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)

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™

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.

Study Overview

• Status: Completed
• Conditions: Genital Warts; Cervical Cancers; Vulvar Cancers; Vaginal Cancers
• Intervention / Treatment: Biological: V503; Biological: Placebo to V503

• Study Type: Interventional
• Enrollment (Actual): 924
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 26 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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
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.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 5 days after any vaccination - Base Study
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.	up to 5 days after any vaccination - Base Study
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.	up to 14 days after any vaccination - Base Study
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.	up to 14 days after any vaccination - Base Study
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.	Up to 7 months - Base Study
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.	up to 5 days after any vaccination - Base Study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 weeks post-vaccination 3 (Month 7; End of Base Study)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experience an SAE- 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.	up to Month 7 - Extension Study

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2010
• Primary Completion (Actual): June 10, 2011
• Study Completion (Actual): November 28, 2015

Study Registration Dates

• First Submitted: January 11, 2010
• First Submitted That Met QC Criteria: January 11, 2010
• First Posted (Estimate): January 12, 2010

Study Record Updates

• Last Update Posted (Actual): November 27, 2018
• Last Update Submitted That Met QC Criteria: October 30, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Cervical cancer; Genital warts; Human papillomavirus vaccine; GARDASIL™
• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; DNA Virus Infections; Skin Diseases, Infectious; Warts; Papillomavirus Infections; Skin Diseases, Viral; Tumor Virus Infections; Vaginal Diseases; Vulvar Diseases; Uterine Cervical Neoplasms; Vulvar Neoplasms; Vaginal Neoplasms; Condylomata Acuminata
• Other Study ID Numbers: V503-006; 2010_504 (Other Identifier: Merck Registration Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis