CClinicalTrials.gg
CompletedNCT03438006Updated Sep 8, 2021Results posted

A Post Marketing Surveillance (PMS) Study to Monitor the Safety of GlaxoSmithKline (GSK) Biologicals' Human Papillomavirus (HPV) Vaccine in Female Chinese Subjects

An observational study in Cervical Intraepithelial Neoplasia, sponsored by GlaxoSmithKline. Completed at 7 sites in China. Open to female participants aged 9 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-09-08.

Sponsored by GlaxoSmithKline · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
3,016
Ages
9 Years to 45 Years
Sex
Female
01

Study 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.

02

Conditions studied

  • Cervical Intraepithelial Neoplasia

Keywords

  • Safety
  • Human Papillomavirus Vaccine
  • Adverse Event Following Immunization
03

Who can participate

Ages eligible
9 Years to 45 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

Healthy female Chinese subjects aged between 9 and 45 years, vaccinated on a voluntary basis as per standard practice.

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

Exclusion Criteria:

  • Child in care
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
3,016 participants (actual)
Patient registry
No

Groups and cohorts

  • Cervarix group

    Healthy female Chinese subjects aged between 9 and 45 years, vaccinated according to the Prescribing Information (PI) as per routine practice.

    Other: Safety data collection (following routine vaccination)

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.

05

What researchers measure

Primary outcomes

  1. 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)

Secondary outcomes

  1. 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))

  2. 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))

  3. 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))

06

Results

Posted Sep 8, 2021

Participant flow

The study was conducted at 8 centres in China

Participant flow — Overall Study
MilestoneCervarix Group
Started3013
Completed2895
Not completed118
Withdrew: Adverse event1
Withdrew: Lost to follow-up67
Withdrew: Consent withdrawal not due to adv. event47
Withdrew: Not willing / not able to be contacted3

Outcome measures

PrimaryNumber 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)
Reported as:
Count of participants · Participants
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)
ParticipantsCervarix Group
Dose 149
Dose 255
Dose 356
Across doses147
Grade 31
Related2
SecondaryNumber 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))
Reported as:
Count of participants · Participants
Number of Participants With Any, Fatal and Vaccine Related Serious AEFIs (Across Doses)
ParticipantsCervarix Group
Any22
Fatal0
Related0
SecondaryNumber 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))
Reported as:
Count of participants · Participants
Number of Participants With Any, Grade 3 and Vaccine Related Potential Immune Mediated Diseases (pIMDs) (Across Doses)
ParticipantsCervarix Group
Any1
Grade 30
Related0
SecondaryNumber 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))
Reported as:
Count of participants · Participants
Number of Participants Reporting Pregnancies and Outcomes of Reported Pregnancies
ParticipantsCervarix Group
Live infant no apparent congenital anomaly34
Live infant congenital anomaly1
Elective termination no apparent congenital anomaly20
Elective termination congenital anomaly0
Spontaneous abortion no apparent congenital anomaly1
Spontaneous abortion congenital anomaly0
Stillbirth no apparent congenital anomaly0
Stillbirth congenital anomaly0
Ectopic pregnancy4
Molar pregnancy0
Pregnancies lost to follow-up5
Pregnancy ongoing0

Adverse events

Collected over Medically attended Adverse Events Following Immunisation (AEFI): During 30-Days after each vaccination (administered on Day 1, Month 1 and Month 6). Serious AEFI: During the entire study period [starting at the first immunisation (Day 1) and ending either 12 months following the third immunisation (Month 18) or 24 months following the first immunisation with Cervarix (Month 24), whichever occured first].. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cervarix Group0/3,013 (0%)22/3,013 (0.7%)143/3,013 (4.7%)
Most frequent serious events
Showing 10 of 32
Most frequent serious events
EventCervarix Group
PneumoniaInfections and infestations4/3013
Ectopic pregnancyPregnancy, puerperium and perinatal conditions4/3013
BronchitisInfections and infestations2/3013
Abortion inducedSurgical and medical procedures2/3013
AnaemiaBlood and lymphatic system disorders1/3013
ThrombocytopeniaBlood and lymphatic system disorders1/3013
Glycogen storage disease type ICongenital, familial and genetic disorders1/3013
Type V hyperlipidaemiaCongenital, familial and genetic disorders1/3013
GastritisGastrointestinal disorders1/3013
Hepatic function abnormalHepatobiliary disorders1/3013
Most frequent other events
Showing 10 of 71
Most frequent other events
EventCervarix Group
Upper respiratory tract infectionInfections and infestations30/3013
BronchitisInfections and infestations24/3013
TonsillitisInfections and infestations12/3013
PyrexiaGeneral disorders10/3013
PharyngitisInfections and infestations9/3013
GastroenteritisInfections and infestations5/3013
Urinary tract infectionInfections and infestations5/3013
GastritisGastrointestinal disorders4/3013
Influenza like illnessGeneral disorders4/3013
NasopharyngitisInfections and infestations4/3013

Baseline characteristics

Age, Continuous
Age, Continuous(YEARS)Cervarix Group
Mean30.6 ± 9.2
Sex: Female, Male
Sex: Female, Male(Participants)Cervarix Group
Female3013
Male0
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Cervarix Group
Asian - East Asian Heritage3013
07

Study locations

7 sites
  • GSK Investigational Site
    Foshan, Guangdong 528000, China
  • GSK Investigational Site
    Shenzhen, Guangdong 518000, China
  • GSK Investigational Site
    Shenzhen, Guangdong 518020, China
  • GSK Investigational Site
    Changzhou, Jiangsu 213100, China
  • GSK Investigational Site
    Chengdu, Sichuan 610000, China
  • GSK Investigational Site
    Shanghai, 200030, China
  • GSK Investigational Site
    Shanghai, 200136, China
08

References and documents

Study documents

  • Study protocol · Jun 27, 2018
  • Statistical analysis plan · Nov 4, 2020

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03438006
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Feb 19, 2018
Start date
May 31, 2018
Primary completion
Dec 3, 2020
Completion
Dec 3, 2020
Results posted
Sep 8, 2021
Last update
Sep 8, 2021

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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