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
About this trial
This is an interventional prevention trial for Human Papillomavirus Infection
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
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
NCT ID
NCT00988884
First Posted
October 1, 2009
Last Updated
November 26, 2018
Sponsor
Merck Sharp & Dohme LLC
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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