Cervical Cancer, Genital Warts, Human Papillomavirus Infection, Vaginal Cancer, Vulvar Cancer
Conditions
Brief summary
This study will assess the safety and immunogenicity of GARDASIL®9 (V503) in 16- to 45-year-old women. The primary hypothesis of the study states that anti-HPV 16, 18, 31, 33, 45, 52, and 58 geometric mean titers (GMTs) at 4 weeks postdose 3 are non-inferior in adult women as compared with GMTs in young adult women.
Interventions
BIOLOGICALV503
V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* good physical health
Exclusion criteria
* history of an abnormal Pap (Papanicolaou) test or abnormal cervical biopsy results * history of HPV-related condition * history of known prior vaccination with an HPV vaccine * pregnant * user of recreational or illicit drugs * history of severe allergic reaction, including known allergy to any vaccine component * immunocompromised * history of certain medications or is currently taking or has taken certain medications (details will be discussed at the time of consent) * has thrombocytopenia or other coagulation disorder * concurrently enrolled in a clinical study of investigational agent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | 4 weeks post vaccination 3 (Month 7) | Antibodies to the HPV types contained in V503 were measured using a competitive luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). Statistical comparisons between arms was performed for the HPV types considered oncogenic (HPV Types 16/18/31/33/45/52/58). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Had Study Vaccine Discontinued Due to Adverse Event. | Up to 1 month post vaccination 3 (up to 7 months) | An adverse event is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The percentage of participants who discontinued the study vaccine due to an adverse event regardless of study completion status was assessed. |
| Percentage of Participants With at Least 1 Solicited Injection-site Adverse Event | Up to 5 days post any vaccination | Participants were asked to record any injection-site reactions prompted in the Vaccination Report Card, i.e., injection-site tenderness, swelling, or redness, occurring after each study vaccination (solicited injection-site reactions). The percentage of participants with 1 or more solicited injection-site AE was assessed. |
| Percentage of Participants That Experienced at Least 1 Adverse Event (AE) | Up to 1 month post vaccination 3 (up to 7 months) | An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants with 1 or more AEs was assessed. |
| Percentage of Participants With Elevated Temperature (Fever) | Up to 5 days post any vaccination | Participants were asked to record oral body temperature in the Vaccination Report Card. The percentage of participants with elevated temperature (≥37.8°C or 100.0°F) was assessed. |
| Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | 4 weeks post vaccination 3 (Month 7) | Antibodies to the HPV types contained in V503 were measured using a competitive luminex immunoassay. The percentage of participants who were seronegative on Day 1 and have anti-HPV titer greater or equal to the type-specific serostatus cutoff at 4 weeks postdose 3 was assessed. |
| Percentage of Participants That Reported at Least 1 Systemic Adverse Event | Up to 15 days post any vaccination | An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. Systemic AEs are those not categorized as injection-site AEs. The percentage of participants that reported at least 1 systemic AE was assessed |
Countries
Austria, Belgium, Finland, Germany, Italy, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Women 16-26 Years of Age Young adult women 16- to 26-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6. | 570 |
| Women 27-45 Years of Age Adult women 27- to 45-years old received V503 vaccination, 0.5 mL in a 3-dose regimen administered on Day 1, Month 2, and Month 6. | 642 |
| Total | 1,212 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 8 | 5 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Screen Failure | 0 | 1 |
| Overall Study | Status unknown | 0 | 1 |
| Overall Study | Withdrawal by Subject | 8 | 9 |
Baseline characteristics
| Characteristic | Women 16-26 Years of Age | Women 27-45 Years of Age | Total |
|---|---|---|---|
| Age, Continuous | 21.6 years STANDARD_DEVIATION 2.8 | 35.8 years STANDARD_DEVIATION 5.5 | 29.1 years STANDARD_DEVIATION 8.3 |
| Race American Indian or Alaska Native | 2 Participants | 1 Participants | 3 Participants |
| Race Asian | 17 Participants | 10 Participants | 27 Participants |
| Race Black or African American | 5 Participants | 3 Participants | 8 Participants |
| Race Multiple | 7 Participants | 1 Participants | 8 Participants |
| Race White | 539 Participants | 627 Participants | 1166 Participants |
| Race/Ethnicity, Customized Hispanic | 21 Participants | 7 Participants | 28 Participants |
| Race/Ethnicity, Customized Not Hispanic | 548 Participants | 634 Participants | 1182 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 570 Participants | 642 Participants | 1212 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 | 0 / 570 | 0 / 640 |
| other Total, other adverse events | 518 / 570 | 574 / 640 |
| serious Total, serious adverse events | 6 / 570 | 8 / 640 |
Outcome results
Primary
Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type
Antibodies to the HPV types contained in V503 were measured using a competitive luminex immunoassay. Antibody titers were expressed as milli Merck units/mL (mMU/mL). Statistical comparisons between arms was performed for the HPV types considered oncogenic (HPV Types 16/18/31/33/45/52/58).
Time frame: 4 weeks post vaccination 3 (Month 7)
Population: Received all 3 vaccinations of the correct dose and within acceptable day ranges, had evaluable serology results at Day 1 and Month 7, must have been seronegative to the appropriate HPV type at Day 1 and had no protocol deviations that could interfere with the evaluation of participant's immune response to the 9vHPV vaccine.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Women 16-26 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 11 | 598.7 mMU/mL |
| Women 16-26 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 33 | 354.5 mMU/mL |
| Women 16-26 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 18 | 744.5 mMU/mL |
| Women 16-26 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 45 | 214.9 mMU/mL |
| Women 16-26 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 16 | 3075.8 mMU/mL |
| Women 16-26 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 52 | 346.5 mMU/mL |
| Women 16-26 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 31 | 596.1 mMU/mL |
| Women 16-26 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 58 | 428.0 mMU/mL |
| Women 16-26 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 6 | 787.8 mMU/mL |
| Women 27-45 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 58 | 296.4 mMU/mL |
| Women 27-45 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 6 | 638.4 mMU/mL |
| Women 27-45 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 11 | 453.5 mMU/mL |
| Women 27-45 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 16 | 2147.5 mMU/mL |
| Women 27-45 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 18 | 532.1 mMU/mL |
| Women 27-45 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 31 | 395.7 mMU/mL |
| Women 27-45 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 33 | 259.0 mMU/mL |
| Women 27-45 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 45 | 145.6 mMU/mL |
| Women 27-45 Years of Age | Anti-HPV Geometric Mean Titers (GMTs) for Each Anti-HPV Type | Anti-HPV 52 | 244.7 mMU/mL |
Comparison: Anti HPV 16p-value: <0.00195% CI: [0.63, 0.77]ANOVA
Comparison: Anti HPV 18p-value: <0.00195% CI: [0.64, 0.8]ANOVA
Comparison: Anti HPV 31p-value: <0.00195% CI: [0.6, 0.74]ANOVA
Comparison: Anti HPV 33p-value: <0.00195% CI: [0.67, 0.8]ANOVA
Comparison: Anti HPV 45p-value: <0.00195% CI: [0.6, 0.76]ANOVA
Comparison: Anti HPV 52p-value: <0.00195% CI: [0.64, 0.78]ANOVA
Comparison: Anti HPV 58p-value: <0.00195% CI: [0.63, 0.76]ANOVA
Secondary
Percentage of Participants That Experienced at Least 1 Adverse Event (AE)
An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants with 1 or more AEs was assessed.
Time frame: Up to 1 month post vaccination 3 (up to 7 months)
Population: All participants that received at least 1 vaccination and had available data for endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women 16-26 Years of Age | Percentage of Participants That Experienced at Least 1 Adverse Event (AE) | 92.8 Percentage of Participants |
| Women 27-45 Years of Age | Percentage of Participants That Experienced at Least 1 Adverse Event (AE) | 92.5 Percentage of Participants |
Secondary
Percentage of Participants That Reported at Least 1 Systemic Adverse Event
An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. Systemic AEs are those not categorized as injection-site AEs. The percentage of participants that reported at least 1 systemic AE was assessed
Time frame: Up to 15 days post any vaccination
Population: All participants that received at least 1 vaccination and had available data for endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women 16-26 Years of Age | Percentage of Participants That Reported at Least 1 Systemic Adverse Event | 66.3 Percentage of Participants |
| Women 27-45 Years of Age | Percentage of Participants That Reported at Least 1 Systemic Adverse Event | 64.4 Percentage of Participants |
95% CI: [-7.3, 3.4]
Secondary
Percentage of Participants Who Had Study Vaccine Discontinued Due to Adverse Event.
An adverse event is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The percentage of participants who discontinued the study vaccine due to an adverse event regardless of study completion status was assessed.
Time frame: Up to 1 month post vaccination 3 (up to 7 months)
Population: All participants that received at least 1 vaccination and had available data for endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women 16-26 Years of Age | Percentage of Participants Who Had Study Vaccine Discontinued Due to Adverse Event. | 0.0 Percentage of Participants |
| Women 27-45 Years of Age | Percentage of Participants Who Had Study Vaccine Discontinued Due to Adverse Event. | 0.2 Percentage of Participants |
Secondary
Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types
Antibodies to the HPV types contained in V503 were measured using a competitive luminex immunoassay. The percentage of participants who were seronegative on Day 1 and have anti-HPV titer greater or equal to the type-specific serostatus cutoff at 4 weeks postdose 3 was assessed.
Time frame: 4 weeks post vaccination 3 (Month 7)
Population: Received all 3 vaccinations of the correct dose and within acceptable day ranges, had evaluable serology results at Day 1 and Month 7, must have been seronegative to the appropriate HPV type at Day 1 and had no protocol deviations that could interfere with the evaluation of participant's immune response to the 9vHPV vaccine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Women 16-26 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 11 | 100.0 Percentage of Participants |
| Women 16-26 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 33 | 100.0 Percentage of Participants |
| Women 16-26 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 18 | 100.0 Percentage of Participants |
| Women 16-26 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 45 | 99.6 Percentage of Participants |
| Women 16-26 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 16 | 100.0 Percentage of Participants |
| Women 16-26 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 52 | 100.0 Percentage of Participants |
| Women 16-26 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 31 | 100.0 Percentage of Participants |
| Women 16-26 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 58 | 100.0 Percentage of Participants |
| Women 16-26 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 6 | 99.8 Percentage of Participants |
| Women 27-45 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 58 | 99.8 Percentage of Participants |
| Women 27-45 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 6 | 100.0 Percentage of Participants |
| Women 27-45 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 11 | 99.8 Percentage of Participants |
| Women 27-45 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 16 | 100.0 Percentage of Participants |
| Women 27-45 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 18 | 99.6 Percentage of Participants |
| Women 27-45 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 31 | 99.8 Percentage of Participants |
| Women 27-45 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 33 | 99.8 Percentage of Participants |
| Women 27-45 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 45 | 99.2 Percentage of Participants |
| Women 27-45 Years of Age | Percentage of Participants Who Seroconverted to Each of the Anti-HPV Types | Anti HPV 52 | 100.0 Percentage of Participants |
Secondary
Percentage of Participants With at Least 1 Solicited Injection-site Adverse Event
Participants were asked to record any injection-site reactions prompted in the Vaccination Report Card, i.e., injection-site tenderness, swelling, or redness, occurring after each study vaccination (solicited injection-site reactions). The percentage of participants with 1 or more solicited injection-site AE was assessed.
Time frame: Up to 5 days post any vaccination
Population: All participants that received at least 1 vaccination and had available data for endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women 16-26 Years of Age | Percentage of Participants With at Least 1 Solicited Injection-site Adverse Event | 87.2 Percentage of Participants |
| Women 27-45 Years of Age | Percentage of Participants With at Least 1 Solicited Injection-site Adverse Event | 84.7 Percentage of Participants |
p-value: 0.21295% CI: [-6.4, 1.4]Miettinen & Nurminen
Secondary
Percentage of Participants With Elevated Temperature (Fever)
Participants were asked to record oral body temperature in the Vaccination Report Card. The percentage of participants with elevated temperature (≥37.8°C or 100.0°F) was assessed.
Time frame: Up to 5 days post any vaccination
Population: All participants that received at least 1 vaccination and had available data for endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Women 16-26 Years of Age | Percentage of Participants With Elevated Temperature (Fever) | 3.5 Percentage of Participants |
| Women 27-45 Years of Age | Percentage of Participants With Elevated Temperature (Fever) | 2.5 Percentage of Participants |
p-value: 0.395% CI: [-3.1, 0.9]Miettinen & Nurminen