Human Papilloma Virus (HPV) Vaccine Trial in Young Adolescent Women With GlaxoSmithKline Biologicals' (GSK Bio) HPV-16/18 Vaccine

A Long-term, Open Follow-up of the Immunogenicity and Safety of GSK Biologicals' HPV Vaccine (580299) in Healthy Female Subjects Vaccinated in Study HPV-013

This protocol posting deals with objectives & outcome measures of the extension phase up to Month 48. The objective of the extension study is to evaluate the long-term immunogenicity of the HPV 16/18 L1 VLP AS04 vaccine (for all subjects in the HPV Vaccine Group) by enzyme-linked immunosorbent assay (ELISA). The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT00196924).

The long-term follow-up study will be blinded until the primary study is unblinded and will be open for all visits subsequent to unblinding of primary study HPV-013 (NCT00196924). During the open phase, only subjects who received the HPV-16/18 VLP/AS04 vaccine during the primary study will continue their participation in the follow-up study until Month 48. Subjects in the Control group (Havrix®) will attend one further visit as their last study visit.

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

Study Overview

• Status: Completed
• Conditions: Cervical Intraepithelial Neoplasia; Papillomavirus Infection
• Intervention / Treatment: Biological: GSK Biologicals' HPV-16/18 Vaccine (Cervarix™); Biological: Havrix™

• Study Type: Interventional
• Enrollment (Actual): 1245
• Phase: Phase 3

Contacts and Locations

Study Locations

• Colombia
  • Bogota, Colombia
    • GSK Investigational Site
  • Bogota, Colombia, 805
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10315
    • GSK Investigational Site
  • Berlin, Germany, 10967
    • GSK Investigational Site
  • Hamburg, Germany, 22307
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Deggingen, Baden-Wuerttemberg, Germany, 73326
      • GSK Investigational Site
    • Ettenheim, Baden-Wuerttemberg, Germany, 77955
      • GSK Investigational Site
    • Kehl, Baden-Wuerttemberg, Germany, 77694
      • GSK Investigational Site
    • Mannheim, Baden-Wuerttemberg, Germany, 68167
      • GSK Investigational Site
    • Tauberbischofsheim, Baden-Wuerttemberg, Germany, 97941
      • GSK Investigational Site
  • Bayern
    • Weilheim, Bayern, Germany, 82362
      • GSK Investigational Site
    • Wuerzburg, Bayern, Germany, 97070
      • GSK Investigational Site
  • Mecklenburg-Vorpommern
    • Buetzow, Mecklenburg-Vorpommern, Germany, 18246
      • GSK Investigational Site
    • Rostock, Mecklenburg-Vorpommern, Germany, 18109
      • GSK Investigational Site
  • Niedersachsen
    • Wolfenbuettel, Niedersachsen, Germany, 38302
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Bochum, Nordrhein-Westfalen, Germany, 44866
      • GSK Investigational Site
    • Willich, Nordrhein-Westfalen, Germany, 47877
      • GSK Investigational Site
  • Rheinland-Pfalz
    • Trier, Rheinland-Pfalz, Germany, 54290
      • GSK Investigational Site
  • Schleswig-Holstein
    • Brunsbuettel, Schleswig-Holstein, Germany, 25541
      • GSK Investigational Site
    • Flensburg, Schleswig-Holstein, Germany, 24937
      • GSK Investigational Site
    • Harrislee, Schleswig-Holstein, Germany, 24955
      • GSK Investigational Site
    • Husum, Schleswig-Holstein, Germany, 25813
      • GSK Investigational Site
    • Niebuell, Schleswig-Holstein, Germany, 25899
      • GSK Investigational Site
  • Thueringen
    • Weimar, Thueringen, Germany, 99425
      • GSK Investigational Site
• Honduras
  • Comayaguela, Honduras
    • GSK Investigational Site
• Panama
  • Panamá
    • La Chorrera, Panamá, Panama
      • GSK Investigational Site
• Taiwan
  • Taipei, Taiwan, 100
    • GSK Investigational Site
  • Tao Yuan County, Taiwan, 333
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• A female who enrolled in the immunological subset of the 580299-013 study, received the three doses of vaccine/control according to the treatment allocation and completed the 580299-013 study.
• Written informed assent obtained from the subject and written informed consent obtained from a parent or legally acceptable representative of the subject.

Exclusion Criteria:

• 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 (pharmaceutical product or device).
• Use of any investigational or non-registered product (drug or vaccine) or planned use during the study period.
• Chronic administration of immunosuppressants or other immune-modifying drugs occurring less than 3 months prior to blood sampling.
• Administration of immunoglobulins and/or any blood products within the 3 months preceding blood sampling.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cervarix Group; Subjects received 3 doses of GSK Biologicals' HPV-16/18 Vaccine (Cervarix™) during the primary study (NCT00196924). Subjects from this group continued the long-term follow-up study until Month 48.	Biological: GSK Biologicals' HPV-16/18 Vaccine (Cervarix™); Three doses of vaccine administrerd intramuscularly according to 0, 1, 6 month schedule
Active Comparator: Havrix Group; Subjects received 3 doses of Havrix™ (hepatitis A vaccine [HAV]) during the primary study (NCT00196924). Subjects from the this group completed the study at Month 24.	Biological: Havrix™; Three doses of vaccine administrerd intramuscularly according to 0, 1, 6 month schedule.

What is the study measuring?

Primary 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 18, 24, 36 and 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Titers of Anti-3-O-desacyl-4'-Monophosphoryl Lipid A (Anti-MPL) Antibodies During the Initial 2 Years Follow-up	Titers are given as Geometric Mean Titers (GMTs) expressed as EL.U/mL.	At Months 18 and 24
Titers of Anti-3-O-desacyl 4'-Monophosphoryl Lipid A (Anti-MPL) Antibodies During the Last 2 Years Follow-up	Titers are given as Geometric Mean Titers (GMTs) expressed as EL.U/mL.	At Month 36 and 48
Number of Subjects Reporting Pregnancies, Serious Adverse Events (SAEs), New Onset Chronic Diseases (NOCDs), and Conditions Prompting Emergency Room (ER) Visits or Physician Visits That Are Not Related to Common Diseases During the First 2 Years Follow-up	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. New onset of chronic diseases (NOCDs) assessed include e.g. autoimmune disorders, asthma, type I diabetes.	From Month 18 to Month 24
Number of Subjects Reporting Pregnancies, Serious Adverse Events (SAEs), New Onset Chronic Diseases (NOCDs), and Conditions Prompting Emergency Room During the Last 2 Years Follow-up	Serious adverse events assessed include medical occurrences that result 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. New onset of chronic diseases (NOCDs) assessed include e.g. autoimmune disorders, asthma, type I diabetes.	From Month 24 to Month 48

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Schwarz TF, Huang LM, Medina DM, Valencia A, Lin TY, Behre U, Catteau G, Thomas F, Descamps D. Four-year follow-up of the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine when administered to adolescent girls aged 10-14 years. J Adolesc Health. 2012 Feb;50(2):187-94. doi: 10.1016/j.jadohealth.2011.11.004.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): January 1, 2009

Study Registration Dates

• First Submitted: April 19, 2006
• First Submitted That Met QC Criteria: April 19, 2006
• First Posted (Estimate): April 21, 2006

Study Record Updates

• Last Update Posted (Estimate): September 18, 2012
• Last Update Submitted That Met QC Criteria: September 13, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Prophylaxis HPV-16/18 infections and cervical neoplasia
• Additional Relevant MeSH Terms: Virus Diseases; Infections; Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; DNA Virus Infections; Tumor Virus Infections; Carcinoma in Situ; Neoplasms; Cervical Intraepithelial Neoplasia; Papillomavirus Infections
• Other Study ID Numbers: 104896 (month 18 FU); 104902 (GSK); 104904 (Other Identifier: GSK); 104918 (Other Identifier: GSK)