A Phase 3 Randomized, Double-Blinded, Controlled With GARDASIL® Efficacy, Immunogenicity and Safety Study of V503 [a 9-Valent HPV Vaccine] in Chinese Women 20 to 45 Years of Age
Overview
- Phase
- Phase 3
- Intervention
- V503
- Conditions
- Papillomavirus Infections
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 6000
- Locations
- 6
- Primary Endpoint
- Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 12-month Persistent Infection
- Status
- Active, not recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This study will evaluate the efficacy, immunogenicity and safety of 9-valent human papillomavirus (9vHPV; V503) vaccine in Chinese women 20 to 45 years of age. The primary hypotheses are: 9vHPV vaccine reduces the incidence of HPV 31-, 33-, 45-, 52-, and 58-related 12-month persistent infection at least 1 month post Dose 3, compared with quadrivalent HPV (qHPV) vaccine in women 20 to 45 years of age who are seronegative at Day 1 and polymerase chain reaction (PCR) negative Day 1 through Month 7 to the relevant HPV type; and 9vHPV vaccine induces non-inferior competitive luminex immunoassay (cLIA) geometric mean titers (GMTs) for each of HPV 6, 11, 16, and 18 one month post Dose 3, compared with qHPV vaccine in women 20 to 45 years of age who are seronegative at Day 1 and PCR negative Day 1 through Month 7 to the relevant HPV type.
Detailed Description
This study has two stages with the Stage I expected from Day 1 through Month 30, and the Stage II expected post-Month 30 to Month 90. The Stage I study is a case-driven study which aims to accrue at least 20 cases of HPV 31/33/45/52/58-related 12-month persistent infection and at least 39 cases of HPV 31/33/45/52/58-related 6-month persistent infection by completion of Month 30 visit. The Stage II study is a case-driven study which aims to accrue at least 12 cases of HPV 31/33/45/52/58-related cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3), cervical adenocarcinoma in situ (AIS), and cervical cancer observed in both Stage I and Stage II, by completion of Month 90 visit.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
V503
Single 0.5-mL intramuscular injection at Day 1, Month 2, and Month 6
Intervention: V503
Gardasil
Single 0.5-mL intramuscular injection at Day 1, Month 2, and Month 6
Intervention: Gardasil
Outcomes
Primary Outcomes
Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 12-month Persistent Infection
Time Frame: 1 month post vaccination 3 (Month 7) up to Month 30
A 12-month persistent infection This endpoint is defined to have occurred if a participant who is positive for the same HPV type by the HPV PCR assay in the LVPP/EEC swabs, biopsy, ECC or definitive therapy samples obtained in 3 or more consecutive visits over a period of at least 12 months. Incidence is defined as the number of cases of persistent infection per 10,000 person-years of follow-up in a treatment arm.
Stage I: Percentage of Participants Who Report at Least 1 Solicited Injection-site Adverse Event
Time Frame: up to 8 days post any vaccination
An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. AEs such as redness, swelling, and pain/tenderness/soreness at the injection site are recorded.
Stage I: Geometric Mean Titers to HPV Types 6, 11, 16, and 18 Antibodies
Time Frame: 1-month post vaccination 3 (Month 7)
Serum antibodies to HPV types 6/11/16/18 are measured with a Competitive Luminex Immunoassay (cLIA). Titers are reported in milli Merck Units/mL.
Stage I: Percentage of Participants Who Report at Least 1 Solicited Systemic Adverse Event
Time Frame: up to 30 days post any vaccination
An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. Systemic AEs are those not categorized as injection-site AEs.
Stage I: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE)
Time Frame: Day 1 up to approximately Month 30
An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. An SAE is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, or is another important medical event.
Stage II: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related CIN 2/3, AIS, and cervical cancer
Time Frame: Month 7 up to Month 90
This endpoint is defined to have occurred if on a single cervical biopsy, ECC, LEEP or Conization (cold knife/laser) specimen, there is: (a) a HPV Pathology Panel consensus diagnosis of CIN (grade 2 or 3), AIS, or cervical cancer; AND (b) detection of at least 1 of HPV types 31, 33, 45, 52 or 58 by Thinsection PCR in an adjacent section from the same tissue block. Disease incidence is defined as the number cases per 10,000 person-years of follow-up in a treatment arm.
Stages I/II: Percentage of Participants Who Experience at Least 1 Serious Adverse Event (SAE)
Time Frame: Day 1 up to approximately Month 90
An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with study vaccine. An AE can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study vaccine or a protocol-specified procedure, whether or not considered related to the study vaccine or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study vaccine or protocol-specified procedure is also an AE. An SAE is an AE that results in death, is life threatening, results in a persistent or significant disability or incapacity, results in or prolongs an existing hospitalization, is a congenital anomaly or birth defect, or is another important medical event.
Secondary Outcomes
- Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 6-month Persistent Cervical Infection(1 month post vaccination 3 (Month 7) up to Month 30)
- Stage II: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related genital warts, CIN 2/3, AIS, cervical cancer, VIN 2/3, VaIN 2/3, vulvar cancer, and vaginal cancer(Month 7 up to Month 90)
- Stage II: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related genital warts, CIN 1/2/3, AIS, cervical cancer, VIN 1/2/3, VaIN 1/2/3, vulvar cancer, and vaginal cancer(Month 7 to Month 90)
- Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 12-month Persistent Cervical Infection(1 month post vaccination 3 (Month 7) up to Month 30)
- Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 12-month Persistent Non-cervical Infection(1 month post vaccination 3 (Month 7) up to Month 30)
- Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 6-month Persistent Non-cervical Infection(1 month post vaccination 3 (Month 7) up to Month 30)
- Stage I: Percentage of Participants Who Seroconvert by cLIA to HPV Types 31, 33, 45, 52 , and 58(1 Month Post Vaccination 3 (Month 7))
- Stage II: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related CIN 1/2/3, AIS, and cervical cancer(Month 7 to Month 90)
- Stage II: Combined Incidence of HPV 31-, 33-, 45-, 52- , or 58-related Cervical, Vaginal and External Genital Biopsy and Definitive Therapy(Month 7 up to Month 90)
- Stage I: Combined Incidence of HPV 31-, 33-, 45-, 52-, and 58-related 6-month Persistent Infection(1 month post vaccination 3 (Month 7) up to Month 30)
- Stage I: Percentage of Participants Who Seroconvert by cLIA to HPV Types 6, 11, 16, and 18(1 Month Post Vaccination 3 (Month 7))
- Stage I: Combined Incidence of Papanicolaou (Pap) Test Abnormalities That are Related to HPV 31, 33, 45, 52, or 58(Month 7 up to Month 30)
- Stage I: Geometric Mean Titers of HPV 31, 33, 45, 52 , and 58 Antibodies(1 Month Post Vaccination 3 (Month 7))