Trial Outcomes & Findings for Complementary Testing to Evaluate Immunogenicity of Human Papillomavirus (HPV) Vaccine (580299) in Healthy Female Subjects Aged >/= 26 Years (NCT NCT00456807)
NCT ID: NCT00456807
Last Updated: 2016-12-16
Results Overview
The geometric mean and 95% confidence interval of the number of Human Papilloma Virus type 16 (HPV-16) and HPV-18 specific CD4 and CD8 cells producing at least 2 different cytokines is reported per million of CD4 or CD8 T-cells, respectively.
COMPLETED
PHASE3
100 participants
At Month 12 and Month 18 after first vaccination
2016-12-16
Participant Flow
Subjects enrolled at pre-selected sites in the primary study HPV-015 (NCT00294047) who were in the immunogenicity subset and have received all three doses of vaccine/control were asked to participate in the present ancillary study.
This ancillary study will consist of supplemental testing of serological and cervical samples obtained at Visit 5 (Month 12) and Visit 6 (Month 18) of the primary study HPV-015 (NCT00294047) from pre-selected sites.
Participant milestones
| Measure |
Cervarix Group
Subjects who received 3 doses of Cervarix during the primary study (NCT00294047).
|
Placebo Group
Subjects who received 3 doses of placebo during the primary study (NCT00294047).
|
|---|---|---|
|
Overall Study
STARTED
|
53
|
47
|
|
Overall Study
COMPLETED
|
52
|
47
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Complementary Testing to Evaluate Immunogenicity of Human Papillomavirus (HPV) Vaccine (580299) in Healthy Female Subjects Aged >/= 26 Years
Baseline characteristics by cohort
| Measure |
Cervarix Group
n=53 Participants
Subjects who received 3 doses of Cervarix during the primary study (NCT00294047).
|
Placebo Group
n=47 Participants
Subjects who received 3 doses of placebo during the primary study (NCT00294047).
|
Total
n=100 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
40.9 years
STANDARD_DEVIATION 8.44 • n=5 Participants
|
40.3 years
STANDARD_DEVIATION 8.83 • n=7 Participants
|
40.6 years
STANDARD_DEVIATION 8.63 • n=5 Participants
|
|
Gender
Female
|
53 Participants
n=5 Participants
|
47 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
|
Gender
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At Month 12 and Month 18 after first vaccinationPopulation: Analysis was performed on subjects from the Total Vaccinated Cohort with available results.
The geometric mean and 95% confidence interval of the number of Human Papilloma Virus type 16 (HPV-16) and HPV-18 specific CD4 and CD8 cells producing at least 2 different cytokines is reported per million of CD4 or CD8 T-cells, respectively.
Outcome measures
| Measure |
Cervarix Group
n=52 Participants
Subjects who received 3 doses of Cervarix during the primary study (NCT00294047).
|
Placebo Group
n=47 Participants
Subjects who received 3 doses of placebo during the primary study (NCT00294047).
|
|---|---|---|
|
Number of Cytokine-positive CD4/CD8 Cells Per Million in Tests Producing at Least 2 Different Cytokines
HPV-16 specific CD4 [Month 12] (n=52,46)
|
877.4 cells per million CD4/CD8 T-cells
Interval 665.0 to 1157.7
|
19.5 cells per million CD4/CD8 T-cells
Interval 9.4 to 40.5
|
|
Number of Cytokine-positive CD4/CD8 Cells Per Million in Tests Producing at Least 2 Different Cytokines
HPV-16 specific CD4 [Month 18] (n=52,47)
|
738.5 cells per million CD4/CD8 T-cells
Interval 512.9 to 1063.3
|
22.3 cells per million CD4/CD8 T-cells
Interval 11.3 to 44.0
|
|
Number of Cytokine-positive CD4/CD8 Cells Per Million in Tests Producing at Least 2 Different Cytokines
HPV-16 specific CD8 [Month 12] (n=52,46)
|
2.0 cells per million CD4/CD8 T-cells
Interval 1.3 to 3.1
|
2.0 cells per million CD4/CD8 T-cells
Interval 1.2 to 3.1
|
|
Number of Cytokine-positive CD4/CD8 Cells Per Million in Tests Producing at Least 2 Different Cytokines
HPV-16 specific CD8 [Month 18] (n=50,47)
|
2.9 cells per million CD4/CD8 T-cells
Interval 1.8 to 4.7
|
2.7 cells per million CD4/CD8 T-cells
Interval 1.6 to 4.6
|
|
Number of Cytokine-positive CD4/CD8 Cells Per Million in Tests Producing at Least 2 Different Cytokines
HPV-18 specific CD4 [Month 12] (n=52,46)
|
581.2 cells per million CD4/CD8 T-cells
Interval 428.0 to 789.2
|
11.5 cells per million CD4/CD8 T-cells
Interval 5.7 to 23.4
|
|
Number of Cytokine-positive CD4/CD8 Cells Per Million in Tests Producing at Least 2 Different Cytokines
HPV-18 specific CD4 [Month 18] (n=52,47)
|
300.1 cells per million CD4/CD8 T-cells
Interval 171.9 to 524.1
|
16.8 cells per million CD4/CD8 T-cells
Interval 9.1 to 31.2
|
|
Number of Cytokine-positive CD4/CD8 Cells Per Million in Tests Producing at Least 2 Different Cytokines
HPV-18 specific CD8 [Month 12] (n=52,46)
|
2.1 cells per million CD4/CD8 T-cells
Interval 1.3 to 3.3
|
1.8 cells per million CD4/CD8 T-cells
Interval 1.1 to 2.7
|
|
Number of Cytokine-positive CD4/CD8 Cells Per Million in Tests Producing at Least 2 Different Cytokines
HPV-18 specific CD8 [Month 18] (n=50,47)
|
2.8 cells per million CD4/CD8 T-cells
Interval 1.7 to 4.6
|
4.7 cells per million CD4/CD8 T-cells
Interval 2.6 to 8.7
|
PRIMARY outcome
Timeframe: At Month 12 and Month 18 after first vaccinationPopulation: Analysis was performed on subjects from the Total Vaccinated Cohort with available results.
The geometric mean and 95% confidence interval of the number of HPV-16 and HPV-18 specific memory B-cells is reported per million of B-cells. An arbitrary value of 0 was given for subjects with antibody concentration below the limit of quantification.
Outcome measures
| Measure |
Cervarix Group
n=51 Participants
Subjects who received 3 doses of Cervarix during the primary study (NCT00294047).
|
Placebo Group
n=45 Participants
Subjects who received 3 doses of placebo during the primary study (NCT00294047).
|
|---|---|---|
|
Number of B-cells Per Million Showing a Specific Memory Response for HPV-16 and HPV-18
HPV-16 specific [Month 12] (n=51,44)
|
517.1 cells per million B-cells
Interval 361.4 to 739.9
|
101.4 cells per million B-cells
Interval 45.1 to 227.9
|
|
Number of B-cells Per Million Showing a Specific Memory Response for HPV-16 and HPV-18
HPV-16 specific [Month 18] (n=51,45)
|
304.4 cells per million B-cells
Interval 210.0 to 441.1
|
33.1 cells per million B-cells
Interval 6.7 to 163.0
|
|
Number of B-cells Per Million Showing a Specific Memory Response for HPV-16 and HPV-18
HPV-18 specific [Month 12] (n=51,44)
|
354.7 cells per million B-cells
Interval 253.1 to 497.1
|
68.4 cells per million B-cells
Interval 27.0 to 173.2
|
|
Number of B-cells Per Million Showing a Specific Memory Response for HPV-16 and HPV-18
HPV-18 specific [Month 18] (n=51,45)
|
301.5 cells per million B-cells
Interval 223.9 to 406.0
|
0.0 cells per million B-cells
Interval 0.0 to 0.0
|
PRIMARY outcome
Timeframe: At Month 12 and Month 18 after first vaccinationPopulation: Analysis was performed on subjects from the Total Vaccinated Cohort with available results.
Cut-off values assessed include 8 enzyme-linked immunosorbent assay units Per Milliliter (EL.U/mL)for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.
Outcome measures
| Measure |
Cervarix Group
n=52 Participants
Subjects who received 3 doses of Cervarix during the primary study (NCT00294047).
|
Placebo Group
n=46 Participants
Subjects who received 3 doses of placebo during the primary study (NCT00294047).
|
|---|---|---|
|
Number of Subjects With Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations Above Pre-defined Cut-off Values
Anti-HPV-16 [Month 12] (n=52, 45)
|
52 Subjects
|
14 Subjects
|
|
Number of Subjects With Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations Above Pre-defined Cut-off Values
Anti-HPV-16 [Month 18] (n=49, 46)
|
49 Subjects
|
14 Subjects
|
|
Number of Subjects With Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations Above Pre-defined Cut-off Values
Anti-HPV-18 [Month 12] (n=52, 45)
|
52 Subjects
|
7 Subjects
|
|
Number of Subjects With Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations Above Pre-defined Cut-off Values
Anti-HPV-18 [Month 18] (n=49, 46)
|
49 Subjects
|
7 Subjects
|
PRIMARY outcome
Timeframe: At Month 12 and Month 18 after first vaccinationPopulation: Analysis was performed on subjects from the Total Vaccinated Cohort with available results.
Titers are presented as Geometric Mean Titers (GMTs).
Outcome measures
| Measure |
Cervarix Group
n=52 Participants
Subjects who received 3 doses of Cervarix during the primary study (NCT00294047).
|
Placebo Group
n=46 Participants
Subjects who received 3 doses of placebo during the primary study (NCT00294047).
|
|---|---|---|
|
Titers of Anti-HPV-16 and Anti-HPV-18 Antibodies
Anti-HPV-16 [Month 12] (n=52, 45)
|
2050.4 Titer
Interval 1456.1 to 2887.3
|
6.9 Titer
Interval 5.3 to 9.0
|
|
Titers of Anti-HPV-16 and Anti-HPV-18 Antibodies
Anti-HPV-16 [Month 18] (n=49, 46)
|
1517.1 Titer
Interval 1067.4 to 2156.4
|
7.2 Titer
Interval 5.4 to 9.5
|
|
Titers of Anti-HPV-16 and Anti-HPV-18 Antibodies
Anti-HPV-18 [Month 12] (n=52, 45)
|
761.4 Titer
Interval 538.0 to 1077.5
|
4.8 Titer
Interval 3.5 to 6.7
|
|
Titers of Anti-HPV-16 and Anti-HPV-18 Antibodies
Anti-HPV-18 [Month 18] (n=49, 46)
|
551.4 Titer
Interval 387.5 to 784.6
|
4.9 Titer
Interval 3.6 to 6.6
|
PRIMARY outcome
Timeframe: At Month 12 and Month 18 after first vaccinationPopulation: Analysis was performed on the Total Vaccinated Cohort, on subjects with available data. None of the subjects in the Placebo Group had detectable antibodies against HPV-16 at Months 12 and 18 and against HPV-18 at Month 12.
Titers given as Geometric Mean Titers (GMTs). An arbitrary value of 0 was given for subjects with antibody concentration below the limit of quantification.
Outcome measures
| Measure |
Cervarix Group
n=26 Participants
Subjects who received 3 doses of Cervarix during the primary study (NCT00294047).
|
Placebo Group
n=20 Participants
Subjects who received 3 doses of placebo during the primary study (NCT00294047).
|
|---|---|---|
|
Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) Immunoglobulin G (IgG) Antibodies
Anti-HPV16 [Month 12] (n=12, 10)
|
129.5 Titer
Interval 58.0 to 289.2
|
0 Titer
Interval 0.0 to 0.0
|
|
Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) Immunoglobulin G (IgG) Antibodies
Anti-HPV16 [Month 18] (n=26, 20)
|
99.9 Titer
Interval 48.9 to 203.8
|
0 Titer
Interval 0.0 to 0.0
|
|
Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) Immunoglobulin G (IgG) Antibodies
Anti-HPV18 [Month 12] (n=12, 10)
|
67.2 Titer
Interval 28.6 to 158.0
|
0 Titer
Interval 0.0 to 0.0
|
|
Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) Immunoglobulin G (IgG) Antibodies
Anti-HPV18 [Month 18] (n=26, 20)
|
42.8 Titer
Interval 23.1 to 79.6
|
5.8 Titer
Interval 5.8 to 5.8
|
PRIMARY outcome
Timeframe: At Month 12 and Month 18 after first vaccinationPopulation: Analysis was performed on the Total Vaccinated Cohort, only on those subjects from the Cervarix group with CVS sample results available.
Pearson coefficients of correlation between serum and CVS for anti-HPV-16 and anti-HPV-18 titers standardized for total IgG were calculated.
Outcome measures
| Measure |
Cervarix Group
n=26 Participants
Subjects who received 3 doses of Cervarix during the primary study (NCT00294047).
|
Placebo Group
Subjects who received 3 doses of placebo during the primary study (NCT00294047).
|
|---|---|---|
|
Correlation of Anti-HPV-16 and Anti-HPV-18 Antibodies in Serum and in Cervical Secretion (CVS) Samples
Anti-HPV-18 (Month 12)
|
0.901 correlation coefficient
|
—
|
|
Correlation of Anti-HPV-16 and Anti-HPV-18 Antibodies in Serum and in Cervical Secretion (CVS) Samples
Anti-HVP-16 (Month 12)
|
0.903 correlation coefficient
|
—
|
|
Correlation of Anti-HPV-16 and Anti-HPV-18 Antibodies in Serum and in Cervical Secretion (CVS) Samples
Anti- HPV-16 (Month 18)
|
0.898 correlation coefficient
|
—
|
|
Correlation of Anti-HPV-16 and Anti-HPV-18 Antibodies in Serum and in Cervical Secretion (CVS) Samples
Anti-HPV-18 (Month 18)
|
0.876 correlation coefficient
|
—
|
Adverse Events
Cervarix Group
Placebo Group
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER