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)

Study Overview
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Brief Summary
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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.

Official Title
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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™

Conditions
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Cervical Cancers, Vulvar Cancers, Vaginal Cancers, Genital Warts

Intervention / Treatment
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* Biological: V503
* Biological: Placebo to V503


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 26 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 9vHPV Vaccine<br>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<br>* 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<br>|
| Placebo Comparator: Placebo<br>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<br>* 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<br>Biological: Placebo to V503<br>* Placebo to V503 (saline) given as a 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Base Study<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cervical cancer, Genital warts, Human papillomavirus vaccine, GARDASIL™