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

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)

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 Overview

• Status: Completed
• Conditions: Human Papillomavirus Infection
• Intervention / Treatment: Biological: V503; Biological: Comparator: Menactra™ (Concomitant); Biological: Comparator: Adacel™ (Concomitant); Biological: Comparator: Menactra™ (Non-Concomitant); Biological: Comparator: Adacel™ (Non-concomitant)

• Study Type: Interventional
• Enrollment (Actual): 1241
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years to 15 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Moreira ED Jr, Block SL, Ferris D, Giuliano AR, Iversen OE, Joura EA, Kosalaraksa P, Schilling A, Van Damme P, Bornstein J, Bosch FX, Pils S, Cuzick J, Garland SM, Huh W, Kjaer SK, Qi H, Hyatt D, Martin J, Moeller E, Ritter M, Baudin M, Luxembourg A. Safety Profile of the 9-Valent HPV Vaccine: A Combined Analysis of 7 Phase III Clinical Trials. Pediatrics. 2016 Aug;138(2):e20154387. doi: 10.1542/peds.2015-4387. Epub 2016 Jul 15.
• Rodrigues S, Grenha A. Activation of Macrophages: Establishing a Role for Polysaccharides in Drug Delivery Strategies Envisaging Antibacterial Therapy. Curr Pharm Des. 2015;21(33):4869-87. doi: 10.2174/1381612821666150820103910.
• Schilling A, Parra MM, Gutierrez M, Restrepo J, Ucros S, Herrera T, Engel E, Huicho L, Shew M, Maansson R, Caldwell N, Luxembourg A, Ter Meulen AS. Coadministration of a 9-Valent Human Papillomavirus Vaccine With Meningococcal and Tdap Vaccines. Pediatrics. 2015 Sep;136(3):e563-72. doi: 10.1542/peds.2014-4199. Epub 2015 Aug 3.

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2009
• Primary Completion (Actual): February 22, 2011
• Study Completion (Actual): February 22, 2011

Study Registration Dates

• First Submitted: October 1, 2009
• First Submitted That Met QC Criteria: October 1, 2009
• First Posted (Estimate): October 2, 2009

Study Record Updates

• Last Update Posted (Actual): December 14, 2018
• Last Update Submitted That Met QC Criteria: November 26, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Tumor Virus Infections; Papillomavirus Infections
• Other Study ID Numbers: V503-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis