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)

• ClinicalTrials.gov Identifier: NCT01047345
• Recruitment Status: Completed
• First Posted: January 12, 2010
• Results First Posted: December 22, 2014
• Last Update Posted: November 27, 2018
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Tracking Information

• First Submitted Date: January 11, 2010
• First Posted Date: January 12, 2010
• Results First Submitted Date: December 12, 2014
• Results First Posted Date: December 22, 2014
• Last Update Posted Date: November 27, 2018
• Actual Study Start Date: February 24, 2010
• Actual Primary Completion Date: June 10, 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 31, 2016)

• Percentage of Participants Who Experience an Injection-site Adverse Event (AE) - Base Study [ Time Frame: up to 5 days after any vaccination - 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 [ Time Frame: up to 5 days after any vaccination - 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 [ Time Frame: up to 14 days after any vaccination - 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 [ Time Frame: up to 14 days after 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 [ Time Frame: Up to 7 months - 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 [ Time Frame: up to 5 days after any vaccination - 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.

• Original Primary Outcome Measures (submitted: January 11, 2010): Number of participants who experience serious or non-serious adverse events [ Time Frame: Day 1 to Month 7 ]

Current Secondary Outcome Measures (submitted: December 12, 2014)

Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine - Base Study [ Time Frame: 4 weeks post-vaccination 3 (Month 7; End of 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.

• Original Secondary Outcome Measures (submitted: January 11, 2010): Number of participants who are seropositive to each of the HPV types contained in V503 [ Time Frame: Month 7 ]

Current Other Pre-specified Outcome Measures (submitted: October 31, 2016)

Percentage of Participants Who Experience an SAE- Extension Study [ Time Frame: up to Month 7 - Extension 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.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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™
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention

Condition

• Cervical Cancers
• Vulvar Cancers
• Vaginal Cancers
• Genital Warts

Intervention

• Biological: V503
  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
• Biological: Placebo to V503
  Placebo to V503 (saline) given as a 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Base Study

Study Arms

• Experimental: 9vHPV Vaccine
  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.
  Intervention: Biological: V503
• Placebo Comparator: Placebo
  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.
  Interventions:

  • Biological: V503
  • Biological: Placebo to V503

Publications *

• 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.
• 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). pii: e20154387. doi: 10.1542/peds.2015-4387. Epub 2016 Jul 15.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 30, 2012): 924
• Original Estimated Enrollment (submitted: January 11, 2010): 900
• Actual Study Completion Date: November 28, 2015
• Actual Primary Completion Date: June 10, 2011 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 12 Years to 26 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: Canada, Colombia, Denmark, Hong Kong, Mexico, Puerto Rico, Sweden, United States

Administrative Information

• NCT Number: NCT01047345
• Other Study ID Numbers: V503-006; 2010_504 ( Other Identifier: Merck Registration Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Responsible Party: Merck Sharp & Dohme Corp.
• Study Sponsor: Merck Sharp & Dohme Corp.
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

• PRS Account: Merck Sharp & Dohme Corp.
• Verification Date: October 2018