A Study of V503 Given Concomitantly With Menactra™ and Adacel™ in 11 to 15 Year Olds (V503-005)

Study Overview
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Brief Summary
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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™.

Official Title
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A Phase III Open-Label Clinical Trial to Study the Immunogenicity and Tolerability of V503 (A Multivalent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] Vaccine) Given Concomitantly With Menactra™ and Adacel™ in Preadolescents and Adolescents (11 to 15 Year Olds)

Conditions
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Human Papillomavirus Infection

Intervention / Treatment
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* Biological: V503
* Biological: Comparator: Menactra™ (Concomitant)
* Biological: Comparator: Adacel™ (Concomitant)
* Biological: Comparator: Menactra™ (Non-Concomitant)
* Biological: Comparator: Adacel™ (Non-concomitant)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concomitant Vaccination<br>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 | Biological: V503<br>* 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<br>Biological: Comparator: Menactra™ (Concomitant)<br>* Menactra™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm on Day 1.<br>Biological: Comparator: Adacel™ (Concomitant)<br>* Adacel™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm on Day 1.<br>|
| Experimental: Non-concomitant Vaccination<br>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 at Month 1 | Biological: V503<br>* 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<br>Biological: Comparator: Menactra™ (Non-Concomitant)<br>* Menactra™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm at Month 1.<br>Biological: Comparator: Adacel™ (Non-concomitant)<br>* Adacel™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm at Month 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 4 weeks following Month 6 vaccination | 
| 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. | Baseline and 4 weeks following Day 1 (Concomitant) or Month 1 (Non-concomitant) vaccination | 
| 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. | 4 weeks following Day 1 or Month 1 vaccination | 
| 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. | 4 weeks following Day 1 or Month 1 vaccination | 
| 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. | Day 1 through Day 5 following Day 1 vaccination | 
| 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. | Day 1 through Day 5 following Day 1 or Month 1 vaccination | 
| 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. | Up to 5 days following the Day 1 and Month 1 vaccination / visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Month 7 | 
| 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. | 4 weeks following Day 1 or Month 1 vaccination |