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

Merck Sharp & Dohme LLC1,241 enrolled

Overview

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™.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

1,241

Conditions

Human Papillomavirus Infection

Interventions

V503BIOLOGICAL

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

Comparator: Menactra™ (Concomitant)BIOLOGICAL

Menactra™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm on Day 1.

Comparator: Adacel™ (Concomitant)BIOLOGICAL

Adacel™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm on Day 1.

Eligibility

Sex: ALLMin age: 11 YearsMax age: 15 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

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

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

Geometric Mean Titers of Pertussis Antibody Responses

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Menactra™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm at Month 1.

Comparator: Adacel™ (Non-concomitant)BIOLOGICAL

Adacel™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm at Month 1.

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

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

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

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

Secondary Outcomes

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

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