Back to resultsA Study of V503, a 9-valent Human Papillomavirus (9vHPV) Vaccine in Females 12-26 Years of Age Who Have Previously Received GARDASIL™ (V503-006)
Primary Purpose
Cervical Cancers, Vulvar Cancers, Vaginal Cancers
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
V503
Placebo to V503
Sponsored by
About this trial
This is an interventional prevention trial for Cervical Cancers focused on measuring Cervical cancer, Genital warts, Human papillomavirus vaccine, GARDASIL™
Eligibility Criteria
Inclusion Criteria:
Participants Age 12 to 15 Years:
- Participant is in good health
- Parent/legal guardian and participant agree to provide study personnel with a primary telephone number for follow-up
- Participant received a 3-dose regimen of marketed GARDASIL™ within a 1 year period and the last dose of GARDASIL™ was at least 1 year from study day 1
- Participant has not received any other HPV vaccine
- Participant is not yet sexually active
Participants Age 16 to 26 Years:
- Participant is in good health
- Participant agrees to provide a primary telephone number for follow-up
- Participant received a 3-dose regimen of marketed GARDASIL™ within a 1 year period and the last dose of GARDASIL™ was at least 1 year from study day 1
- Participant has not received any other HPV vaccine
- Participant has never had Papanicolaou (Pap) testing or has only had normal results
- Participant has a history of 0 to 4 lifetime sexual partners at enrollment
Exclusion Criteria:
All participants:
- Participant has a history of severe allergic reaction that required medical intervention
- Participant has any disorder that would contraindicate intramuscular injections
- Participant is pregnant
- Participant is immunocompromised or has an autoimmune condition
- Participant has had a splenectomy
- Participant has received any immune globulin product or blood-derived product
- Participant has participated in a HPV vaccine clinical trial
Participants Age 16 to 26 Only:
- Participant expects to donate eggs during the study
- Participant has a history of abnormal cervical biopsy result
- Participant has a history of HPV-related external genital lesions, external genital cancer, HPV-related vaginal lesions, or vaginal cancer
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
9vHPV Vaccine
Placebo
Arm Description
Blinded 9vHPV vaccine (V503) 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Base Study. Participants will not continue to the Extension Study.
Blinded 0.5 mL intramuscular injection of saline placebo at Day 1, Month 2, and Month 6 of the Base Study. After completion of the Base Study, participants will be eligible to receive open-label 9vHPV 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Extension Study.
Outcomes
Primary Outcome Measures
Percentage of Participants Who Experience an Injection-site Adverse Event (AE) - Base Study
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. The percentage of participants who reported an AE that was associated with the injection site such as redness, swelling, and pain/tenderness/soreness was summarized.
Percentage of Participants With Body Temperature ≥100.0°F (≥37.8ºC) - Base Study
Participants collected their oral body temperature in the evening of their vaccination day and at the same time each day thereafter for 4 days. The maximum body temperature obtained within 5 days of any of the 3 vaccinations was recorded.
Percentage of Participants Who Experience a Systemic AE - Base Study
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. Systemic AEs were those not categorized as injection-site AEs.
Percentage of Participants Who Experience a Serious Adverse Event (SAE) Within 15 Days of Any Vaccination - Base Study
An SAE is one that results in death, disability/incapacity, or hospitalization or is life threatening, a congenital anomaly or birth defect, cancer, an overdose, or otherwise jeopardizes the participant and may require medical intervention.
Percentage of Participants Who Experience a Vaccine-related SAE Any Time During Study- Base Study
An SAE is one that results in death, disability/incapacity, or hospitalization or is life threatening, a congenital anomaly or birth defect, cancer, an overdose, or otherwise jeopardizes the participant and may require medical intervention. An SAE that is judged by the Investigator to be "definitely related," "probably related," or "possibly related" is defined as a vaccine-related SAE.
Percentage of Participants Who Experience a Severe Injection-site AE - Base Study
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. Participants were instructed to estimate the severity of AEs such as pain at injection site as mild (awareness of symptom, but easily tolerated), moderate (discomfort enough to cause interference with usual activities), or severe (incapacitating with inability to work or do usual activity). Additionally, participants were instructed to measure any swelling and/or erythema at its greatest width. Swelling or erythema with diameter >2 inches (>5 cm) was recorded as severe. All AEs associated with the injection site and reported as severe were summarized.
Secondary Outcome Measures
Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine - Base Study
Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using competitive luminex immunoassay (cLIA). The serostatus cutoffs (milli Merck U/mL) for HPV types were 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
NCT01047345
First Posted
January 11, 2010
Last Updated
October 30, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01047345
Brief Title
A Study of V503, a 9-valent Human Papillomavirus (9vHPV) Vaccine in Females 12-26 Years of Age Who Have Previously Received GARDASIL™ (V503-006)
Official Title
A Phase III, Randomized, International, Placebo-Controlled, Double-Blind Clinical Trial to Study the Tolerability and Immunogenicity of V503, a Multivalent Human Papillomavirus (HPV) L1 Virus-Like Particle (VLP) Vaccine, Given to Females 12-26 Years of Age Who Have Previously Received GARDASIL™
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
February 24, 2010 (Actual)
Primary Completion Date
June 10, 2011 (Actual)
Study Completion Date
November 28, 2015 (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 V503 (9vHPV vaccine), is well tolerated in girls and women between 12 and 26 years old who have previously been vaccinated with GARDASIL™. Participants will receive vaccination with 9vHPV vaccine or placebo on Day 1, Month 2, and Month 6 of the Base Study. Participants who receive placebo in the Base Study will be eligible to receive vaccination with 9vHPV vaccine on Day 1, Month 2, and Month 6 of the Extension Study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Cancers, Vulvar Cancers, Vaginal Cancers, Genital Warts
Keywords
Cervical cancer, Genital warts, Human papillomavirus vaccine, GARDASIL™
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
924 (Actual)
8. Arms, Groups, and Interventions
Arm Title
9vHPV Vaccine
Arm Type
Experimental
Arm Description
Blinded 9vHPV vaccine (V503) 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Base Study. Participants will not continue to the Extension Study.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Blinded 0.5 mL intramuscular injection of saline placebo at Day 1, Month 2, and Month 6 of the Base Study. After completion of the Base Study, participants will be eligible to receive open-label 9vHPV 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Extension Study.
Intervention Type
Biological
Intervention Name(s)
V503
Intervention Description
V503 (9vHPV) vaccine given as a 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Base Study or the Study Extension
Intervention Type
Biological
Intervention Name(s)
Placebo to V503
Intervention Description
Placebo to V503 (saline) given as a 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Base Study
Primary Outcome Measure Information:
Title
Percentage of Participants Who Experience an Injection-site Adverse Event (AE) - Base Study
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. The percentage of participants who reported an AE that was associated with the injection site such as redness, swelling, and pain/tenderness/soreness was summarized.
Time Frame
up to 5 days after any vaccination - Base Study
Title
Percentage of Participants With Body Temperature ≥100.0°F (≥37.8ºC) - Base Study
Description
Participants collected their oral body temperature in the evening of their vaccination day and at the same time each day thereafter for 4 days. The maximum body temperature obtained within 5 days of any of the 3 vaccinations was recorded.
Time Frame
up to 5 days after any vaccination - Base Study
Title
Percentage of Participants Who Experience a Systemic AE - Base Study
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. Systemic AEs were those not categorized as injection-site AEs.
Time Frame
up to 14 days after any vaccination - Base Study
Title
Percentage of Participants Who Experience a Serious Adverse Event (SAE) Within 15 Days of Any Vaccination - Base Study
Description
An SAE is one that results in death, disability/incapacity, or hospitalization or is life threatening, a congenital anomaly or birth defect, cancer, an overdose, or otherwise jeopardizes the participant and may require medical intervention.
Time Frame
up to 14 days after any vaccination - Base Study
Title
Percentage of Participants Who Experience a Vaccine-related SAE Any Time During Study- Base Study
Description
An SAE is one that results in death, disability/incapacity, or hospitalization or is life threatening, a congenital anomaly or birth defect, cancer, an overdose, or otherwise jeopardizes the participant and may require medical intervention. An SAE that is judged by the Investigator to be "definitely related," "probably related," or "possibly related" is defined as a vaccine-related SAE.
Time Frame
Up to 7 months - Base Study
Title
Percentage of Participants Who Experience a Severe Injection-site AE - Base Study
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. Participants were instructed to estimate the severity of AEs such as pain at injection site as mild (awareness of symptom, but easily tolerated), moderate (discomfort enough to cause interference with usual activities), or severe (incapacitating with inability to work or do usual activity). Additionally, participants were instructed to measure any swelling and/or erythema at its greatest width. Swelling or erythema with diameter >2 inches (>5 cm) was recorded as severe. All AEs associated with the injection site and reported as severe were summarized.
Time Frame
up to 5 days after any vaccination - Base Study
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine - Base Study
Description
Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using competitive luminex immunoassay (cLIA). The serostatus cutoffs (milli Merck U/mL) for HPV types were 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
4 weeks post-vaccination 3 (Month 7; End of Base Study)
Other Pre-specified Outcome Measures:
Title
Percentage of Participants Who Experience an SAE- Extension Study
Description
An SAE is one that results in death, disability/incapacity, or hospitalization or is life threatening, a congenital anomaly or birth defect, cancer, an overdose, or otherwise jeopardizes the participant and may require medical intervention.
Time Frame
up to Month 7 - Extension Study
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
26 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Participants Age 12 to 15 Years:
Participant is in good health
Parent/legal guardian and participant agree to provide study personnel with a primary telephone number for follow-up
Participant received a 3-dose regimen of marketed GARDASIL™ within a 1 year period and the last dose of GARDASIL™ was at least 1 year from study day 1
Participant has not received any other HPV vaccine
Participant is not yet sexually active
Participants Age 16 to 26 Years:
Participant is in good health
Participant agrees to provide a primary telephone number for follow-up
Participant received a 3-dose regimen of marketed GARDASIL™ within a 1 year period and the last dose of GARDASIL™ was at least 1 year from study day 1
Participant has not received any other HPV vaccine
Participant has never had Papanicolaou (Pap) testing or has only had normal results
Participant has a history of 0 to 4 lifetime sexual partners at enrollment
Exclusion Criteria:
All participants:
Participant has a history of severe allergic reaction that required medical intervention
Participant has any disorder that would contraindicate intramuscular injections
Participant is pregnant
Participant is immunocompromised or has an autoimmune condition
Participant has had a splenectomy
Participant has received any immune globulin product or blood-derived product
Participant has participated in a HPV vaccine clinical trial
Participants Age 16 to 26 Only:
Participant expects to donate eggs during the study
Participant has a history of abnormal cervical biopsy result
Participant has a history of HPV-related external genital lesions, external genital cancer, HPV-related vaginal lesions, or vaginal cancer
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
26411885
Citation
Garland SM, Cheung TH, McNeill S, Petersen LK, Romaguera J, Vazquez-Narvaez J, Bautista O, Shields C, Vuocolo S, Luxembourg A. Safety and immunogenicity of a 9-valent HPV vaccine in females 12-26 years of age who previously received the quadrivalent HPV vaccine. Vaccine. 2015 Nov 27;33(48):6855-64. doi: 10.1016/j.vaccine.2015.08.059. Epub 2015 Sep 26.
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
PubMed Identifier
29211620
Citation
Moreira ED, Giuliano AR, de Hoon J, Iversen OE, Joura EA, Restrepo J, Van Damme P, Vandermeulen C, Ellison MC, Krick A, Shields C, Heiles B, Luxembourg A. Safety profile of the 9-valent human papillomavirus vaccine: assessment in prior quadrivalent HPV vaccine recipients and in men 16 to 26 years of age. Hum Vaccin Immunother. 2018 Feb 1;14(2):396-403. doi: 10.1080/21645515.2017.1403700. Epub 2017 Dec 14.
Results Reference
derived
Available IPD and Supporting Information:
Available IPD/Information Type
CSR Synopsis
Available IPD/Information URL
http://www.merck.com/clinical-trials/study.html?id=V503-006&kw=V503-006&tab=access
Learn more about this trial
A Study of V503, a 9-valent Human Papillomavirus (9vHPV) Vaccine in Females 12-26 Years of Age Who Have Previously Received GARDASIL™ (V503-006)
We'll reach out to this number within 24 hrs