Phase I/II Study of Safety and Immunogenicity of Quadrivalent Meningococcal Conjugate Vaccine (MCV4) in HIV-Infected Children and Youth And Open Label Immunogenicity Study of a Booster Dose of MCV4 in Previously Immunized HIV-Infected Children and Youth
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 384
- 试验地点
- 71
- 主要终点
- Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4.
研究概览
简要总结
Bacterial meningitis infection is common in youth 2 to 24 years of age in the United States. This disease can be treated by antibiotics, but mortality rates associated with meningitis of up to 53% have been estimated. Vaccination against meningitis may be effective in preventing this disease, especially for HIV-infected youth who have weakened immune systems. The purpose of this study was to determine the safety of and immune response to a preventive meningitis vaccine in HIV-infected youth.
详细描述
In the United States, youth 2 to 24 years of age are at high risk for bacterial meningitis infection. Despite antibiotic treatment, the mortality rate for meningitis and sepsis can reach as high as 53% caused by Neisseria meningitidis. This rate could be higher in immunocompromised individuals, such as those infected with HIV. To prevent infection, vaccination against meningitis is recommended by the CDC at ages 11, 15, and 18. The quadrivalent meningococcal conjugate vaccine (MCV4) is a vaccine that has been observed to elicit an appropriate immune response to N. meningitidis and was approved by the FDA in January 2005. However, to date, no studies have been done to determine the safety and immunogenicity of this vaccine in HIV-infected individuals. The purpose of this study was to determine the safety and immunogenicity of MCV4 in HIV-infected youth 2 to 24 years of age.
The study was originally designed for participants to be followed for 72 weeks. Participants were enrolled in three groups by age and CD4% as follows:
Group 1: Age 11 to 24 years, CD4% of 15% or higher. Enrollment was further stratified by CD4%: 15% to <25%, and >= 25%.
Group 2: Age 11 to 24 years, CD4% < 15%.
Group 3: Age 2 to 10 years, CD4% of 25% or higher.
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
- 2 Years 至 24 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Number of Immunogenic Responders, With Response Defined as a 4-fold or Greater Increase in Serum Bactericidal Antibody Titers From Study Entry to Week 28 After 2 Doses of MCV-4.
时间窗: Study entry and Week 28
Serum bactericidal antibody titers were measured at study entry and Week 28 for each of the four serogroups in the MCV-4 vaccine. Response was defined as a 4-fold or greater increase from entry at Week 28.
Long-term Immunogenicity, as Assessed by Number of Participants With Protective Levels of Antibody at Week 72
时间窗: Week 72
Protective levels of antibody are titers ≥1:128.
Number of Participants With Immunogenicity at Step 3 Entry
时间窗: At 3.5 years (Step 3 entry)
Immunogenicity was assessed for each serogroup by the number of participants with protective antibody levels (titers greater than or equal to 1:128)
Number of Participants With Short-term Immunogenicity, Defined as Number of Seroconverters at Week 4 (Those With at Least a 4-fold Rise in Meningococcal Serum Bactericidal Titers From Baseline)
时间窗: At Study entry, Week 4
Serum bactericidal antibody titers were measured at study entry and Week 4 for each of the four serogroups in the MCV-4 vaccine. Response (seroconversion) was defined as a 4-fold or greater increase from entry at Week 4.
Number of Participants With Grade 3 or Higher Adverse Events Within 42 Days Following Dose 1 of the Vaccine.
时间窗: From administration of Dose 1 at week 0 to 42 days post-vaccination
Adverse events were graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December, 2004, Clarification August 2009, which is available on the RSC web site (http://rsc.tech-res.com/safetyandpharmacovigilance/). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death.
Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Dose 2 of the Vaccine.
时间窗: From administration of Dose 2 at week 24 to 6 weeks post-vaccination
Adverse events were graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December, 2004, Clarification August 2009, which is available on the RSC web site (http://rsc.tech-res.com/safetyandpharmacovigilance/). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death.
Number of Participants With 4-fold Memory Response in Step 3
时间窗: Step 3 entry and Week 1 post-booster vaccine
Defined for each serogroup as a four-fold rise in antibody titers between booster dose (week 0) and week 1.
Number of Participants With Seropositive Memory Response (in Step 3)
时间窗: Step 3 entry and Week 1 post-booster vaccine
Seropositive memory response was defined for each serogroup by having protective antibody levels (titer \>= 1:128) on Day 0 or change from seronegative to seropositive between booster dose (Day 0) and Day 7.
Number of Participants With Immunogenicity at Step 3 Weeks 4 and 24
时间窗: At Step 3 Weeks 4 and 24 post-booster vaccine
Immunogenicity was assessed by the number of participants with protective levels of antibody (titers greater than or equal to 1:128)
Number of Participants With Primary Response (in Step 3)
时间窗: Step 3 entry and Week 4 post-booster vaccine
Primary response was defined for each serogroup as a four-fold rise in Ab concentration between day 0 and day 28, but not between day 0 and day 7; OR a change from seronegative on day 0 to seropositive on day 28, but not between day 0 and day 7. Note: a primary response can only occur in the absence of any memory response.
次要结局
- Immunogenic Response to Serogroup C in Group 2(At Weeks 4, 28, and 72)
- Immunologic Memory or Primary Response for Serogroup C by Treatment Arm(At Week 4 post-booster vaccination)
- Safety, as Assessed by Number of Participants With Reactions and Grade 3 or Higher Adverse Events Within 42 Days Following Step 3 Dose of the Vaccine.(From administration of vaccination at Step 3 entry through 6 weeks post-vaccination)
- Number of Participants With Protective Antibody Titers for Serogroup C at Step 3 Entry(At 3.5 years)
- Immunologic Memory for Serogroup C by Treatment Arm (1 vs. 2 Doses)(At Week 1 post-booster vaccination)