Human Papillomavirus Infection
Conditions
Brief summary
This study will evaluate the tolerability and immunogenicity of administration of the first dose of V503 at the same time as Menactra™ and Adacel™ versus administration of V503 one month prior to administration of Menactra™ and Adacel™.
Interventions
BIOLOGICALV503
V503 (Multivalent HPV L1 VLP vaccine) given as a 0.5 mL intramuscular injection in the deltoid muscle of the non-dominant arm at Day 1, Month 2, and Month 6
BIOLOGICALComparator: Menactra™ (Concomitant)
Menactra™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm on Day 1.
BIOLOGICALComparator: Adacel™ (Concomitant)
Adacel™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm on Day 1.
BIOLOGICALComparator: Menactra™ (Non-Concomitant)
Menactra™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm at Month 1.
BIOLOGICALComparator: Adacel™ (Non-concomitant)
Adacel™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm at Month 1.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
11 Years to 15 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject is in good health * Subject's parent/legal guardian can read, understand, and complete the vaccine report card * Subject is not sexually active and does not plan on becoming sexually active during the study * Subject has received a documented full primary immunization series against diphtheria, tetanus, and pertussis (not in the last 5 years)
Exclusion criteria
* Subject has a known allergy to any vaccine component of V503, Menactra™, or Adacel™ * Subject has a condition that is a contraindication to vaccination with Menactra™ or Adacel™ * Subject has any coagulation disorder * Female subject is pregnant * Subject is immunocompromised or immunodeficient * Subject has had a splenectomy * Subject has received immunosuppressive therapies in the prior year * Subject has received any immune globulin product or blood-derived product in the last 3 months * Subject has received inactivated vaccines within 14 days or live vaccines within 21 days of the first study vaccination * Subject has received a marketed HPV vaccine or has participation in an HPV vaccine trial * Subject has received a meningococcal vaccine * Subject has a fever \>= 100F within 24 hours of vaccination * Subject has a history of HPV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Maximum Temperature >=37.8 °C (>=100.0 °F) (Oral or Oral Equivalent) | Up to 5 days following the Day 1 and Month 1 vaccination / visit | For the Concomitant Vaccination group, temperatures were collected after the Day 1 vaccination and the Month 1 visit; for the Non-concomitant Vaccination group, temperatures were collected after the Day 1 vaccination and the Month 1 vaccination. |
| Percentage of Participants With a V503 Injection-site Adverse Experience | Day 1 through Day 5 following Day 1 vaccination | An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Only injection-site AEs in the arm that received V503 vaccination were reported for this endpoint. |
| Percentage of Participants With a Menactra™ or Adacel™ Injection-site Adverse Experience | Day 1 through Day 5 following Day 1 or Month 1 vaccination | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Only injection-site AEs in the arm that received Menactra™ and Adacel™ vaccination were reported for this endpoint. For the Concomitant Vaccination group, injection-site AEs are reported following Day 1 vaccination; for the Non-concomitant Vaccination group, injection-site AEs are reported following Month 1 vaccination. |
| Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | 4 weeks following Month 6 vaccination | Serum antibody titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 were evaluated using a competitive Luminex immunoassay. Titers are reported in milli Merck Units/mL. |
| Percentage of Participants With >=4-fold Increase in Antibody Titers to Neisseria Meningitidis Serogroups | Baseline and 4 weeks following Day 1 (Concomitant) or Month 1 (Non-concomitant) vaccination | For the Concomitant Vaccination group, serum samples were collected at Day 1 (baseline) and 4 weeks after the Day 1 vaccination; for the Non-concomitant Vaccination group, serum samples were collected at Month 1 (baseline) and 4 weeks after the Month 1 vaccination. Bactericidal antibodies to Neisseria meningitidis serogroups A, C, Y, and W-135 were measured by incubating serial dilutions of serum with target N. meningitidis strains and complement, and enumerating the surviving bacteria after overnight incubation on blood agar plates. The serum bactericidal titer is reported as the reciprocal of the final serum dilution giving \>50% killing in 60 minutes. |
| Percentage of Participants Who Achieve Acceptable Titers of Anti-Diphtheria and Anti-Tetanus Antibody | 4 weeks following Day 1 or Month 1 vaccination | For the Concomitant Vaccination group, serum samples were collected 4 weeks after the Day 1 vaccination; for the Non-concomitant Vaccination group, serum samples were collected 4 weeks after the Month 1 vaccination. Titers of neutralizing antibody to diphtheria toxin were measured using a cell-based Diphtheria Micrometabolic Inhibition assay. The lower limit of quantitation of the assay was defined as 0.01 International Units (IU)/mL. Serum titers of neutralizing antibody to tetanus toxin were measured using an enzyme immunoassay. The lower limit of quantitation of the assay was defined as 0.04 IU/mL. Acceptable titers refer to the World Health Organization-defined protective titers of \>=0.1 IU/mL. |
| Geometric Mean Titers of Pertussis Antibody Responses | 4 weeks following Day 1 or Month 1 vaccination | For the Concomitant Vaccination group, serum samples were collected 4 weeks after the Day 1 vaccination; for the Non-concomitant Vaccination group, serum samples were collected 4 weeks after the Month 1 vaccination. Titers of anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), anti-pertactin (PRN), and anti-fimbriae 2/3 (FM 2/3) antibodies were measured using enzyme-linked immunosorbent assays. The titers were expressed as Enzyme-linked Immunoassay Units (ELU)/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers of the Antibody Response to Neisseria Meningitidis Serogroups Contained in Menactra™ | 4 weeks following Day 1 or Month 1 vaccination | Serum bactericidal antibodies to Neisseria meningitidis serogroups A, C, Y, and W-135 were measured by incubating serial dilutions of serum with target N. meningitidis strains and complement, and enumerating the surviving bacteria after overnight incubation on blood agar plates. The antibody titer is expressed as the reciprocal of the highest dilution that achieves \>50% bacterial killing; a higher value represents a greater antibody response. For the Concomitant Vaccination group, serum samples were collected 4 weeks after Day 1 vaccination; for the Non-concomitant Vaccination group, serum samples were collected 4 weeks after Month 1 vaccination. |
| Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Month 7 | Blood was drawn at Month 7 and assayed to determine whether or not a participant had achieved seroconversion for the HPV types. The lower limit of the titer (milli Merck U/mL) considered seropositive was as follows: HPV Type 6: \>=30, HPV Type 11: \>=16; HPV Type 16: \>=20, HPV Type 18: \>=24, HPV Type 31: \>=10, HPV Type 33: \>=8, HPV Type 45: \>=8, HPV Type 52: \>=8, and HPV Type 58: \>=8. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Concomitant Vaccination V503 given as a 0.5 mL intramuscular injection in the deltoid muscle of the non-dominant arm on Day 1, Month 2, and Month 6, and Menactra™ and Adacel™ each given as a 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm on Day 1 | 621 |
| Non-concomitant Vaccination V503 given as a 0.5 mL intramuscular injection in the deltoid muscle of the non-dominant arm at Day 1, Month 2, and Month 6, and Menactra™ and Adacel™ each given as a 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm at Month 1 | 620 |
| Total | 1,241 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 20 | 16 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 15 | 18 |
Baseline characteristics
| Characteristic | Concomitant Vaccination | Non-concomitant Vaccination | Total |
|---|---|---|---|
| Age, Continuous | 12.2 Years STANDARD_DEVIATION 1.4 | 12.1 Years STANDARD_DEVIATION 1.3 | 12.2 Years STANDARD_DEVIATION 1.4 |
| Sex: Female, Male Female | 311 Participants | 310 Participants | 621 Participants |
| Sex: Female, Male Male | 310 Participants | 310 Participants | 620 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 543 / 613 | 518 / 611 |
| serious Total, serious adverse events | 5 / 613 | 5 / 611 |
Outcome results
Primary
Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503
Serum antibody titers to HPV Types 6, 11, 16, 18, 31, 33, 45, 52, and 58 were evaluated using a competitive Luminex immunoassay. Titers are reported in milli Merck Units/mL.
Time frame: 4 weeks following Month 6 vaccination
Population: The per-protocol population included participants who received all study vaccinations, were seronegative to HPV on Day 1, and had serum samples available for evaluation of the endpoint
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 11: n=502, 514 | 1495.0 milli Merck Units/mL |
| Concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 33: n=520, 537 | 1268.5 milli Merck Units/mL |
| Concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 18: n=516, 535 | 2610.4 milli Merck Units/mL |
| Concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 45: n=523, 539 | 947.8 milli Merck Units/mL |
| Concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 16: n=513, 530 | 8882.6 milli Merck Units/mL |
| Concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 52: n=521, 538 | 1082.7 milli Merck Units/mL |
| Concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 31: n=514, 536 | 2439.4 milli Merck Units/mL |
| Concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 58: n=519, 537 | 1532.8 milli Merck Units/mL |
| Concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 6: n=501, 514 | 2198.7 milli Merck Units/mL |
| Non-concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 58: n=519, 537 | 1555.1 milli Merck Units/mL |
| Non-concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 6: n=501, 514 | 2260.7 milli Merck Units/mL |
| Non-concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 11: n=502, 514 | 1547.2 milli Merck Units/mL |
| Non-concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 16: n=513, 530 | 9027.6 milli Merck Units/mL |
| Non-concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 18: n=516, 535 | 2633.9 milli Merck Units/mL |
| Non-concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 31: n=514, 536 | 2334.3 milli Merck Units/mL |
| Non-concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 33: n=520, 537 | 1276.3 milli Merck Units/mL |
| Non-concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 45: n=523, 539 | 863.8 milli Merck Units/mL |
| Non-concomitant Vaccination | Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503 | Anti-HPV 52: n=521, 538 | 1103.7 milli Merck Units/mL |
Comparison: Anti-HPV 6p-value: <0.00195% CI: [0.88, 1.08]ANOVA
Comparison: Anti-HPV 11p-value: <0.00195% CI: [0.87, 1.07]ANOVA
Comparison: Anti-HPV 16p-value: <0.00195% CI: [0.89, 1.09]ANOVA
Comparison: Anti-HPV 18p-value: <0.00195% CI: [0.88, 1.12]ANOVA
Comparison: Anti-HPV 31p-value: <0.00195% CI: [0.93, 1.17]ANOVA
Comparison: Anti-HPV 33p-value: <0.00195% CI: [0.89, 1.11]ANOVA
Comparison: Anti-HPV 45p-value: <0.00195% CI: [0.97, 1.25]ANOVA
Comparison: Anti-HPV 52p-value: <0.00195% CI: [0.88, 1.1]ANOVA
Comparison: Anti-HPV 58p-value: <0.00195% CI: [0.88, 1.1]ANOVA
Primary
Geometric Mean Titers of Pertussis Antibody Responses
For the Concomitant Vaccination group, serum samples were collected 4 weeks after the Day 1 vaccination; for the Non-concomitant Vaccination group, serum samples were collected 4 weeks after the Month 1 vaccination. Titers of anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), anti-pertactin (PRN), and anti-fimbriae 2/3 (FM 2/3) antibodies were measured using enzyme-linked immunosorbent assays. The titers were expressed as Enzyme-linked Immunoassay Units (ELU)/mL.
Time frame: 4 weeks following Day 1 or Month 1 vaccination
Population: The per-protocol population included participants who received study vaccination and had serum samples available for evaluation of the endpoint
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Concomitant Vaccination | Geometric Mean Titers of Pertussis Antibody Responses | Anti-PT: n=595, 566 | 28.5 ELU/mL |
| Concomitant Vaccination | Geometric Mean Titers of Pertussis Antibody Responses | Anti-FHA: n=595, 566 | 184.1 ELU/mL |
| Concomitant Vaccination | Geometric Mean Titers of Pertussis Antibody Responses | Anti-PRN: n=595, 566 | 328.4 ELU/mL |
| Concomitant Vaccination | Geometric Mean Titers of Pertussis Antibody Responses | Anti-FIM 2/3: n=595, 566 | 653.0 ELU/mL |
| Non-concomitant Vaccination | Geometric Mean Titers of Pertussis Antibody Responses | Anti-FIM 2/3: n=595, 566 | 681.4 ELU/mL |
| Non-concomitant Vaccination | Geometric Mean Titers of Pertussis Antibody Responses | Anti-PT: n=595, 566 | 35.7 ELU/mL |
| Non-concomitant Vaccination | Geometric Mean Titers of Pertussis Antibody Responses | Anti-PRN: n=595, 566 | 344.0 ELU/mL |
| Non-concomitant Vaccination | Geometric Mean Titers of Pertussis Antibody Responses | Anti-FHA: n=595, 566 | 201.4 ELU/mL |
Comparison: Anti-PTp-value: 0.00397.5% CI: [0.69, 0.92]ANOVA
Comparison: Anti-FHAp-value: <0.00197.5% CI: [0.83, 1.01]ANOVA
Comparison: Anti-PRNp-value: <0.00197.5% CI: [0.84, 1.08]ANOVA
Comparison: Anti-FIM 2/3p-value: <0.00197.5% CI: [0.76, 1.21]ANOVA
Primary
Percentage of Participants Who Achieve Acceptable Titers of Anti-Diphtheria and Anti-Tetanus Antibody
For the Concomitant Vaccination group, serum samples were collected 4 weeks after the Day 1 vaccination; for the Non-concomitant Vaccination group, serum samples were collected 4 weeks after the Month 1 vaccination. Titers of neutralizing antibody to diphtheria toxin were measured using a cell-based Diphtheria Micrometabolic Inhibition assay. The lower limit of quantitation of the assay was defined as 0.01 International Units (IU)/mL. Serum titers of neutralizing antibody to tetanus toxin were measured using an enzyme immunoassay. The lower limit of quantitation of the assay was defined as 0.04 IU/mL. Acceptable titers refer to the World Health Organization-defined protective titers of \>=0.1 IU/mL.
Time frame: 4 weeks following Day 1 or Month 1 vaccination
Population: The per-protocol population included participants who received study vaccination and had serum samples available for evaluation of the endpoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Concomitant Vaccination | Percentage of Participants Who Achieve Acceptable Titers of Anti-Diphtheria and Anti-Tetanus Antibody | Anti-diphtheria titer >=0.1 IU/mL: n=595, 566 | 100 Percentage of participants |
| Concomitant Vaccination | Percentage of Participants Who Achieve Acceptable Titers of Anti-Diphtheria and Anti-Tetanus Antibody | Anti-tetanus titer >=0.1 IU/mL: n=594, 562 | 99.8 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants Who Achieve Acceptable Titers of Anti-Diphtheria and Anti-Tetanus Antibody | Anti-diphtheria titer >=0.1 IU/mL: n=595, 566 | 100 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants Who Achieve Acceptable Titers of Anti-Diphtheria and Anti-Tetanus Antibody | Anti-tetanus titer >=0.1 IU/mL: n=594, 562 | 100 Percentage of participants |
Comparison: Anti-diphtheria titer \>=0.1 IU/mLp-value: <0.00197.5% CI: [-0.8, 0.9]Miettinen and Nurminen
Comparison: Anti-tetanus titer \>=0.1 IU/mLp-value: <0.00197.5% CI: [-1.2, 0.7]Miettinen and Nurminen
Primary
Percentage of Participants With >=4-fold Increase in Antibody Titers to Neisseria Meningitidis Serogroups
For the Concomitant Vaccination group, serum samples were collected at Day 1 (baseline) and 4 weeks after the Day 1 vaccination; for the Non-concomitant Vaccination group, serum samples were collected at Month 1 (baseline) and 4 weeks after the Month 1 vaccination. Bactericidal antibodies to Neisseria meningitidis serogroups A, C, Y, and W-135 were measured by incubating serial dilutions of serum with target N. meningitidis strains and complement, and enumerating the surviving bacteria after overnight incubation on blood agar plates. The serum bactericidal titer is reported as the reciprocal of the final serum dilution giving \>50% killing in 60 minutes.
Time frame: Baseline and 4 weeks following Day 1 (Concomitant) or Month 1 (Non-concomitant) vaccination
Population: The per-protocol population included participants who received study vaccination and had serum samples available for evaluation of the endpoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Concomitant Vaccination | Percentage of Participants With >=4-fold Increase in Antibody Titers to Neisseria Meningitidis Serogroups | Serogroup A: n=590, 564 | 79.0 Percentage of participants |
| Concomitant Vaccination | Percentage of Participants With >=4-fold Increase in Antibody Titers to Neisseria Meningitidis Serogroups | Serogroup C:n=590, 566 | 92.9 Percentage of participants |
| Concomitant Vaccination | Percentage of Participants With >=4-fold Increase in Antibody Titers to Neisseria Meningitidis Serogroups | Serogroup Y: n=590, 566 | 91.5 Percentage of participants |
| Concomitant Vaccination | Percentage of Participants With >=4-fold Increase in Antibody Titers to Neisseria Meningitidis Serogroups | Serogroup W-135: n=589, 566 | 95.6 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants With >=4-fold Increase in Antibody Titers to Neisseria Meningitidis Serogroups | Serogroup W-135: n=589, 566 | 97.7 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants With >=4-fold Increase in Antibody Titers to Neisseria Meningitidis Serogroups | Serogroup A: n=590, 564 | 75.4 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants With >=4-fold Increase in Antibody Titers to Neisseria Meningitidis Serogroups | Serogroup Y: n=590, 566 | 89.4 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants With >=4-fold Increase in Antibody Titers to Neisseria Meningitidis Serogroups | Serogroup C:n=590, 566 | 95.1 Percentage of participants |
Comparison: Serogroup Ap-value: <0.00197.5% CI: [-1.7, 9.3]Miettinen and Nurminen
Comparison: Serogroup Cp-value: <0.00197.5% CI: [-5.4, 1.1]Miettinen and Nurminen
Comparison: Serogroup Yp-value: <0.00197.5% CI: [-1.8, 6.1]Miettinen and Nurminen
Comparison: Serogroup W-135p-value: <0.00197.5% CI: [-4.7, 0.3]Miettinen and Nurminen
Primary
Percentage of Participants With a Menactra™ or Adacel™ Injection-site Adverse Experience
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Only injection-site AEs in the arm that received Menactra™ and Adacel™ vaccination were reported for this endpoint. For the Concomitant Vaccination group, injection-site AEs are reported following Day 1 vaccination; for the Non-concomitant Vaccination group, injection-site AEs are reported following Month 1 vaccination.
Time frame: Day 1 through Day 5 following Day 1 or Month 1 vaccination
Population: The population analyzed included all vaccinated participants with follow-up for injection-site AEs
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Concomitant Vaccination | Percentage of Participants With a Menactra™ or Adacel™ Injection-site Adverse Experience | 74.6 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants With a Menactra™ or Adacel™ Injection-site Adverse Experience | 70.7 Percentage of participants |
Primary
Percentage of Participants With a V503 Injection-site Adverse Experience
An adverse experience (AE) is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Only injection-site AEs in the arm that received V503 vaccination were reported for this endpoint.
Time frame: Day 1 through Day 5 following Day 1 vaccination
Population: The population analyzed included all vaccinated participants with follow-up for injection-site AEs
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Concomitant Vaccination | Percentage of Participants With a V503 Injection-site Adverse Experience | 59.9 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants With a V503 Injection-site Adverse Experience | 58.0 Percentage of participants |
Primary
Percentage of Participants With Maximum Temperature >=37.8 °C (>=100.0 °F) (Oral or Oral Equivalent)
For the Concomitant Vaccination group, temperatures were collected after the Day 1 vaccination and the Month 1 visit; for the Non-concomitant Vaccination group, temperatures were collected after the Day 1 vaccination and the Month 1 vaccination.
Time frame: Up to 5 days following the Day 1 and Month 1 vaccination / visit
Population: The population analyzed included all vaccinated participants with follow-up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Concomitant Vaccination | Percentage of Participants With Maximum Temperature >=37.8 °C (>=100.0 °F) (Oral or Oral Equivalent) | 7.7 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants With Maximum Temperature >=37.8 °C (>=100.0 °F) (Oral or Oral Equivalent) | 8.1 Percentage of participants |
p-value: 0.80695% CI: [-3.5, 2.7]Miettinen and Nurminen
Secondary
Geometric Mean Titers of the Antibody Response to Neisseria Meningitidis Serogroups Contained in Menactra™
Serum bactericidal antibodies to Neisseria meningitidis serogroups A, C, Y, and W-135 were measured by incubating serial dilutions of serum with target N. meningitidis strains and complement, and enumerating the surviving bacteria after overnight incubation on blood agar plates. The antibody titer is expressed as the reciprocal of the highest dilution that achieves \>50% bacterial killing; a higher value represents a greater antibody response. For the Concomitant Vaccination group, serum samples were collected 4 weeks after Day 1 vaccination; for the Non-concomitant Vaccination group, serum samples were collected 4 weeks after Month 1 vaccination.
Time frame: 4 weeks following Day 1 or Month 1 vaccination
Population: The per-protocol population included participants who received study vaccination and had serum samples available for evaluation of the endpoint
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Concomitant Vaccination | Geometric Mean Titers of the Antibody Response to Neisseria Meningitidis Serogroups Contained in Menactra™ | Serogroup A: n=595, 567 | 4832.7 Titer |
| Concomitant Vaccination | Geometric Mean Titers of the Antibody Response to Neisseria Meningitidis Serogroups Contained in Menactra™ | Serogroup C: n=595, 567 | 1002.8 Titer |
| Concomitant Vaccination | Geometric Mean Titers of the Antibody Response to Neisseria Meningitidis Serogroups Contained in Menactra™ | Serogroup Y: n=595, 567 | 1416.2 Titer |
| Concomitant Vaccination | Geometric Mean Titers of the Antibody Response to Neisseria Meningitidis Serogroups Contained in Menactra™ | Serogroup W-135: n=595, 567 | 3998.4 Titer |
| Non-concomitant Vaccination | Geometric Mean Titers of the Antibody Response to Neisseria Meningitidis Serogroups Contained in Menactra™ | Serogroup W-135: n=595, 567 | 3794.9 Titer |
| Non-concomitant Vaccination | Geometric Mean Titers of the Antibody Response to Neisseria Meningitidis Serogroups Contained in Menactra™ | Serogroup A: n=595, 567 | 4365.6 Titer |
| Non-concomitant Vaccination | Geometric Mean Titers of the Antibody Response to Neisseria Meningitidis Serogroups Contained in Menactra™ | Serogroup Y: n=595, 567 | 1066.7 Titer |
| Non-concomitant Vaccination | Geometric Mean Titers of the Antibody Response to Neisseria Meningitidis Serogroups Contained in Menactra™ | Serogroup C: n=595, 567 | 1068.4 Titer |
Secondary
Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503
Blood was drawn at Month 7 and assayed to determine whether or not a participant had achieved seroconversion for the HPV types. The lower limit of the titer (milli Merck U/mL) considered seropositive was as follows: HPV Type 6: \>=30, HPV Type 11: \>=16; HPV Type 16: \>=20, HPV Type 18: \>=24, HPV Type 31: \>=10, HPV Type 33: \>=8, HPV Type 45: \>=8, HPV Type 52: \>=8, and HPV Type 58: \>=8.
Time frame: Month 7
Population: The per-protocol population included participants who received all study vaccinations, were seronegative to HPV on Day 1, and had serum samples available for evaluation of the endpoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 16: n=513, 530 | 100.0 Percentage of participants |
| Concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 33: n=520, 537 | 100.0 Percentage of participants |
| Concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 11: n=502, 514 | 100.0 Percentage of participants |
| Concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 45: n=523, 539 | 100.0 Percentage of participants |
| Concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 18: n=516, 535 | 100.0 Percentage of participants |
| Concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 52: n=521, 538 | 100.0 Percentage of participants |
| Concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 6: n=501, 514 | 100.0 Percentage of participants |
| Concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 58: n=519, 537 | 100.0 Percentage of participants |
| Concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 31: n=514, 536 | 100.0 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 58: n=519, 537 | 100.0 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 11: n=502, 514 | 100.0 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 16: n=513, 530 | 100.0 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 18: n=516, 535 | 100.0 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 31: n=514, 536 | 100.0 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 33: n=520, 537 | 100.0 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 45: n=523, 539 | 100.0 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 52: n=521, 538 | 100.0 Percentage of participants |
| Non-concomitant Vaccination | Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503 | Anti-HPV 6: n=501, 514 | 100.0 Percentage of participants |