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

A Prospective, Multi-centre Post Marketing Surveillance (PMS) Cohort Study to Monitor the Safety of GlaxoSmithKline (GSK) Biologicals' Human Papillomavirus (HPV)-16/18 L1 VLP AS04 Vaccine in Female Chinese Subjects Aged Between 9 and 45 Years, When Administered According to the Prescribing Information (PI) as Per Routine Practice.

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.

Study Overview

• Status: Completed
• Conditions: Cervical Intraepithelial Neoplasia
• Intervention / Treatment: Other: Safety data collection (following routine vaccination)

• Study Type: Observational
• Enrollment (Actual): 3016

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	During the 30-day period following each immunisation with Cervarix (administered on Day 1, Month 1 and Month 6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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))
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.	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))
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.	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))

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2018
• Primary Completion (Actual): December 3, 2020
• Study Completion (Actual): December 3, 2020

Study Registration Dates

• First Submitted: February 13, 2018
• First Submitted That Met QC Criteria: February 13, 2018
• First Posted (Actual): February 19, 2018

Study Record Updates

• Last Update Posted (Actual): September 8, 2021
• Last Update Submitted That Met QC Criteria: August 11, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Safety; Human Papillomavirus Vaccine; Adverse Event Following Immunization
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma in Situ; Cervical Intraepithelial Neoplasia
• Other Study ID Numbers: 207350

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No