A Phase III Clinical Trial to Study the Immunogenicity, Tolerability, and Manufacturing Consistency of V503 (A Multivalent Human Papillomavirus [HPV] L1 Virus-Like Particle [VLP] Vaccine) in Preadolescents and Adolescents (9 to 15 Year Olds) With a Comparison to Young Women (16 to 26 Year Olds)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 3,074
- 主要终点
- Extension Study: Percentage of Participants Who Are Seropositive to Each of the HPV Types Contained in the Vaccine
研究概览
简要总结
This study will evaluate the immunogenicity and tolerability of V503 (a multivalent human papillomavirus [HPV] L1 virus-like particle [VLP] vaccine) in preadolescent and adolescent participants between 9 and 15 years old and demonstrate the consistency of the manufactured vaccine through assessment of 3 different final manufacturing process lots of V503.
The primary hypotheses are as follows:
- The 9-valent HPV L1 VLP vaccine when administered to preadolescent and adolescent boys and girls 9 to 15 years of age and young women 16 to 26 years of age is generally well-tolerated.
- 9-valent HPV L1 VLP vaccine induces non-inferior immune responses in preadolescent and adolescent girls 9 to 15 years of age who are seronegative at Day 1 to the relevant HPV type compared to young women 16 to 26 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, as measured by anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 geometric mean titers (GMTs) at 4 weeks post-dose 3.
- The 9-valent HPV L1 VLP vaccine induces non-inferior immune responses in preadolescent and adolescent boys 9 to 15 years of age who are seronegative at Day 1 to the relevant HPV type compared to young women 16 to 26 years of age who are seronegative at Day 1 and PCR-negative Day 1 through Month 7 to the relevant HPV type, as measured by anti-HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 GMTs at 4 weeks post-dose 3.
- Three separate final manufacturing process (FMP) lots of the 9-valent HPV L1 VLP vaccine induce similar immune responses, as measured by anti-HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 GMTs at 4 weeks post-dose 3.
详细描述
The base study V503-002 was a 12-month study that collected immunogenicity data through Month 7 and safety data through Month 12.
An optional extension study (V503-002 EXT1) collected safety and immunogenicity information through Month 36. Participants enrolled in the 16- to 26-year-old cohort in the base study were not included in EXT1. Per protocol, EXT1 included immunogenicity data from a subset of 9- to 15-year-old females and safety data from all 9- to 15-year-old females regardless of lot administered.
An optional second extension study (V503-002 EXT2) collected long-term safety and immunogenicity information through approximately Month 126. No study vaccine was administered in the extension studies. Participants enrolled in the 16- to 26-year-old cohort in the base study were not included in EXT2. Per protocol, EXT2 included immunogenicity data from a subset of 9- to 15-year-old females and effectiveness and safety data from all 9- to 15-year-old females regardless of lot administered.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 9 Years 至 26 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Boys and Girls Age 9 to 15:
- •Participant has not had sexual intercourse prior to the study and does not plan to become sexually active during the study period Day 1 to Month 7
- •Women Age 16 to 26:
- •Participant has never had Pap testing or has had only normal results
- •Participant has had 0 to 4 sexual partners at the time of enrollment
排除标准
- •Boys and Girls Age 9 to 15:
- •History of allergic reaction that required medical intervention
- •Currently enrolled in any other clinical study
- •Participant is pregnant
- •Participant is immunocompromised or has taken immunosuppressants in the last year
- •Participant has received a marketed HPV vaccine or participated in an HPV vaccine clinical trial
- •Participant has a history of positive test for HPV
- •Women Age 16 to 26:
- •History of allergic reaction that required medical intervention
- •Currently enrolled in any other clinical study
- •Participant is pregnant
- •Participant is immunocompromised or has taken immunosuppressants in the last year
- •Participant has received a marketed HPV vaccine or participated in an HPV vaccine clinical trial
- •Participant has a history of positive test for HPV
- •Participant has a history of abnormal cervical biopsy result
- •Participant has a history of external genital lesions
结局指标
主要结局
Extension Study: Percentage of Participants Who Are Seropositive to Each of the HPV Types Contained in the Vaccine
时间窗: Up to ~Month 126
Serum antibody titers for HPV VLPs Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 was determined and reported in milli Merck Units/mL. The percentage of participants seropositive to each HPV type was reported. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered.
Base Study: Geometric Mean Titers (GMTs) for Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Females [Lot 1] and 16- to 26-Year-Old Females [Lot 1])
时间窗: 4 weeks post-vaccination 3 (Month 7)
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 a competitive luminex immunoassay (cLIA). Titers were reported in milli Merck Units/mL.
Base Study: Percentage of Participants With Systemic AEs
时间窗: Up to 15 days after any vaccination
An AE was 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 was also an AE. Systemic AEs were those not categorized as injection-site AEs.
Extension Study: GMTs For Each of the HPV Types Contained in the Vaccine
时间窗: Up to ~Month 126
Serum antibody titers (milli Merck Units/mL) measured by cLIA to each of the 9vHPV types were assessed. Per protocol, the extension study included data from 9- to 15-year-old females regardless of lot administered.
Base Study: GMTs for Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Males [Lot 1] and 16- to 26-Year-Old Females [Lot 1])
时间窗: 4 weeks post-vaccination 3 (Month 7)
Serum antibody titers for HPV VLPs, Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using a competitive luminex immunoassay (cLIA). Titers were reported in milli Merck Units/mL.
Base Study: GMTs for Each of the HPV Types Contained in the Vaccine (Lot Consistency Study)
时间窗: 4 weeks post-vaccination 3 (Month 7)
Serum antibody titers for HPV VLPs, Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using cLIA. Titers were reported in milli Merck Units/mL.
Base Study: Percentage of Participants With Body Temperature ≥100.0°F (≥37.8ºC)
时间窗: Up to 5 days after any vaccination
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. The percentage of participants who had at least 1 oral body temperature reading that was ≥100.0°F (≥37.8ºC) was summarized.
Base Study: Percentage of Participants With Injection Site Adverse Experiences (AEs)
时间窗: Up to 5 days after any vaccination
An AE was 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 was also an AE. AEs such as redness, swelling, and pain/tenderness/soreness at the injection site were recorded.
次要结局
- Extension Study: Combined Incidence of HPV 6/11/16/18/31/33/45/52/58-Related Persistent Infection in Males(Up to ~Month 126)
- Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (Lot Consistency Study)(4 weeks post-vaccination 3 (Month 7))
- Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Males [Lot 1] Versus 16- to 26-Year-Old Females [Lot 1])(4 weeks post-vaccination 3 (Month 7))
- Extension Study: Combined Incidence of Cervical Intraepithelial Neoplasia, Vulvar Intraepithelial Neoplasia, Vaginal Intraepithelial Neoplasia, Genital Warts, and Cervical/Vulvar/Vaginal Cancers Related to HPV 6/11/16/18/31/33/45/52/58 in Females(Up to ~Month 126)
- Extension Study: Percentage of Participants With Vaccine-Related or Procedure-Related Serious Adverse Events(Up to ~Month 126)
- Base Study: Percentage of Participants Who Seroconvert to Each of the HPV Types Contained in the Vaccine (9- to 15-Year-Old Females [Lot 1] and 16- to 26-Year-Old Females [Lot 1])(4 weeks post-vaccination 3 (Month 7))
- Extension Study: Combined Incidence of HPV 6/11/16/18/31/33/45/52/58-Related Persistent Infection in Females(Up to ~Month 126)
- Extension Study: Combined Incidence of Penile Intraepithelial Neoplasia, Penile/Perineal/Perianal Cancers and Genital Warts Related to HPV 6/11/16/18/31/33/45/52/58 in Males(Up to ~Month 126)