants With Any, Fatal and Vaccine Related Serious AEFIs (Across Doses) | Fatal | 0 Participants |
| Cervarix Group | Number of Participants With Any, Fatal and Vaccine Related Serious AEFIs (Across Doses) | Related | 0 Participants |
Secondary
Number of Participants With Any, Grade 3 and Vaccine Related Potential Immune Mediated Diseases (pIMDs) (Across Doses)
pIMDs are a subset of AEFIs that included autoimmune diseases and other inflammatory and/or neurologic disorders of interest which might or might not have an autoimmune aetiology. Any was defined as the occurrence of any pIMD regardless of intensity grade or relation to vaccination. Grade 3 pIMDs = pIMDs which prevented normal, everyday activities. Related pIMDs = pIMDs assessed by the investigator as related to the vaccination.
Time frame: Throughout the study period (from Day 1 up to either 12 months following the third immunisation (Month 18) or 24 months following the first immunisation with Cervarix (Month 24), whichever occured first))
Population: Analysis was based on the Exposed Set (ES) which included all participants exposed to Cervarix.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cervarix Group | Number of Participants With Any, Grade 3 and Vaccine Related Potential Immune Mediated Diseases (pIMDs) (Across Doses) | Any | 1 Participants |
| Cervarix Group | Number of Participants With Any, Grade 3 and Vaccine Related Potential Immune Mediated Diseases (pIMDs) (Across Doses) | Grade 3 | 0 Participants |
| Cervarix Group | Number of Participants With Any, Grade 3 and Vaccine Related Potential Immune Mediated Diseases (pIMDs) (Across Doses) | Related | 0 Participants |