Evaluation of Long-term Immunogenicity and Safety of a Human Papillomavirus (HPV) Vaccine in Healthy Female Subjects.

Follow-up Study to Evaluate the Long-term Immunogenicity and Safety of a HPV Vaccine (GSK 580299) in Healthy Female Subjects

Infection with human papillomavirus (HPV) has been clearly established as the necessary cause of cervical cancer. This study is designed to evaluate the long-term immunogenicity and safety of the 580299 HPV vaccine up to 10 years after administration of the first dose of HPV vaccine (Month 0) administered in the primary study 580299/013. This protocol posting deals with objectives & outcome measures of the extension phase from Month 60 to Month 120. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT00196924). The objectives & outcome measures of the extension phase up to Month 48 are presented in a separate protocol posting (NCT00316706).

Study Overview

• Status: Completed
• Conditions: Infections, Papillomavirus; Papillomavirus Vaccines
• Intervention / Treatment: Procedure: Blood sampling

Detailed Description

Subjects were aged 10-14 years at the time of entry into the primary study. No vaccine will be administered in this extension study.

Results on outcome measures describing analyses on other studies are not reported in this record. Please refer to the records mentioned in the respective outcome measure titles.

• Study Type: Interventional
• Enrollment (Actual): 632
• Phase: Phase 3

Contacts and Locations

Study Locations

• Colombia
  • Bogota, Colombia
    • 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, 68161
      • 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
    • Flensburg, Schleswig-Holstein, Germany, 24937
      • GSK Investigational Site
    • Harrislee, Schleswig-Holstein, Germany, 24955
      • GSK Investigational Site
    • Niebuell, Schleswig-Holstein, Germany, 25899
      • GSK Investigational Site
  • Thueringen
    • Weimar, Thueringen, Germany, 99423
      • GSK Investigational Site
• Honduras
  • Francisco Morazan
    • Tegucigalpa, Francisco Morazan, Honduras, 11101
      • GSK Investigational Site
• Panama
  • La Chorrera, Panama
    • GSK Investigational Site
  • Panamá
    • Arraijan/Vista Alegre, Panamá, Panama
      • GSK Investigational Site
• Taiwan
  • Taipei, Taiwan, 10002
    • GSK Investigational Site
  • Taoyuan, Taiwan, 333
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 24 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Subjects who the investigator believes that they and/or their parents or legally acceptable representative (LAR) can and will comply with the requirements of the protocol should be enrolled in the study.
• A female enrolled in the immunogenicity subset of study 580299-013, who received three doses of HPV vaccine and participated in the extension study of 580299-013.
• Written informed assent obtained from the subject. For subjects below the legal age of consent, written informed consent must be 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.
• Use of any investigational or non-registered product (drug or vaccine) or planned use during the study period.
• Administration or planned administration of any HPV vaccine, other than the vaccine administered in study 580299-013.
• Chronic administration of immunosuppressants or other immune-modifying drugs occurring within the three months preceding study entry.
• Administration of immunoglobulins and/or any blood products occurring within the three months preceding study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cervarix Group; Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule.	Procedure: Blood sampling; Blood samples were to be collected at Months 60, 72, 84, 96, 108 and 120

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values.	Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer < 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer >= 8 or 7 EL.U/mL prior to vaccination.	At Month 60
Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values.	Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer < 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer >= 8 or 7 EL.U/mL prior to vaccination.	At Month 72
Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values.	Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer < 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer >= 8 or 7 EL.U/mL prior to vaccination.	At Month 84
Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values.	Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer < 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer >= 8 or 7 EL.U/mL prior to vaccination.	At Month 96
Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers	Anti-HPV-16 and 18 antibody titers are given in Geometric Mean Titers (GMTs) in Enzyme-linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).	At Month 60
Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers	Anti-HPV-16 and 18 antibody titers are given in Geometric Mean Titers (GMTs) in Enzyme-linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).	At month 72
Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers	Anti-HPV-16 and 18 antibody titers are given in Geometric Mean Titers (GMTs) in Enzyme-linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).	At Month 84
Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers	Anti-HPV-16 and 18 antibody titers are given in Geometric Mean Titers (GMTs) in Enzyme-linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).	At Month 96
Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values.	Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer < 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer >= 8 or 7 EL.U/mL prior to vaccination.	At Month 108
Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers	Anti-HPV-16 and 18 antibody titers are given in Geometric Mean Titers (GMTs) in Enzyme-linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).	At Month 108
Anti-human Papillomavirus-16 and 18 (Anti-HPV-16/18) Antibody Titers	Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer < 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer >= 8 or 7 EL.U/mL prior to vaccination.	At Month 120
Number of Seroconverted Subjects With Anti-HPV-16/18 Antibody Titers Equal to or Above Cut-off Values.	Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer < 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer >= 8 or 7 EL.U/mL prior to vaccination.	At Month 120

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With 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.	From Month 48 to Month 60
Number of Subjects With 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.	From Month 60 to Month 72
Number of Subjects With 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.	From Month 72 to Month 84
Number of Subjects With 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.	From Month 84 to Month 96
Number of Subjects With 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.	From Month 96 to Month 108
Number of Subjects With 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.	From Month 108 to Month 120

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Schwarz TF, Huang LM, Lin TY, Wittermann C, Panzer F, Valencia A, Suryakiran PV, Lin L, Descamps D. Long-term immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in 10- to 14-year-old girls: open 6-year follow-up of an initial observer-blinded, randomized trial. Pediatr Infect Dis J. 2014 Dec;33(12):1255-61. doi: 10.1097/INF.0000000000000460.
• Schwarz TF, Huang LM, Valencia A, Panzer F, Chiu CH, Decreux A, Poncelet S, Karkada N, Folschweiller N, Lin L, Dubin G, Struyf F. A ten-year study of immunogenicity and safety of the AS04-HPV-16/18 vaccine in adolescent girls aged 10-14 years. Hum Vaccin Immunother. 2019;15(7-8):1970-1979. doi: 10.1080/21645515.2019.1625644. Epub 2019 Jul 17.

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 (Actual): May 7, 2009
• Primary Completion (Actual): January 6, 2015
• Study Completion (Actual): January 6, 2015

Study Registration Dates

• First Submitted: March 26, 2009
• First Submitted That Met QC Criteria: April 7, 2009
• First Posted (Estimate): April 8, 2009

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: December 31, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: cervical cancer; HPV vaccine
• Other Study ID Numbers: 111375; 2008-000369-44 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Informed Consent Form
   Information identifier: 111375
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 111375
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 111375
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 111375
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 111375
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 111375
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: 111375
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register