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

Phase 3

Completed

Conditions: Papillomavirus Infections

Interventions: Biological: V503 Vaccine
Biological: REPEVAX™ (Non-concomitant)
Biological: REPEVAX™ (Concomitant)

Registration Number: NCT01073293

Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1054

Inclusion Criteria

Not provided

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Concomitant Vaccination	V503 Vaccine	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
Non-concomitant Vaccination	REPEVAX™ (Non-concomitant)	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
Concomitant Vaccination	REPEVAX™ (Concomitant)	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
Non-concomitant Vaccination	V503 Vaccine	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

Primary Outcome Measures

Name	Time	Method
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 Systemic Adverse Experience	Up to 15 days following the Day 1 and Month 1 vaccination / visit	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.
Percentage of Participants Who Achieve Acceptable Titers of Anti-Diphtheria and Anti-Tetanus Antibody	4 weeks following Day 1 (Concomitant) or Month 1 (Non-concomitant) 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. 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.
Geometric Mean Titers of Pertussis Antibody Responses	4 weeks following Day 1 (Concomitant) or Month 1 (Non-concomitant) 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. Titers are expressed as enzyme-linked immunoassay units/mL (ELU/mL).
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 vaccine is also an AE. Only injection-site AEs in the arm that received V503 vaccination were reported for this endpoint.
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 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.
Percentage of Participants With a Repevax™ Injection-site Adverse Experience	Day 1 through Day 5 following Day 1 (Concomitant) or Month 1 (Non-concomitant) vaccination	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.
Percentage of Participants Who Achieve Acceptable Titers of Anti-Poliovirus Antibody	4 weeks following Day 1 (Concomitant) or Month 1 (Non-concomitant) 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 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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Seroconvert for Each of the HPV Types	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.