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

Primary Purpose

Human Papillomavirus Infection

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
V503
Comparator: Menactra™ (Concomitant)
Comparator: Adacel™ (Concomitant)
Comparator: Menactra™ (Non-Concomitant)
Comparator: Adacel™ (Non-concomitant)
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Human Papillomavirus Infection

Eligibility Criteria

11 Years - 15 Years (Child)All SexesAccepts Healthy Volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Concomitant Vaccination

    Non-concomitant Vaccination

    Arm Description

    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

    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

    Outcomes

    Primary Outcome Measures

    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.
    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.
    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.
    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.
    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.
    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.
    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.

    Secondary Outcome Measures

    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.
    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.

    Full Information

    First Posted
    October 1, 2009
    Last Updated
    November 26, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00988884
    Brief Title
    A Study of V503 Given Concomitantly With Menactra™ and Adacel™ in 11 to 15 Year Olds (V503-005)
    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 Menactra™ and Adacel™ in Preadolescents and Adolescents (11 to 15 Year Olds)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    October 21, 2009 (Actual)
    Primary Completion Date
    February 22, 2011 (Actual)
    Study Completion Date
    February 22, 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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™.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Human Papillomavirus Infection

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    1241 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Concomitant Vaccination
    Arm Type
    Experimental
    Arm Description
    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
    Arm Title
    Non-concomitant Vaccination
    Arm Type
    Experimental
    Arm Description
    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
    Intervention Type
    Biological
    Intervention Name(s)
    V503
    Intervention Description
    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
    Intervention Type
    Biological
    Intervention Name(s)
    Comparator: Menactra™ (Concomitant)
    Intervention Description
    Menactra™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm on Day 1.
    Intervention Type
    Biological
    Intervention Name(s)
    Comparator: Adacel™ (Concomitant)
    Intervention Description
    Adacel™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm on Day 1.
    Intervention Type
    Biological
    Intervention Name(s)
    Comparator: Menactra™ (Non-Concomitant)
    Intervention Description
    Menactra™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm at Month 1.
    Intervention Type
    Biological
    Intervention Name(s)
    Comparator: Adacel™ (Non-concomitant)
    Intervention Description
    Adacel™ given as a single 0.5 mL intramuscular injection in the deltoid muscle of the dominant arm at Month 1.
    Primary Outcome Measure Information:
    Title
    Geometric Mean Titers (GMTs) of the Antibody Response to Each of the Human Papillomavirus (HPV) Types Contained in V503
    Description
    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
    Title
    Percentage of Participants With >=4-fold Increase in Antibody Titers to Neisseria Meningitidis Serogroups
    Description
    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
    Title
    Percentage of Participants Who Achieve Acceptable Titers of Anti-Diphtheria and Anti-Tetanus Antibody
    Description
    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
    Title
    Geometric Mean Titers of Pertussis Antibody Responses
    Description
    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
    Title
    Percentage of Participants With a V503 Injection-site Adverse Experience
    Description
    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
    Title
    Percentage of Participants With a Menactra™ or Adacel™ Injection-site Adverse Experience
    Description
    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
    Title
    Percentage of Participants With Maximum Temperature >=37.8 °C (>=100.0 °F) (Oral or Oral Equivalent)
    Description
    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 Outcome Measure Information:
    Title
    Percentage of Participants Who Seroconvert for Each of the HPV Types Contained in V503
    Description
    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
    Title
    Geometric Mean Titers of the Antibody Response to Neisseria Meningitidis Serogroups Contained in Menactra™
    Description
    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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    11 Years
    Maximum Age & Unit of Time
    15 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Monitor
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    26290207
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    26240207
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    27422279
    Citation
    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.
    Results Reference
    result
    Available IPD and Supporting Information:
    Available IPD/Information Type
    CSR Synopsis
    Available IPD/Information URL
    http://www.merck.com/clinical-trials/study.html?id=V503-005&kw=V503-005&tab=access

    Learn more about this trial

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

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