A Study of V503 Vaccine Given Concomitantly With REPEVAX™ in 11 to 15 Year Olds (V503-007)
Primary Purpose
Papillomavirus Infections
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
V503 Vaccine
REPEVAX™ (Concomitant)
REPEVAX™ (Non-concomitant)
Sponsored by
About this trial
This is an interventional prevention trial for Papillomavirus Infections
Eligibility Criteria
Inclusion criteria:
- Participant is in good health
- Participant's parent/legal guardian can read, understand, and complete the vaccination report card
- Participant is not sexually active and does not plan on becoming sexually active during the study
- Participant has received a documented full primary immunization series against diphtheria, tetanus, pertussis, and poliovirus (inactivated and/or oral poliovirus), but not in the last 5 years. There must be a 5-year interval from a prior vaccination containing any one of these vaccine antigens.
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
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 Repevax™ 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 Repevax™ 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 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 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 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 Repevax™ Injection-site Adverse Experience
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 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.
Percentage of Participants With a Systemic Adverse Experience
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
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
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 Who Achieve Acceptable Titers of Anti-Poliovirus 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 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
Percentage of Participants Who Seroconvert for Each of the HPV Types
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.
Full Information
NCT ID
NCT01073293
First Posted
February 19, 2010
Last Updated
October 30, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01073293
Brief Title
A Study of V503 Vaccine Given Concomitantly With REPEVAX™ in 11 to 15 Year Olds (V503-007)
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 REPEVAX™ in Preadolescents and Adolescents (11 to 15 Year Olds)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
April 22, 2010 (Actual)
Primary Completion Date
June 16, 2011 (Actual)
Study Completion Date
June 16, 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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Papillomavirus Infections
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1054 (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 Repevax™ 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 Repevax™ 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 Vaccine
Intervention Description
V503 (Multivalent HPV L1 VLP vaccine) given as a 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6
Intervention Type
Biological
Intervention Name(s)
REPEVAX™ (Concomitant)
Intervention Description
REPEVAX™ given as a single 0.5 mL intramuscular injection at Day 1
Intervention Type
Biological
Intervention Name(s)
REPEVAX™ (Non-concomitant)
Intervention Description
REPEVAX™ given as a single 0.5 mL intramuscular injection 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 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.
Time Frame
4 weeks following Month 6 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 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 Repevax™ Injection-site Adverse Experience
Description
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.
Time Frame
Day 1 through Day 5 following Day 1 (Concomitant) or Month 1 (Non-concomitant) 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
Title
Percentage of Participants With a Systemic Adverse Experience
Description
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.
Time Frame
Up to 15 days following the Day 1 and Month 1 vaccination / visit
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. 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.
Time Frame
4 weeks following Day 1 (Concomitant) or Month 1 (Non-concomitant) 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. Titers are expressed as enzyme-linked immunoassay units/mL (ELU/mL).
Time Frame
4 weeks following Day 1 (Concomitant) or Month 1 (Non-concomitant) vaccination
Title
Percentage of Participants Who Achieve Acceptable Titers of Anti-Poliovirus 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 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.
Time Frame
4 weeks following Day 1 (Concomitant) or Month 1 (Non-concomitant) vaccination
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Seroconvert for Each of the HPV Types
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
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:
Participant is in good health
Participant's parent/legal guardian can read, understand, and complete the vaccination report card
Participant is not sexually active and does not plan on becoming sexually active during the study
Participant has received a documented full primary immunization series against diphtheria, tetanus, pertussis, and poliovirus (inactivated and/or oral poliovirus), but not in the last 5 years. There must be a 5-year interval from a prior vaccination containing any one of these vaccine antigens.
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
25831420
Citation
Kosalaraksa P, Mehlsen J, Vesikari T, Forsten A, Helm K, Van Damme P, Joura EA, Ciprero K, Maansson R, Luxembourg A, Sobanjo-ter Meulen A. An open-label, randomized study of a 9-valent human papillomavirus vaccine given concomitantly with diphtheria, tetanus, pertussis and poliomyelitis vaccines to healthy adolescents 11-15 years of age. Pediatr Infect Dis J. 2015 Jun;34(6):627-34. doi: 10.1097/INF.0000000000000694.
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=V503-007&kw=V503-007&tab=access
Learn more about this trial
A Study of V503 Vaccine Given Concomitantly With REPEVAX™ in 11 to 15 Year Olds (V503-007)
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