HPV Infections
Conditions
Brief summary
A study to evaluate the efficacy, immunogenicity, safety and tolerability of V501 in adult women
Interventions
V501; Gardasil, 0.5 ml injection in 3 dosing regimen
BIOLOGICALComparator: Placebo
Placebo 0.5 ml injection in 3 dosing regimen
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 26 Years
Healthy volunteers
Yes
Inclusion criteria
* Female Subject Aged 18 To 26 Years * With 1-4 Lifetime Sexual Partners
Exclusion criteria
* Male Subject
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Combined Incidence of Persistent Human Papillomavirus (HPV) 6, 11, 16 and 18 Infection or HPV 6, 11, 16 and 18 Related-Disease as Determined by Clinical/Pathologic Criteria and Positive Polymerase Chain Reaction (PCR) Assay for Virus Subtype | Over 30 months | Participants with HPV 6, 11, 16 or 18 persistent infection, and genital disease (e.g., cervical, vaginal or vulval intraepithelial neoplasia, or cancer, adenocarcinoma in situ and genital warts) per 100 person-years of follow up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 6) | At one month after completed vaccination series (Month 7) | Month 7 HPV Competitive Luminex immunoassay (cLIA) Geometric Mean Titers (GMTs) by vaccine group. The limit of detection of the assay was 7 mMU/ml. GMTs and confidence limits below the limit of detection are shown as 7.0. |
| Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 11) | At one month after completed vaccination series (Month 7) | Month 7 HPV cLIA Geometric Mean Titers by vaccine group. The limit of detection of the assay was 8 mMU/ml. GMTs and confidence limits below the limit of detection are shown as 8.0. |
| Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 16) | At one month after completed vaccination series (Month 7) | Month 7 HPV cLIA Geometric Mean Titers by vaccine group. The limit of detection of the assay was 11 mMU/ml. GMTs and confidence limits below the limit of detection are shown as 11.0. |
| Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 18) | At one month after completed vaccination series (Month 7) | Month 7 HPV cLIA Geometric Mean Titers by vaccine group. The limit of detection of the assay was 10 mMU/ml. GMTs and confidence limits below the limit of detection are shown as 10.0. |
Participant flow
Recruitment details
Study was conducted at 14 sites in Japan from 2006 to 2009.
Pre-assignment details
There were no specific criteria.
Participants by arm
| Arm | Count |
|---|---|
| V501 V501; Gardasil, 0.5 mL intramuscular injection, in 3 dosing regimen, given at Day 1, Month 2, and Month 6 | 509 |
| Placebo Placebo 0.5 mL intramuscular injection, in 3 dosing regimen, given at Day 1, Month 2, and Month 6 | 512 |
| Total | 1,021 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Laboratory test values abnormal | 1 | 0 |
| Overall Study | Lost to Follow-up | 24 | 29 |
| Overall Study | Moved | 4 | 3 |
| Overall Study | Pregnancy | 7 | 5 |
| Overall Study | Protocol Violation | 2 | 0 |
| Overall Study | Withdrawal by Subject | 17 | 21 |
Baseline characteristics
| Characteristic | V501 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 22.7 years STANDARD_DEVIATION 2.1 | 22.9 years STANDARD_DEVIATION 2.1 | 22.8 years STANDARD_DEVIATION 2.1 |
| Body Weight | 52.1 Kilograms STANDARD_DEVIATION 8.2 | 51.7 Kilograms STANDARD_DEVIATION 7.3 | 51.9 Kilograms STANDARD_DEVIATION 7.8 |
| Sex: Female, Male Female | 509 Participants | 512 Participants | 1021 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 | 435 / 480 | 396 / 468 |
| serious Total, serious adverse events | 39 / 480 | 65 / 468 |
Outcome results
Primary
Combined Incidence of Persistent Human Papillomavirus (HPV) 6, 11, 16 and 18 Infection or HPV 6, 11, 16 and 18 Related-Disease as Determined by Clinical/Pathologic Criteria and Positive Polymerase Chain Reaction (PCR) Assay for Virus Subtype
Participants with HPV 6, 11, 16 or 18 persistent infection, and genital disease (e.g., cervical, vaginal or vulval intraepithelial neoplasia, or cancer, adenocarcinoma in situ and genital warts) per 100 person-years of follow up.
Time frame: Over 30 months
Population: Includes participants who were not general protocol violators, received all 3 vaccinations, and were seronegative at Day 1 and PCR negative through Month 7 for the relevant HPV type
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| V501 | Combined Incidence of Persistent Human Papillomavirus (HPV) 6, 11, 16 and 18 Infection or HPV 6, 11, 16 and 18 Related-Disease as Determined by Clinical/Pathologic Criteria and Positive Polymerase Chain Reaction (PCR) Assay for Virus Subtype | 0.4 Incidence per 100 person-years |
| Placebo | Combined Incidence of Persistent Human Papillomavirus (HPV) 6, 11, 16 and 18 Infection or HPV 6, 11, 16 and 18 Related-Disease as Determined by Clinical/Pathologic Criteria and Positive Polymerase Chain Reaction (PCR) Assay for Virus Subtype | 3.1 Incidence per 100 person-years |
95% CI: [59.2, 97.6]
Secondary
Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 11)
Month 7 HPV cLIA Geometric Mean Titers by vaccine group. The limit of detection of the assay was 8 mMU/ml. GMTs and confidence limits below the limit of detection are shown as 8.0.
Time frame: At one month after completed vaccination series (Month 7)
Population: Includes participants who were not general protocol violators, received all 3 vaccinations within acceptable day ranges, were seronegative at Day 1 for the relevant HPV type, and had a Month 7 serum sample collected within an acceptable time range
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| V501 | Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 11) | 579.8 Geometric Mean Titers |
| Placebo | Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 11) | 8.0 Geometric Mean Titers |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 16)
Month 7 HPV cLIA Geometric Mean Titers by vaccine group. The limit of detection of the assay was 11 mMU/ml. GMTs and confidence limits below the limit of detection are shown as 11.0.
Time frame: At one month after completed vaccination series (Month 7)
Population: Includes participants who were not general protocol violators, received all 3 vaccinations within acceptable day ranges, were seronegative at Day 1 for the relevant HPV type, and had a Month 7 serum sample collected within an acceptable time range
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| V501 | Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 16) | 2396.4 Geometric Mean Titers |
| Placebo | Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 16) | 11.0 Geometric Mean Titers |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 18)
Month 7 HPV cLIA Geometric Mean Titers by vaccine group. The limit of detection of the assay was 10 mMU/ml. GMTs and confidence limits below the limit of detection are shown as 10.0.
Time frame: At one month after completed vaccination series (Month 7)
Population: Includes participants who were not general protocol violators, received all 3 vaccinations within acceptable day ranges, were seronegative at Day 1 for the relevant HPV type, and had a Month 7 serum sample collected within an acceptable time range
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| V501 | Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 18) | 369.0 Geometric Mean Titers |
| Placebo | Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 18) | 10.0 Geometric Mean Titers |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 6)
Month 7 HPV Competitive Luminex immunoassay (cLIA) Geometric Mean Titers (GMTs) by vaccine group. The limit of detection of the assay was 7 mMU/ml. GMTs and confidence limits below the limit of detection are shown as 7.0.
Time frame: At one month after completed vaccination series (Month 7)
Population: Includes participants who were not general protocol violators, received all 3 vaccinations within acceptable day ranges, were seronegative at Day 1 for the relevant HPV type, and had a Month 7 serum sample collected within an acceptable time range
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| V501 | Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 6) | 390.8 Geometric Mean Titers |
| Placebo | Vaccine Type Serum Antibody Titer at One Month After Completed Vaccination Series (Anti-HPV 6) | 7.0 Geometric Mean Titers |
p-value: <0.001Wilcoxon (Mann-Whitney)