The purpose of this study was to evaluate the safety, efficacy, and immunogenicity of V503 in comparison to GARDASIL. The primary hypotheses tested in the study were 1) V503 administered to 16- to 26-year-old adolescents and young women is generally well-tolerated, 2) V503 reduces combined incidence of Human Papillomavirus (HPV) Type 31/33/45/52/58-related disease compared with GARDASIL, and 3) V503 induces non-inferior geometric mean titers for HPV Type 6/11/16/18 antibodies compared with GARDASIL.
The study included a dose-finding evaluation of a 3-dose regimen of V503 and GARDASIL, a safety/efficacy evaluation of a 3-dose regimen of the selected V503 dose formulation and GARDASIL, and an extension consisting of 2 substudies: an evaluation of immune memory in participants receiving a fourth vaccination with V503 (Cohort 1), and an opportunity for participants who received GARDASIL in the Base Study to receive a 3-dose regimen of V503 (Cohort 2).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
14,840
GARDASIL (quadrivalent HPV \[Types 6, 11, 16, and 18\] L1 virus-like particle vaccine), 0.5 mL injection in 3 dose regimen
V503 (9-valent HPV \[Types 6, 11, 16, 18, 31, 33, 45, 52, and 58\] L1 virus-like particle vaccine), 0.5 mL injection in 3 dose regimen (and a fourth injection for Cohort 1 only).
Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Disease (Test of Hypothesis)
HPV Type 31/33/45/52/58-related high-grade Cervical Intraepithelial Neoplasia (CIN 2/3), Adenocarcinoma in Situ (AIS), Invasive Cervical Carcinoma, high-grade Vulvar Intraepithelial Neoplasia (VIN 2/3), high-grade Vaginal Intraepithelial Neoplasia (VaIN 2/3), vulvar cancer, or vaginal cancer were determined by clinical/pathologic criteria and positive Polymerase Chain Reaction (PCR) assay for virus subtype. This outcome measure reports data based on the protocol-specified plan of conducting hypothesis testing when at least 30 cases had accumulated. The cutoff date for this analysis was 10 April 2013. Disease incidence was defined as the number of primary efficacy cases per 10,000 person-years of follow-up in a treatment arm.
Time frame: From Day 1 until >=30 cases accumulate, up to Month 54 in the base study
Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Disease (End-of-study Update)
HPV Type 31/33/45/52/58-related high-grade Cervical Intraepithelial Neoplasia (CIN 2/3), Adenocarcinoma in Situ (AIS), Invasive Cervical Carcinoma, high-grade Vulvar Intraepithelial Neoplasia (VIN 2/3), high-grade Vaginal Intraepithelial Neoplasia (VaIN 2/3), vulvar cancer, or vaginal cancer were determined by clinical/pathologic criteria and positive Polymerase Chain Reaction (PCR) assay for virus subtype. This outcome measure reports cumulative study data through 10 March 2014. Disease incidence was defined as the number of primary efficacy cases per 10,000 person-years of follow-up in a treatment arm.
Time frame: Up to Month 54 in the base study
Base Study: Geometric Mean Titers (GMTs) to HPV Types 6/11/16/18/31/33/45/52/58
Serum antibodies to HPV types 6/11/16/18/31/33/45/52/58 were measured with a Competitive Luminex Immunoassay. Titers are reported in milli Merck Units/mL. Statistical analysis was performed only for HPV types contained in both vaccines.
Time frame: 4 weeks postdose 3 in the base study
Base Study: Percentage of Participants With One or More Adverse Event
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 product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE.
Time frame: Up to Month 7 (low- and high-dose V503) or up to Month 54 (mid-dose V503 and Gardasil)
Base Study: Percentage of Participants With One or More Injection-site Adverse Event
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 product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. AEs such as redness, swelling, and pain/tenderness/soreness at the injection site were recorded.
Time frame: Up to Day 5 after any vaccination
Base Study: Percentage of Participants With One or More Non-injection-site (Systemic) Adverse Event
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 product. 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 Day 15 after any vaccination
Base Study: Percentage of Participants With One or More Vaccine-related Adverse Event
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 product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. An AE that is judged by the investigator to be "definitely related," "probably related," or "possibly related" to the study drug is defined as a vaccine-related AE.
Time frame: Up to Month 7 (low- and high-dose V503) or up to Month 54 (mid-dose V503 and Gardasil)
Base Study: Percentage of Participants With Study Medication Withdrawn Due to an Adverse Event
An adverse event 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 product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse event.
Time frame: Up to Month 6
Base Study: Combined Incidence of HPV Type 31/33/45/52/58-related Persistent Infection
Combined Incidence of HPV Type 31/33/45/52/58-related persistent infection as determined by clinical/pathologic criteria and positive Polymerase Chain Reaction (PCR) assay for virus subtype. Persistent infection was defined as infection detected in samples from \>=2 consecutive visits 6 months (+/-1 month visit window) or longer apart. Incidence was defined as the number of cases of persistent infection per 10,000 person-years of follow-up in a treatment arm.
Time frame: Up to Month 54 in the base study
Base Study: Percentage of Participants Who Are Seropositive for HPV Types 6/11/16/18/31/33/45/52/58
Serum antibodies to HPV types were measured with a Competitive Luminex Immunoassay. 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 Types 33, 45, 52, and 58: ≥8.
Time frame: 4 weeks postdose 3
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