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

• ClinicalTrials.gov Identifier: NCT00947115
• Recruitment Status: Completed
• First Posted: July 27, 2009
• Results First Posted: May 2, 2011
• Last Update Posted: October 30, 2020
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

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 GSK Biologicals' 580299 HPV vaccine up to 10 years after administration of the first dose of HPV vaccine (Month 0) in primary study NCT00196937. This protocol posting deals with objectives & outcome measures of the extension phase from Year 5 to Year 10. The objectives & outcome measures of the primary phase and extension phase up to year 4 are presented in a separate protocol posting (NCT00196937).

Condition or disease	Intervention/treatment	Phase
Infections, Papillomavirus	Procedure: Blood sampling; Procedure: Cervico-vaginal secretion (CVS) samples	Phase 3

Detailed Description:

Subjects were aged 15-55 years at the time of entry into the primary study (NCT00196937). No vaccine was 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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 525 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Follow-up Study to Evaluate the Long-term Immunogenicity and Safety of GlaxoSmithKline Biologicals' HPV (580299) Vaccine in Healthy Female Subjects
• Actual Study Start Date: September 22, 2009
• Actual Primary Completion Date: February 3, 2015
• Actual Study Completion Date: February 3, 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cervarix 15-25 years group; Women, aged 15 to 25 at the time of primary vaccination, who were vaccinated with Cervarix intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6-month schedule in the primary study HPV-014 (NCT00196937).	Procedure: Blood sampling; Blood samples were collected at Years 5, 6, 7, 8, 9 and 10.; Procedure: Cervico-vaginal secretion (CVS) samples; CVS samples were collected at Years 5, 6, 7, 8, 9 and 10 in subjects who volunteered for this procedure.
Experimental: Cervarix 26-45 years group; Women, aged 26 to 45 at the time of primary vaccination, who were vaccinated with Cervarix intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6-month schedule in the primary study HPV-014 (NCT00196937).	Procedure: Blood sampling; Blood samples were collected at Years 5, 6, 7, 8, 9 and 10.; Procedure: Cervico-vaginal secretion (CVS) samples; CVS samples were collected at Years 5, 6, 7, 8, 9 and 10 in subjects who volunteered for this procedure.
Experimental: Cervarix 46-55 years group; Women, aged 46 to 55 at the time of primary vaccination, who were vaccinated with Cervarix intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6-month schedule in the primary study HPV-014 (NCT00196937).	Procedure: Blood sampling; Blood samples were collected at Years 5, 6, 7, 8, 9 and 10.; Procedure: Cervico-vaginal secretion (CVS) samples; CVS samples were collected at Years 5, 6, 7, 8, 9 and 10 in subjects who volunteered for this procedure.

Outcome Measures

Primary Outcome Measures :

1. Anti-Human Papillomavirus (Anti-HPV)-16/18 Antibody Titers in Serum at Years 5, 6 and 7 [ Time Frame: At Years 5, 6 and 7 ]

   Anti-HPV-16/18 antibody titers are presented as Geometric Mean Titers (GMTs) and expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

   The immune response of the HPV-16/18 vaccine (as determined by anti-HPV-16/18 antibodies assessed by ELISA) in the HPV-060 study population was compared with the immune response obtained in study HPV-001 and its long-term follow-up studies HPV-007/HPV-023 at equivalent timepoints and with the immune response obtained after natural infection in subjects from study HPV-008.

   The immune response data for the efficacy studies HPV-001/HPV-007/HPV-023 can be found under the NCT record NCT00518336. The immune response data for the HPV-008 study can be found under the NCT record NCT00122681.

2. Anti-HPV-16/18 Antibody Titers in Serum at Years 8, 9 and 10 [ Time Frame: At Years 8, 9 and 10 ]

   Anti-HPV-16/18 antibody titers are presented as Geometric Mean Titers (GMTs) and expressed in EL.U/mL.

   The immune response of the HPV-16/18 vaccine (as determined by anti-HPV-16/18 antibodies assessed by ELISA) in the HPV-060 study population was compared with the immune response obtained in study HPV-001 and its long-term follow-up studies HPV-007/HPV-023 at equivalent timepoints and with the immune response obtained after natural infection in subjects from study HPV-008.

   The immune response data for the efficacy studies HPV-001/HPV-007/HPV-023 can be found under the NCT number NCT00518336. The immune response data for the HPV-008 study can be found under the NCT number NCT00122681.

3. Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies at Years 5, 6 and 7 [ Time Frame: At Years 5, 6 and 7 ]
   Seroconversion was defined as the appearance of anti-HPV-16 and anti- HPV-18 antibodies [i.e. antibody titer greater than or equal to (≥) the cut-off value] in the serum of subjects seronegative before vaccination in the primary study HPV-014 (NCT00196937). Cut-off values were 8 EL.U/mL for anti-HPV-16 antibody titers and 7 EL.U/mL for anti-HPV-18 antibody titers.
4. Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies at Years 8, 9 and 10 [ Time Frame: At Years 8, 9 and 10 ]
   Seroconversion was defined as the appearance of anti-HPV-16 and anti-HPV-18 antibodies (i.e. antibody titer ≥ the cut-off value) in the serum of subjects seronegative before vaccination in the primary study HPV-014 (NCT00196937). Cut-off values were 19 EL.U/mL for anti-HPV-16 antibody titers and 18 EL.U/mL for anti-HPV-18 antibody titers.

Secondary Outcome Measures :

1. Anti-HPV-16/18 Secretion Antibody Titers in Cervico-vaginal Secretion (CVS) Samples at Years 5 and 6 in a Subset of Subjects [ Time Frame: At Year 5 and Year 6 ]
   Anti-HPV-16/18 titers in CVS samples are presented as GMTs and expressed in EL.U/mL.
2. Anti-HPV-16/18 Secretion Antibody Titers in CVS Samples at Years 7, 8, 9 and 10 in a Subset of Subjects [ Time Frame: At Years 7, 8, 9 and 10 ]
   Anti-HPV-16/18 titers in CVS samples are presented as GMTs and expressed in EL.U/mL.
3. Total Immunoglobulin G (IgG) Secretion Antibody Titers in CVS Samples at Years 5 and 6 in a Subset of Subjects [ Time Frame: At Year 5 and Year 6 ]
   IgG antibody titers in CVS samples are presented as GMTs and expressed in microgram per milliliter (µg/mL).
4. Total IgG Secretion Antibody Titers in CVS Samples at Years 7, 8, 9, and 10 in a Subset of Subjects [ Time Frame: At Years 7, 8, 9 and 10 ]
   Total IgG antibody titers in CVS samples are presented as GMTs and expressed in microgram per milliliter (µg/mL).
5. Total IgG Antibody Titers in Serum at Years 5, 6 and 7 Based on the ATP Cohort for Immunogenicity [ Time Frame: At Years 5, 6 and 7 ]
   Total IgG antibody titers are presented as GMTs and expressed in µg/mL.
6. Total IgG Antibody Titers in Serum at Years 8, 9 and 10 Based on the ATP Cohort for Immunogenicity [ Time Frame: At Years 8, 9 and 10 ]
   Total IgG antibody titers are presented as GMTs and expressed in µg/mL.
7. Total IgG Antibody Titers in Serum at Years 5, 6 and 7 Based on the TVC [ Time Frame: At Years 5, 6 and 7 ]
   Total IgG antibody titers are presented as GMTs and expressed in µg/mL.
8. Total IgG Antibody Titers in Serum at Years 8, 9 and 10 Based on the TVC [ Time Frame: At Years 8, 9 and 10 ]
   Total IgG antibody titers are presented as GMTs and expressed in µg/mL.
9. Number of Subjects With Any Fatal or Vaccine-related SAEs (Including SAEs Related to Study Procedures and GlaxoSmithKline Biologicals' Concomitant Medication) From Year 4 in Primary Study HPV-014 (NCT00196937) to Year 5 in the Present Study [ Time Frame: From Year 4 in primary study HPV-014 (NCT00196937) up to Year 5 in present HPV-060 study ]
   SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject, or may have evolved into one of the outcomes listed above. Related SAE = SAE assessed by the investigator as causally related to the study vaccine administered in study HPV-014 (NCT00196937).
10. Number of Subjects With Any Fatal or Vaccine-related SAEs (Including SAEs Related to Study Procedures and GlaxoSmithKline Biologicals' Concomitant Medication) From Year 5 to Year 6 [ Time Frame: From Year 5 up to Year 6 ]
    SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject, or may have evolved into one of the outcomes listed above. Related SAE = SAE assessed by the investigator as causally related to the study vaccine administered in study HPV-014 (NCT00196937).
11. Number of Subjects With Any Fatal or Vaccine-related SAEs (Including SAEs Related to Study Procedures and GlaxoSmithKline Biologicals' Concomitant Medication) From Year 6 to Year 7 [ Time Frame: From Year 6 up to Year 7 ]
    SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject, or may have evolved into one of the outcomes listed above. Related SAE = SAE assessed by the investigator as causally related to the study vaccine administered in study HPV-014 (NCT00196937).
12. Number of Subjects With Any Fatal or Vaccine-related SAEs (Including SAEs Related to Study Procedures and GlaxoSmithKline Biologicals' Concomitant Medication) From Year 7 to Year 8 [ Time Frame: From Year 7 up to Year 8 ]
    SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject, or may have evolved into one of the outcomes listed above. Related SAE = SAE assessed by the investigator as causally related to the study vaccine administered in study HPV-014 (NCT00196937).
13. Number of Subjects With Any Fatal or Vaccine-related SAEs (Including SAEs Related to Study Procedures and GlaxoSmithKline Biologicals' Concomitant Medication) From Year 8 to Year 9 [ Time Frame: From Year 8 up to Year 9 ]
    SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject, or may have evolved into one of the outcomes listed above. Related SAE = SAE assessed by the investigator as causally related to the study vaccine administered in study HPV-014 (NCT00196937).
14. Number of Subjects With Any Fatal or Vaccine-related SAEs (Including SAEs Related to Study Procedures and GlaxoSmithKline Biologicals' Concomitant Medication) From Year 9 to Year 10 [ Time Frame: From Year 9 up to Year 10 ]
    SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject, or may have evolved into one of the outcomes listed above. Related SAE = SAE assessed by the investigator as causally related to the study vaccine administered in study HPV-014 (NCT00196937).
15. Number of Subjects With Any Fatal or Vaccine-related SAEs (Including SAEs Related to Study Procedures and GlaxoSmithKline Biologicals' Concomitant Medication) From Year 0 to Year 10 [ Time Frame: From Year 0 up to Year 10 ]
    SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject. Related SAE = SAE assessed by the investigator as causally related to the study vaccine administered in study HPV-014 (NCT00196937).

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 60 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Subjects who the investigator believed that they could and would comply with the requirements of the protocol.
• A female who had been enrolled in NCT00196937 study and received three doses of HPV-16/18 vaccine.
• Written informed consent obtained from the subject.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) or planned use during the study period.
• Chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs occurring less than three months prior to blood sampling.
• 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).
• Administration of immunoglobulins and/or any blood products within the three months preceding blood sampling.
• Administration or planned administration of any HPV vaccine, other than the three doses of HPV-16/18 vaccine administered in NCT00196937 study.

Contacts and Locations

Locations

Germany

GSK Investigational Site

Muenchen, Bayern, Germany, 80637

GSK Investigational Site

Wuerzburg, Bayern, Germany, 97070

GSK Investigational Site

Berlin, Germany, 12200

Poland

GSK Investigational Site

Bydgoszcz, Poland, 85-079

GSK Investigational Site

Poznan, Poland, 60-535

GSK Investigational Site

Poznan, Poland, 61-709

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Publications:

Schwarz T, Spaczynski M, Kaufmann A, Wysocki J, Gałaj A, Schulze K, Suryakiran P, Thomas F, Descamps D. Persistence of immune responses to the HPV-16/18 AS04-adjuvanted vaccine in women aged 15-55 years and first-time modelling of antibody responses in mature women: results from an open-label 6-year follow-up study. BJOG. 2015 Jan;122(1):107-18. doi: 10.1111/1471-0528.13070. Epub 2014 Sep 11.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00947115
• Other Study ID Numbers: 112772; 2009-011357-41 ( EudraCT Number )
• First Posted: July 27, 2009
• Results First Posted: May 2, 2011
• Last Update Posted: October 30, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• 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.
• URL: https://www.clinicalstudydatarequest.com/Posting.aspx?ID=4512

Keywords provided by GlaxoSmithKline:

Cervical cancer; HPV vaccine