Immunogenicity and Safety Study of GSK Biologicals' Human Papillomavirus 580299 Vaccine in Healthy Female Subjects

Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Human Papillomavirus (HPV) 580299 Vaccine in Healthy Chinese Female Subjects

This study is designed to evaluate the immunogenicity and safety of GlaxoSmithKline Biologicals' human papillomavirus (HPV) vaccine in pre-teen and adolescent female subjects aged 9 - 17 years. One group of subjects will receive the HPV vaccine and the other group will receive the control.

Study Overview

• Status: Completed
• Conditions: Infections, Papillomavirus
• Intervention / Treatment: Biological: CervarixTM; Other: Control

• Study Type: Interventional
• Enrollment (Actual): 750
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Taizhou, Jiangsu, China, 225300
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 17 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Subjects who the investigator believes that they or their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol.
• Healthy Chinese females between and including 9 and 17 years of age at the time of the first vaccination.
• Written informed consent obtained from the parent(s)/LAR(s) of the subject and informed assent obtained from the subject, if appropriate, prior to enrolment.
• Healthy subjects as established by medical history and history-directed clinical examination before entering into the study.
• Subjects must not be pregnant. Absence of pregnancy will be verified with a urine pregnancy test before each vaccination.
• Subjects must be either of non-childbearing potential, or if of childbearing potential, they must be abstinent or have practiced adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and agree to continue such precautions for 2 months after completion of the vaccination series.

Exclusion Criteria:

• Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
• Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after (i.e., Days 0-29) the first dose of vaccine.
• 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.
• A subject planning to become pregnant, likely to become pregnant or planning to discontinue contraceptive precautions during the study period and up to two months after the last vaccine dose.
• Pregnant or breastfeeding. Subjects must be at least three months post-pregnancy and not breastfeeding to enter the study.
• Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the protocol during the study period.
• Previous administration of components of the study vaccine.
• History of chronic condition(s) requiring treatment such as cancer or autoimmune disease.
• History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the vaccine.
• Hypersensitivity to latex.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• Acute disease at the time of enrolment.
• Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cervarix Group; Subjects received 3 doses of Cervarix vaccine. Cervarix vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Biological: CervarixTM; Subjects will receive three doses of the Cervarix vaccine intramuscularly according to a 0, 1, 6-month schedule.
Experimental: Placebo Group; Subjects received 3 doses of placebo. Placebo vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm according to a 0, 1, 6-month schedule.	Other: Control; Subjects will receive three doses of control intramuscularly according to a 0, 1, 6-month schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers (GMTs) for Antibodies Against Human Papillomavirus (HPV)-16/18 Antigens	Titers were given as geometric mean titers and were measured by Enzyme-linked Immunosorbent Assay (ELISA) and expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).	One month after the third dose (at Month 7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies	Seroconversion is defined as the appearance of anti-HPV-16 and/or anti- HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the sera of subjects seronegative before vaccination. Cut-off values were 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti- HPV-18 antibodies.	At Month 7
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms	Solicited local symptoms assessed were pain, redness and swelling. Any was defined as any solicited local symptom reported irrespective of intensity. Grade 3 pain was defined as pain that prevented normal activity. Grade 3 redness and swelling were defined as redness/swelling above 50 millimeter (mm).	During the 7 days (Days 0 - 6) following each vaccination
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms	Solicited general symptoms assessed were arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, urticaria and fever (= axillary temperature above 37.0 degrees Celsius (°C). Grade 3 fever = axillary temperature above 39.0°C. Grade 3 urticaria = urticaria distributed on at least 4 body areas. For other symptoms, any = occurrence of any general symptom regardless of intensity grade or relation to vaccination and grade 3 = a general symptom that prevented normal activity. Related was a general symptom assessed by the investigator as causally related to the study vaccination.	During the 7 days (Days 0 - 6) following each vaccination
Number of Subjects Reporting Medically Significant Conditions (MSCs)	Medically significant conditions (MSCs) are defined as: adverse events (AEs) prompting emergency room or physician visits that are not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are 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. MSCs were collected regardless of causal relationship to vaccination and intensity.	Throughout the study period (from Day 0 up to Month 12)
Number of Subjects Reporting Pregnancies and Pregnancy Outcomes		Throughout the study period (from Day 0 up to Month 12)
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AEs)	Unsolicited AE covers any AE reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination. Grade 3 was an event that prevented normal activities and related was defined as an unsolicited AE assessed by the investigator to be causally related to the study vaccination.	Within 30 days (Days 0 - 29) after any vaccination
Number of Subjects Reporting Any and Related Serious Adverse Events (SAEs)	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.	Throughout the study period (from Day 0 up to Month 12)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Zhu F, Li J, Hu Y, Zhang X, Yang X, Zhao H, Wang J, Yang J, Xia G, Dai Q, Tang H, Suryakiran P, Datta SK, Descamps D, Bi D, Struyf F. Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Chinese girls and women aged 9 to 45 years. Hum Vaccin Immunother. 2014;10(7):1795-806. doi: 10.4161/hv.28702.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: October 24, 2009
• Primary Completion (Actual): December 8, 2010
• Study Completion (Actual): December 8, 2010

Study Registration Dates

• First Submitted: October 15, 2009
• First Submitted That Met QC Criteria: October 15, 2009
• First Posted (Estimate): October 16, 2009

Study Record Updates

• Last Update Posted (Actual): August 17, 2018
• Last Update Submitted That Met QC Criteria: June 28, 2018
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: China; Safety; Immunogenicity; Human papillomavirus; HPV vaccine
• Other Study ID Numbers: 112022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 112022
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 112022
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 112022
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 112022
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 112022
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: 112022
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register