Cervical Intraepithelial Neoplasia, Papillomavirus Infection
Conditions
Keywords
Prophylaxis HPV-16/18 infections and cervical neoplasia
Brief summary
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.
Interventions
BIOLOGICALGSK Biologicals' HPV-16/18 Vaccine (Cervarix™)
Three doses of vaccine administrerd intramuscularly according to 0, 1, 6 month schedule
BIOLOGICALHavrix™
Three doses of vaccine administrerd intramuscularly according to 0, 1, 6 month schedule.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
10 Years to 14 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | At 18, 24, 36 and 48 months | Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Titers of Anti-3-O-desacyl-4'-Monophosphoryl Lipid A (Anti-MPL) Antibodies During the Initial 2 Years Follow-up | At Months 18 and 24 | Titers are given as Geometric Mean Titers (GMTs) expressed as EL.U/mL. |
| Titers of Anti-3-O-desacyl 4'-Monophosphoryl Lipid A (Anti-MPL) Antibodies During the Last 2 Years Follow-up | At Month 36 and 48 | Titers are given as Geometric Mean Titers (GMTs) expressed as EL.U/mL. |
| 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 | From Month 18 to Month 24 | 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. |
| 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 | From Month 24 to Month 48 | 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. |
Countries
Colombia, Germany, Honduras, Panama, Taiwan
Participant flow
Pre-assignment details
Subjects from the Cervarix group continued the long-term follow-up study until Month 48 while subjects from the Havrix group completed the study at Month 24.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 626 |
| 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. | 619 |
| Total | 1,245 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 38 | 48 |
Baseline characteristics
| Characteristic | Cervarix Group | Havrix Group | Total |
|---|---|---|---|
| Age Continuous | 12.1 years STANDARD_DEVIATION 1.4 | 12.1 years STANDARD_DEVIATION 1.4 | 12.1 years STANDARD_DEVIATION 1.4 |
| Sex: Female, Male Female | 626 Participants | 619 Participants | 1245 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 626 | 0 / 619 |
| serious Total, serious adverse events | 33 / 626 | 5 / 619 |
Outcome results
Primary
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).
Time frame: At 18, 24, 36 and 48 months
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity, on those subjects from the Cervarix Group with available data for the defined time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-16 at Month 18 (n= 588) | 3901.6 EL.U/mL |
| Cervarix Group | Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-16 at Month 24 (n= 549) | 3226.3 EL.U/mL |
| Cervarix Group | Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-16 at Month 36 (n= 571) | 2688.6 EL.U/mL |
| Cervarix Group | Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-16 at Month 48 (n= 559) | 2395.8 EL.U/mL |
| Cervarix Group | Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-18 at Month 18 (n= 587) | 1570.8 EL.U/mL |
| Cervarix Group | Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-18 at Month 48 (n= 559) | 885.6 EL.U/mL |
| Cervarix Group | Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-18 at Month 24 (n= 548) | 1263.4 EL.U/mL |
| Cervarix Group | Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies | Anti-HPV-18 at Month 36 (n= 570) | 995.0 EL.U/mL |
Secondary
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.
Time frame: From Month 24 to Month 48
Population: Analyses were performed on the Total Vaccinated Cohort, on subjects with available data at the defined time point. Analysis was only done for subjects in the Cervarix Group, as all subjects from the Havrix Group completed the study at Month 24.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | 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 | ER visits (Month 36 to 48) (n=588,0) | 50 Subjects |
| Cervarix Group | 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 | Pregnancies (Month 24 to 36) (n=626,0) | 3 Subjects |
| Cervarix Group | 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 | Pregnancies (Month 36 to 48) (n=588,0) | 11 Subjects |
| Cervarix Group | 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 | NOCDs (Month 24 to 36) (n=601,0) | 7 Subjects |
| Cervarix Group | 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 | NOCDs (Month 36 to 48) (n=588,0) | 6 Subjects |
| Cervarix Group | 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 | ER visits (Month 24 to 36) (n=601,0) | 41 Subjects |
| Cervarix Group | 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 | SAEs (Month 24 to 36) (n=601,0) | 10 Subjects |
| Cervarix Group | 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 | SAEs (Month 36 to 48) (n=588,0) | 15 Subjects |
Secondary
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.
Time frame: From Month 18 to Month 24
Population: Analyses were performed on the Total Vaccinated Cohort, on subjects with available data at the defined time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cervarix Group | 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 | Pregnancies (n=626, 619) | 8 Subjects |
| Cervarix Group | 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 | NOCDs (n=617, 571) | 5 Subjects |
| Cervarix Group | 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 (n=617, 571) | 8 Subjects |
| Cervarix Group | 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 | ER visits (n=617, 571) | 40 Subjects |
| Havrix Group | 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 (n=617, 571) | 5 Subjects |
| Havrix Group | 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 | NOCDs (n=617, 571) | 3 Subjects |
| Havrix Group | 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 | ER visits (n=617, 571) | 21 Subjects |
| Havrix Group | 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 | Pregnancies (n=626, 619) | 1 Subjects |
Secondary
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.
Time frame: At Months 18 and 24
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data for the defined time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | Titers of Anti-3-O-desacyl-4'-Monophosphoryl Lipid A (Anti-MPL) Antibodies During the Initial 2 Years Follow-up | Month 18 (n= 128, 129) | 347.2 EL.U/mL |
| Cervarix Group | Titers of Anti-3-O-desacyl-4'-Monophosphoryl Lipid A (Anti-MPL) Antibodies During the Initial 2 Years Follow-up | Month 24 (n= 551, 338) | 271.5 EL.U/mL |
| Havrix Group | Titers of Anti-3-O-desacyl-4'-Monophosphoryl Lipid A (Anti-MPL) Antibodies During the Initial 2 Years Follow-up | Month 18 (n= 128, 129) | 117.7 EL.U/mL |
| Havrix Group | Titers of Anti-3-O-desacyl-4'-Monophosphoryl Lipid A (Anti-MPL) Antibodies During the Initial 2 Years Follow-up | Month 24 (n= 551, 338) | 74.0 EL.U/mL |
Secondary
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.
Time frame: At Month 36 and 48
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available data for the defined time point. Analysis was only done for subjects in the Cervarix Group, as all subjects from the Havrix Group completed the study at Month 24.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cervarix Group | Titers of Anti-3-O-desacyl 4'-Monophosphoryl Lipid A (Anti-MPL) Antibodies During the Last 2 Years Follow-up | Month 36 (n= 571) | 224.7 EL.U/mL |
| Cervarix Group | Titers of Anti-3-O-desacyl 4'-Monophosphoryl Lipid A (Anti-MPL) Antibodies During the Last 2 Years Follow-up | Month 48 (n= 558) | 170.0 EL.U/mL |