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

Infections, Papillomavirus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00947115
• Other study ID #: 112772
• Secondary ID: 2009-011357-41
• Status: Completed
• Phase: Phase 3
• Start date: September 22, 2009
• Est. completion date: February 3, 2015

Study information

• Verified date: October 2020
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 525
• Est. completion date: February 3, 2015
• Est. primary completion date: February 3, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 20 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infections, Papillomavirus

Intervention

Procedure:
• Blood sampling
Blood samples were collected at Years 5, 6, 7, 8, 9 and 10.
• 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.

Locations

Country	Name	City	State
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Wuerzburg	Bayern
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Poznan

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Germany,  Poland, 

References & Publications (1)

Schwarz T, Spaczynski M, Kaufmann A, Wysocki J, Galaj 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anti-Human Papillomavirus (Anti-HPV)-16/18 Antibody Titers in Serum 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.	At Years 5, 6 and 7
Primary	Anti-HPV-16/18 Antibody Titers in Serum 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.	At Years 8, 9 and 10
Primary	Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies 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.	At Years 5, 6 and 7
Primary	Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies 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.	At Years 8, 9 and 10
Secondary	Anti-HPV-16/18 Secretion Antibody Titers in Cervico-vaginal Secretion (CVS) Samples at Years 5 and 6 in a Subset of Subjects	Anti-HPV-16/18 titers in CVS samples are presented as GMTs and expressed in EL.U/mL.	At Year 5 and Year 6
Secondary	Anti-HPV-16/18 Secretion Antibody Titers in CVS Samples at Years 7, 8, 9 and 10 in a Subset of Subjects	Anti-HPV-16/18 titers in CVS samples are presented as GMTs and expressed in EL.U/mL.	At Years 7, 8, 9 and 10
Secondary	Total Immunoglobulin G (IgG) Secretion Antibody Titers in CVS Samples at Years 5 and 6 in a Subset of Subjects	IgG antibody titers in CVS samples are presented as GMTs and expressed in microgram per milliliter (µg/mL).	At Year 5 and Year 6
Secondary	Total IgG Secretion Antibody Titers in CVS Samples at Years 7, 8, 9, and 10 in a Subset of Subjects	Total IgG antibody titers in CVS samples are presented as GMTs and expressed in microgram per milliliter (µg/mL).	At Years 7, 8, 9 and 10
Secondary	Total IgG Antibody Titers in Serum at Years 5, 6 and 7 Based on the ATP Cohort for Immunogenicity	Total IgG antibody titers are presented as GMTs and expressed in µg/mL.	At Years 5, 6 and 7
Secondary	Total IgG Antibody Titers in Serum at Years 8, 9 and 10 Based on the ATP Cohort for Immunogenicity	Total IgG antibody titers are presented as GMTs and expressed in µg/mL.	At Years 8, 9 and 10
Secondary	Total IgG Antibody Titers in Serum at Years 5, 6 and 7 Based on the TVC	Total IgG antibody titers are presented as GMTs and expressed in µg/mL.	At Years 5, 6 and 7
Secondary	Total IgG Antibody Titers in Serum at Years 8, 9 and 10 Based on the TVC	Total IgG antibody titers are presented as GMTs and expressed in µg/mL.	At Years 8, 9 and 10
Secondary	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	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).	From Year 4 in primary study HPV-014 (NCT00196937) up to Year 5 in present HPV-060 study
Secondary	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	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).	From Year 5 up to Year 6
Secondary	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	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).	From Year 6 up to Year 7
Secondary	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	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).	From Year 7 up to Year 8
Secondary	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	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).	From Year 8 up to Year 9
Secondary	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	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).	From Year 9 up to Year 10
Secondary	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	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).	From Year 0 up to Year 10