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)

Phase 3

Completed

Conditions: Vulvar Cancers
Vaginal Cancers
Genital Warts
Cervical Cancers

Interventions: Biological: V503
Biological: Placebo to V503

Registration Number: NCT01047345

Lead Sponsor: Merck Sharp & Dohme LLC

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 available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 924

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo to V503	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.
9vHPV Vaccine	V503	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.
Placebo	V503	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Experience an Injection-site Adverse Event (AE) - Base Study	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	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	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	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	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	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine - Base Study	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.