Phase II Double-blinded Randomized Controlled Evaluation of MVA85A/AERAS-485 for Safety, Immunogenicity and Prevention of Tuberculosis in BCG-vaccinated, HIV-negative Infants
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 2,797
- 试验地点
- 5
- 主要终点
- To Evaluate the Safety Profile of MVA85A/AERAS-485 in Bacillus Calmette-Guerin (BCG) -Vaccinated, HIV-negative Infants.
研究概览
简要总结
This was a Phase II double-blinded randomized controlled evaluation of safety, immunogenicity and efficacy of MVA85A/AERAS-485 in Bacillus Calmette-Guérin (BCG) vaccinated infants without tuberculosis or HIV infection. This study planned to enroll 2784 infants (126 to 182 days of age) who received study vaccine or control and were followed for 15 - 36 months. The study was conducted at a single site in South Africa.
详细描述
This was a Phase II double-blinded randomized controlled evaluation of safety, immunogenicity and efficacy of MVA85A/AERAS-485 in BCG vaccinated infants without tuberculosis or HIV infection. Infants (126 to 182 days) received intradermal (ID) study vaccine (MVA85A/AERAS-485 or Candida skin test antigen control). All infants were to be followed for at least 15 months after the last infant was enrolled into the study. Given completion of enrollment in 21 months, the total duration of follow-up for each infant was scheduled to be at least 15 months and up to 36 months. Infants were to be followed for the entire duration of the study both for the development of tuberculosis and serious adverse events.
On enrollment to the study, eligible infants were assigned to a study group starting with Study Group 1 and were randomized in a 1:1 ratio within a study group to receive either MVA85A/AERAS-485 or Candida skin test antigen control. Infants were assigned to a safety cohort (Study Group 1), then into 1 of 3 immunological assay evaluation groups (Study Groups 2-4), and finally the remainder of infants were assigned into the correlate of protection cohort (Study Group 5). At least 330 infants were to be randomized in Study Group 1, up to 50-60 infants each in Study Groups 2-4, and the remaining infants were randomized in Study Group 5.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 126 Days 至 182 Days（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age of 126 through 182 days on the day of randomization (Study Day 0)
- •Written informed consent obtained from the parents/guardian
- •Weight: by chart >3rd percentile on Study Day 0 or, if < 3rd percentile, infant has shown a stable growth pattern
- •BCG vaccination within 7 days of birth
- •Generally good health confirmed by medical history and physical examination within 35 days prior to Study Day 0
- •Must have received age-appropriate doses of pneumococcal vaccine as recommended by the South African Department of Health but no injection within 14 day prior to Study Day 0
- •Ability to complete follow-up period as required by the protocol
- •Completed simultaneous enrollment in the Aeras Vaccine Development Registry protocol
排除标准
- •Acute illness on Study Day 0
- •Fever >=37.5 degrees Celsius on Study Day 0
- •Evidence of significant active infection on Study Day 0
- •Received a Expanded Program of Immunization (EPI) within 14 days prior to Study Day 0
- •Historical or virological evidence of individual or maternal human immunodeficiency virus (HIV-1) infection
- •History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine
- •Previous medical history, or evidence, of an intercurrent illness that may compromise the safety of the infant in the study
- •Evidence of chronic hepatitis from any cause
- •History or evidence of any systemic disease on physical examination or any acute, chronic or intercurrent illness that, in the opinion of the investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine
- •History of or known tuberculosis or treatment for tuberculosis
- •Shared residence since birth with an individual with active tuberculosis or on anti-tuberculosis treatment for less than 2 months
结局指标
主要结局
To Evaluate the Safety Profile of MVA85A/AERAS-485 in Bacillus Calmette-Guerin (BCG) -Vaccinated, HIV-negative Infants.
时间窗: AEs recorded 28 days post-vaccination; SAEs recorded for entire study period.
Adverse events (AE) were collected for 28 days after vaccination. The subject's parent or guardian recorded information regarding occurrences of solicited adverse events in diary cards through 7 days after vaccination. Serious adverse events (SAE) were collected from the time of study vaccine dosing throughout the entire study. A safety cohort (the first 330 infants enrolled) also had serum chemistry and hematology testing up to 28 days post-vaccination.
次要结局
- To Evaluate the Immunogenicity of the MVA85A/AERAS-485 Vaccine Compared to Controls as Described by Flow Cytometric Intracellular Cytokine Staining of CD4 and CD8 T Cells.(28 days post-vaccination)
- To Evaluate the Efficacy of the MVA85A/AERAS-485 Vaccine Compared to Controls in Prevention of Tuberculosis Using an Endpoint Derived From Epidemiological Cohort Surveys in BCG Vaccinated Infants.(15 to 36 months post-vaccination)
- To Evaluate the Immunogenicity of the MVA85A/AERAS-485 Vaccine Compared to Controls as Described by the ex Vivo Enzyme Linked Immunospot (ELISPOT) Test Used in Previous MVA85A/AERAS-485 Human Trials.(7 days post-vaccination)
- To Evaluate the Immunogenicity of the MVA85A/AERAS-485 Vaccine Compared to Controls as Described by the University of Capetown (UCT) Whole Blood Intracellular Cytokine Assay.(28 days post-vaccination)
- To Discover Correlates of Protection From Tuberculosis in Infants Vaccinated With MVA85A/AERAS-485.(15 to 36 months post-vaccination)
- To Evaluate the QuantiFERON Conversion Rate at Final Study Assessment in MVA85A/AERAS-485 Recipients Compared to Controls in Infants Without a Diagnosis of Tuberculosis During the Trial.(15 to 36 months post-vaccination)