A Study of V503 Vaccine Given Concomitantly With REPEVAX™ in 11 to 15 Year Olds (V503-007)

Study Overview
=================
Brief Summary
-----------------
This study will evaluate whether co-administration of the first dose of V503 and REPEVAX™ is well tolerated and causes a non-inferior immune response when compared to administration of REPEVAX™ one month following the first dose of V503.

Official Title
-----------------
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 REPEVAX™ in Preadolescents and Adolescents (11 to 15 Year Olds)

Conditions
-----------------
Papillomavirus Infections

Intervention / Treatment
-----------------
* Biological: V503 Vaccine
* Biological: REPEVAX™ (Concomitant)
* Biological: REPEVAX™ (Non-concomitant)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Participant is in good health Participant's parent/legal guardian can read, understand, and complete the vaccination report card Participant is not sexually active and does not plan on becoming sexually active during the study Participant has received a documented full primary immunization series against diphtheria, tetanus, pertussis, and poliovirus (inactivated and/or oral poliovirus), but not in the last 5 years. There must be a 5-year interval from a prior vaccination containing any one of these vaccine antigens. Exclusion Criteria: Participant has a known allergy to any vaccine component of V503 or REPEVAX™ Participant has had a severe reaction affecting the brain (e.g., evolving encephalopathy) within 7 days after a previous dose of a pertussis-containing vaccine Participant has had a progressive severe illness affecting the brain after a previous dose of tetanus, diphtheria, poliovirus or a component pertussis combination (acellular and whole cell) vaccine Participant ever had Guillain-Barré syndrome or brachial neuritis following a previous dose of a tetanus-containing vaccine Participant has a condition that is a contraindication to vaccination as indicated in the most up to date package inserts of REPEVAX™ Participant has a history of severe allergic reaction that required medical intervention Participant has hemophilia, thrombocytopenia, is receiving anticoagulation therapy and/or has any coagulation disorder that would contraindicate intramuscular injections Participant is concurrently enrolled in clinical studies of investigational agents Female participant is pregnant Participant has donated blood within 1 week prior to first study vaccination, or intends to donate during the study Participant is immunocompromised, immunodeficient, or has an autoimmune condition Participant has had a splenectomy Participant has received immunosuppressive therapies in the prior year Participant has received immune globulin product or blood-derived product in the last 3 months Participant has received inactivated vaccine(s) within 14 days or live vaccine(s) within 21 days of first study vaccination Participant has received a marketed HPV vaccine or has participated in an HPV vaccine trial Participant has received a tetanus, diphtheria, pertussis, or poliovirus (inactivated and/or oral poliovirus) vaccination within the last 5 years Participant has a fever ≥100°F within 24 hours of vaccination Participant has any history or current condition, therapy, lab abnormality, or other circumstance such that it is not in the best interest of the participant to participate Participant and parent/legal guardian are unable to give assent/consent Participant is unlikely to adhere to the study procedures or is planning to relocate during the study Participant has recent history of illicit drug or alcohol abuse Participant has a history of HPV

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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 Repevax™ given as a 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm on Day 1 | Biological: V503 Vaccine<br>* V503 (Multivalent HPV L1 VLP vaccine) given as a 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6<br>Biological: REPEVAX™ (Concomitant)<br>* REPEVAX™ given as a single 0.5 mL intramuscular injection at 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 Repevax™ given as a 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm at Month 1 | Biological: V503 Vaccine<br>* V503 (Multivalent HPV L1 VLP vaccine) given as a 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6<br>Biological: REPEVAX™ (Non-concomitant)<br>* REPEVAX™ given as a single 0.5 mL intramuscular injection at Month 1<br>|

What is the study measuring?
-----------------
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 for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 were measured using a competitive Luminex immunoassay. Titers are reported in milli Merck Units/mL. | 4 weeks following Month 6 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 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 Repevax™ Injection-site Adverse Experience | 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. 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 vaccine is also an AE. Only injection-site AEs in the arm that received Repevax™ vaccination were reported for this endpoint. | Day 1 through Day 5 following Day 1 (Concomitant) or Month 1 (Non-concomitant) 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 | 
| Percentage of Participants With a Systemic Adverse Experience | For the Concomitant Vaccination group, systemic AEs were collected after the Day 1 vaccination and the Month 1 visit; for the Non-concomitant Vaccination group, systemic AEs were collected after the Day 1 vaccination and the Month 1 vaccination. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body that is 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 vaccine is also an adverse experience. A systemic AE was an AE that was not associated with the injection site. | Up to 15 days following the Day 1 and Month 1 vaccination / visit | 
| 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. Serum titers of neutralizing antibody to tetanus toxin were measured using an enzyme immunoassay. The lower limits of quantitation of the assays was 0.01 International Units (IU)/mL and 0.04 IU/mL, respectively. Acceptable titers refer to the World Health Organization-defined protective titer of >=0.1 IU/mL. | 4 weeks following Day 1 (Concomitant) or Month 1 (Non-concomitant) 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. Titers are expressed as enzyme-linked immunoassay units/mL (ELU/mL). | 4 weeks following Day 1 (Concomitant) or Month 1 (Non-concomitant) vaccination | 
| Percentage of Participants Who Achieve Acceptable Titers of Anti-Poliovirus 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 poliovirus type 1, 2, and 3 were measured using a microneutralization assay. Serial dilutions of sera were incubated with type-specific standard poliovirus and sensitive cells. Neutralization of the virus was measured by cell staining. Acceptable titers were defined as neutralization at >=1:8 dilution of serum. | 4 weeks following Day 1 (Concomitant) or Month 1 (Non-concomitant) vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Seroconvert for Each of the HPV Types | 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 |