Clinical trial NCT00518336: Follow-up Study to Evaluate the Long-term Efficacy of the HPV Vaccine (580299) in Healthy Young Adult Women in Brazil
Official title: Follow-up Study to Evaluate the Long-term Efficacy of a HPV Vaccine (580299) in Healthy Young Adult Women in Brazil
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infections, Papillomavirus
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-08-20
Enrollment: 433
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. This Phase IIb study is designed to evaluate the the long-term efficacy, safety and immunogenicity of the 580299 HPV vaccine (CervarixTM) in a Brazilian cohort of women vaccinated in the phase IIb, blinded, primary study 580299/001 (NCT00689741) and having participated in follow-up study 580299/007 (NCT00120848). Only subjects who participated in the primary \& follow-up study will be enrolled in this long-term follow-up study. Subjects were aged 15-25 years at the time of entry into the primary study.

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

Detailed description: In this extension study, women who were vaccinated in the primary study, and participated in the follow-up study, will be followed with visits every 6 months.

Eligibility criteria: 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.
* Subjects who participated in study 580299-007.
* Written informed consent obtained from the subject prior to enrollment.

Exclusion Criteria:

* Use or planned use of any investigational or non-registered product other than the study vaccine.
* Decoding of the subject's 580299-001 treatment allocation to either the subject or the investigator.
* Administration or planned administration of any other HPV vaccine, other than the vaccine administered in study 580299-001.

Primary outcomes:
measure: Number of Subjects Presenting Cervical Infections With Human Papillomavirus (HPV) -16 and/or HPV-18
timeFrame: Up to year 8
measure: Number of Subjects Presenting Cervical Infections With Human Papillomavirus (HPV) -16 and/or HPV-18
timeFrame: Up to year 9
measure: Number of Subjects Presenting Cervical Infections With Human Papillomavirus (HPV) -16 and /or HPV-18
timeFrame: Up to year 7
Secondary outcomes:
measure: Number of Subjects Presenting Cervical Infections With Any Oncogenic HPV Type
timeFrame: Up to year 8
measure: Number of Subjects Presenting Cervical Infections With Individual Oncogenic Non-vaccine HPV Type
timeFrame: Up to year 8
measure: Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 and/or HPV-18
timeFrame: Up to year 8
measure: Number of Subjects With Persistent Infection (6-month Definition) With Any Oncogenic HPV Types
timeFrame: Up to year 8
measure: Number of Subjects With Persistent Infection (6-month Definition) With Individual Oncogenic Non-vaccine HPV Types
timeFrame: Up to year 8
measure: Number of Subjects With Persistent Infection (12-month Definition) With HPV-16 and/or HPV-18
timeFrame: Up to year 8
measure: Number of Subjects With Persistent Infection (12-month Definition) With Any Oncogenic HPV Types
timeFrame: Up to year 8
measure: Number of Subjects With Persistent Infection (12-month Definition) With Individual Oncogenic Non-vaccine HPV Types
timeFrame: Up to year 8
measure: Number of Subjects With Histopathologically-confirmed Cervical Intraepithelial Neoplasia (CIN)1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 8
measure: Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 8
measure: Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Individual Oncogenic Non-Vaccine HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 8
measure: Number of Subjects With Histopathologically-confirmed CIN2+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 8
measure: Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 8
measure: Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Individual Oncogenic Non-Vaccine HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 8
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With an HPV 16 and/or HPV-18 Cervical Infection
timeFrame: Up to year 8
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With Oncogenic HPV Types Cervical Infection
timeFrame: Up to year 8
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection
timeFrame: Up to year 8
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With an HPV 16 and/or HPV-18 Cervical Infection
timeFrame: Up to year 8
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Oncogenic HPV Types Cervical Infection
timeFrame: Up to year 8
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection
timeFrame: Up to year 8
measure: Anti-HPV-16 and Anti-HPV-18 Enzyme-linked Immunosorbent Assay (ELISA) Titers in the Immunogenicity Cohort
timeFrame: At Months 77-101
measure: Anti-HPV-16 and Anti-HPV-18 Pseudovirion-based Neutralization Assay (PBNA) Titers in the Immunogenicity Subset
timeFrame: At Months 77-101
measure: Number of Subjects With New Onset Chronic Diseases (NOCD) up to Year 7
timeFrame: Up to year 7
measure: Number of Subjects With NOCD up to Year 8
timeFrame: Up to year 8
measure: Number of Subjects With New Onset Autoimmune Disease (NOAD) up to Year 7
timeFrame: Up to year 7
measure: Number of Subjects With NOAD up to Year 8
timeFrame: Up to year 8
measure: Number of Subjects With Medically Significant Conditions up to Year 7
timeFrame: Up to year 7
measure: Number of Subjects With Medically Significant Conditions up to Year 8
timeFrame: up to year 8
measure: Number of Subjects With Serious Adverse Events (SAEs) up to Year 7
timeFrame: Up to year 7
measure: Number of Subjects With SAEs up to Year 8
timeFrame: up to year 8
measure: Number of Subjects Presenting Cervical Infections With Any Oncogenic HPV Type.
timeFrame: Up to year 9
measure: Number of Subjects Presenting Cervical Infections With Individual Oncogenic Non-vaccine HPV Type
timeFrame: Up to year 9
measure: Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 and/or HPV-18
timeFrame: Up to year 9
measure: Number of Subjects With Persistent Infection (6-month Definition) With Any Oncogenic HPV Type
timeFrame: Up to year 9
measure: Number of Subjects With Persistent Infection (6-month Definition) With Individual Oncogenic Non-vaccine HPV Types
timeFrame: Up to year 9
measure: Number of Subjects With Persistent Infection (12-month Definition) With HPV-16 and/or HPV-18
timeFrame: Up to year 9
measure: Number of Subjects With Persistent Infection (12-month Definition) With Any Oncogenic HPV Types
timeFrame: Up to year 9
measure: Number of Subjects With Persistent Infection (12-month Definition) With Individual Oncogenic Non-vaccine HPV Types
timeFrame: Up to year 9
measure: Number of Subjects With Histopathologically-confirmed CIN1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 9
measure: Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 9
measure: Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Individual Oncogenic Non-Vaccine HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 9
measure: Number of Subjects With Histopathologically-confirmed CIN2+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 9
measure: Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 9
measure: Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Individual Oncogenic Non-Vaccine HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 9
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undertermined Significance (ASC-US) Associated With an HPV 16 and/or HPV-18 Cervical Infection
timeFrame: Up to year 9
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undertermined Significance (ASC-US) Associated With Oncogenic HPV Types Cervical Infection
timeFrame: Up to year 9
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undertermined Significance (ASC-US) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection
timeFrame: Up to year 9
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With an HPV 16 and/or HPV-18 Cervical Infection
timeFrame: Up to year 9
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Oncogenic HPV Types Cervical Infection
timeFrame: Up to year 9
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection
timeFrame: Up to year 9
measure: Anti-HPV-16 and Anti-HPV-18 Enzyme-linked Immunosorbent Assay (ELISA) Titers in the Immunogenicity Cohort
timeFrame: At Month 77 until year 9 (Month 113)
measure: Anti-HPV-16 and Anti-HPV-18 Pseudovirion-based Neutralization Assay (PBNA) Titers in the Immunogenicity Subset
timeFrame: At Month 77 until year 9 (Month 113)
measure: Number of Subjects With New Onset Chronic Diseases (NOCD) up to Year 9
timeFrame: Up to year 9
measure: Number of Subjects With New Onset Autoimmune Disease (NOAD) up to Year 9.
timeFrame: Up to year 9
measure: Number of Subjects With Medically Signifant Conditions up to Year 9
timeFrame: Up to year 9
measure: Number of Subjects With Serious Adverse Events (SAEs) up to Year 9.
timeFrame: up to year 9
measure: Number of Subjects Presenting Cervical Infections With Any Oncogenic HPV Type.
timeFrame: Up to year 7
measure: Number of Subjects Presenting Cervical Infections With Individual Oncogenic Non-vaccine HPV Type.
timeFrame: Up to year 7
measure: Number of Subjects With Persistent Infection (6-month Definition) With HPV-16 and/or HPV-18
timeFrame: Up to year 7
measure: Number of Subjects With Persistent Infection (6-month Definition) With Any Oncogenic HPV Type
timeFrame: Up to year 7
measure: Number of Subjects With Persistent Infection (6-month Definition) With Individual Oncogenic Non-vaccine HPV Types
timeFrame: Up to year 7
measure: Number of Subjects With Persistent Infection (12-month Definition) With HPV-16 and/or HPV-18
timeFrame: Up to year 7
measure: Number of Subjects With Persistent Infection (12-month Definition) With Any Oncogenic HPV Type
timeFrame: Up to year 7
measure: Number of Subjects With Persistent Infection (12-month Definition) With Individual Oncogenic Non-vaccine HPV Types
timeFrame: Up to year 7
measure: Number of Subjects With Histopathologically-confirmed CIN1+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 7
measure: Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 7
measure: Number of Subjects With Histopathologically Confirmed CIN1+ Associated With Individual Oncogenic Non-Vaccine HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 7
measure: Number of Subjects With Histopathologically-confirmed CIN2+ Associated With HPV-16 or HPV-18 Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 7
measure: Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Oncogenic HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 7
measure: Number of Subjects With Histopathologically Confirmed CIN2+ Associated With Individual Oncogenic Non-Vaccine HPV Types Detected Within the Lesional Component of the Cervical Tissue Specimen
timeFrame: Up to year 7
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With an HPV 16 and/or HPV-18 Cervical Infection
timeFrame: Up to year 7
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With Oncogenic HPV Types Cervical Infection
timeFrame: Up to year 7
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Atypical Squamous Cells of Undetermined Significance (ASC-US) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection
timeFrame: Up to year 7
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With an HPV 16 and/or HPV-18 Cervical Infection
timeFrame: Up to year 7
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Oncogenic HPV Types Cervical Infection
timeFrame: Up to year 7
measure: Number of Subjects With Abnormal Cytology Greater Than or Equal to Low-grade Squamous Intraepithelial Lesion (LSIL) Associated With Individual Oncogenic Non-vaccine HPV Types Cervical Infection
timeFrame: Up to year 7
Other outcomes:
Locations:
city: Curitiba
country: Brazil
facility: GSK Investigational Site
state: Paraná
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: GSK Investigational Site
city: Fortaleza
country: Brazil
facility: GSK Investigational Site
city: São Paulo
country: Brazil
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Naud PS, Roteli-Martins CM, De Carvalho NS, Teixeira JC, de Borba PC, Sanchez N, Zahaf T, Catteau G, Geeraerts B, Descamps D. Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine: final analysis of a long-term follow-up study up to 9.4 years post-vaccination. Hum Vaccin Immunother. 2014;10(8):2147-62. doi: 10.4161/hv.29532.
citation: Roteli-Martins CM, Naud P, De Borba P, Teixeira JC, De Carvalho NS, Zahaf T, Sanchez N, Geeraerts B, Descamps D. Sustained immunogenicity and efficacy of the HPV-16/18 AS04-adjuvanted vaccine: up to 8.4 years of follow-up. Hum Vaccin Immunother. 2012 Mar;8(3):390-7. doi: 10.4161/hv.18865. Epub 2012 Feb 13.