Study to Evaluate the Immune Response and Safety of GSK Biologicals' HPV Vaccine in Healthy Women Aged 18-35 Years

Phase 3, Open, Age-stratified Study to Assess Immunogenicity and Safety of GSK Biologicals' HPV-16/18 Vaccine Administered Intramuscularly According to 3-dose Schedule (0,1,6 Months) in Healthy Female Subjects Aged 15 - 55 Years and Long Term Follow-up

Human papillomavirus infection has clearly been recognized as the cause of cervical cancer. The infection of the cervix by certain oncogenic types of HPV, if not cleared, can lead to cervical cancer in women. This study will evaluate the immunogenicity and safety of the HPV-16/18 L1 VLP AS04 vaccine.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study Overview

• Status: Completed
• Conditions: Infections, Papillomavirus
• Intervention / Treatment: Biological: Placebo; Biological: HPV-16/18 L1 VLP AS04 (Cervarix TM)

Detailed Description

The protocol was primarily amended for the following reasons:

• Merck's tetravalent HPV vaccine, Gardasil®, has been licensed and is now becoming commercially available in an increasing number of countries. Therefore, the study procedures were revised to include questions at every visit to determine if subjects have received an HPV vaccine outside of the study.
• It was decided to offer GSK Biologicals' HPV vaccine to all subjects in the control group at the end of the study. The HPV vaccine will be offered to these subjects based on its local indication once the vaccine is marketed in Malaysia.

• Study Type: Interventional
• Enrollment (Actual): 271
• Phase: Phase 3

Contacts and Locations

Study Locations

• Malaysia
  • Kerajaan Persekutuan Putrajaya, Malaysia, 62250
    • GSK Investigational Site
  • Kuala Lumpur, Malaysia, 50603
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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 female from Malaysia between, and including, 18 and 35 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Subjects must have a negative urine pregnancy test.
• Subjects of childbearing potential at the time of study entry must be abstinent or must be using an effective method of birth control for 30 days prior to vaccination and must agree to continue such precautions for two months after completion of the vaccination series.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Chronic administration (defined as more than 14 days) 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 the first dose of vaccine. Administration of routine vaccines up to 8 days before the first 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
• Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).
• Hypersensitivity to latex.
• Acute disease at the time of enrolment.
• Known acute or chronic, clinically significant neurologic, pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests.
• History of chronic condition(s) requiring treatment.
• Administration of immunoglobulins and/or any blood product within three months preceding the first dose of study vaccine(s) or planned administration during the study period. Enrolment will be deferred until the subject is outside of specified window.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cervarix Group; Subjects received 3 doses of HPV-16/18 L1 VLP AS04 (Cervarix™) according to a 0, 1, 6-month schedule.	Biological: HPV-16/18 L1 VLP AS04 (Cervarix TM); Three doses of vaccine administered intramuscularly according to a 0, 1, 6-month schedule.; Other Names: GSK Biologicals' HPV-16/18 VLP/AS04 vaccine
Placebo Comparator: Placebo Group; Subjects received 3 doses of Placebo according to a 0, 1, 6-month schedule.	Biological: Placebo; Three doses of vaccine administered intramuscularly according to a 0, 1, 6-month schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Who Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies	Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subjects seronegative before vaccination. Cut-off values assessed include 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies	Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).	At Month 0 and Month 7
Number of Subjects Reporting Solicited Symptoms	Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include arthralgia, fatigue, fever, gastro-intestinal symptoms, headache, myalgia, rash and urticaria.	During the 7 days after each vaccination
Number of Subjects Reporting Unsolicited Adverse Events (AEs)	Unsolicited adverse event = Any adverse event (AE) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.	Within 30 days after any vaccination
Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (AEs)	NOCDs assessed include e.g. autoimmune disorders, asthma, type I diabetes, allergies,... Medically significant AEs assessed include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or SAEs that are not related to common diseases.	Throughout the study period (up to Month 7)
Number of Subjects Reporting Serious Adverse Events	Serious adverse events assessed include medical occurrences that results in death, is 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.	Throughout the study period (up to Month 7)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Verstraeten T, Descamps D, David MP, Zahaf T, Hardt K, Izurieta P, Dubin G, Breuer T. Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines. Vaccine. 2008 Dec 2;26(51):6630-8. doi: 10.1016/j.vaccine.2008.09.049.

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: September 25, 2006
• Primary Completion (Actual): December 21, 2007
• Study Completion (Actual): December 21, 2007

Study Registration Dates

• First Submitted: June 28, 2006
• First Submitted That Met QC Criteria: June 28, 2006
• First Posted (Estimate): June 29, 2006

Study Record Updates

• Last Update Posted (Actual): July 20, 2018
• Last Update Submitted That Met QC Criteria: May 24, 2018
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Double-blind; Cervical cancer; Human Papillomavirus (HPV); Cervical neoplasia; HPV-16/18 L1 VLP AS04; AS04
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 105926

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. Clinical Study Report
   Information identifier: 105926
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 105926
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 105926
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 105926
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 105926
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: 105926
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register