Evaluation of the Safety and Immunogenicity of Heterologous Dengue Vaccine Administration in Dengue Immune Individuals
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Number, severity, and seriousness of vaccine-related adverse events observed through active and passive surveillance
研究概览
简要总结
Dengue fever, which is caused by dengue viruses, is a major health problem in subtropical regions of the world. There are four different forms (serotypes) of dengue virus that can cause dengue fever. The purpose of this study is to determine the safety and immune response to a vaccine containing a particular dengue serotype when an individual has been previously vaccinated with a different dengue serotype.
详细描述
The World Health Organization estimates that dengue virus causes more than 50 million cases of dengue fever a year. Dengue virus infection is the leading cause of hospitalization and death in children of most tropical Asian countries. There are four different serotypes of dengue virus. Most cases of dengue hemorrhagic fever/dengue shock syndrome are caused by secondary infection with a dengue serotype different from the first serotype the individual was infected with. A vaccine that would be effective in preventing infection by multiple dengue serotypes is desirable. The purpose of this study is to determine the safety of and immune response to two different dengue virus vaccines in individuals who have been previously vaccinated against a different serotype.
This study will last at least 42 days. Participants will be recruited from a database of previous dengue vaccine recipients and will be stratified by the type of vaccine previously received. Participants assigned to Cohort 1 and Cohort 2 will have already been vaccinated with the rDEN4delta30 vaccine. Participants assigned to Cohort 3 will have already been vaccinated with the rDEN2/4delta30(ME) vaccine. Participants in Cohort 4 will have already been vaccinated with the rDEN1delta30 vaccine. Participants in Cohorts 1 and 3 will be randomly assigned to receive either the rDEN1delta30 vaccine or placebo. Participants in Cohorts 2 and 4 will be randomly assigned to receive either the rDEN2/4delta30(ME) vaccine or placebo.
Participants will receive their assigned vaccination on Day 0. Study visits will occur every other day until Day 16, and then at Days 21, 28, and 42. At each visit, blood collection, vital signs measurement, and a physical exam will occur. In addition, participants will be asked to monitor their temperature daily, 3 times a day, from Day 0 to Day 16. Patients will also be asked to enroll in an optional skin biopsy sub-study.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Previous vaccination with rDEN1delta30, rDEN2/4delta30(ME), OR rDEN4delta30 vaccine
- •General good health
- •Available for the duration of the study
- •Willing to use accepted forms of contraception
排除标准
- •Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease by history, physical examination, or laboratory studies including urinalysis
- •Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may interfere with the study
- •Certain abnormal laboratory values
- •Medical, work, or family problems as a result of alcohol or illegal drug use within 12 months of study entry
- •History of severe allergy or anaphylaxis
- •Severe asthma requiring an emergency room visit or hospitalization within 6 months of study entry
- •HIV infected
- •Hepatitis C virus infected
- •Hepatitis B surface antibody positive
- •Known immunodeficiency syndrome
- •Use of corticosteroids or immunosuppressive drugs 30 days prior to study entry. Participants who have used topical or nasal corticosteroids are not excluded.
- •Receipt of live vaccine within 4 weeks of study entry
- •Receipt of killed vaccine within 2 weeks of study entry
- •Absence of spleen
- •Plan to travel to an area where dengue virus is common
- •Any investigational product within 30 days of study entry
- •Other condition that, in the opinion of the investigator, would interfere with the study
- •Pregnancy or breastfeeding
结局指标
主要结局
Number, severity, and seriousness of vaccine-related adverse events observed through active and passive surveillance
时间窗: Throughout study
Neutralizing antibody to all four dengue serotypes
时间窗: At Days 0, 28, and 42
次要结局
- To determine if cellular targets of vaccine infection, including peripheral blood mononuclear cells and skin, are different after heterologous infection of a second dengue virus vaccine of a different serotype(Throughout study)
- Compare the safety and immunogenicity between each heterologous dengue vaccine virus cohort(At study completion)
- Assess the frequency, quantity, and duration of viremia in each vaccine cohort studied(Throughout study)
- Evaluate the immunopathological mechanism of heterologous vaccine virus associated rash in those volunteers who are willing to undergo skin biopsy(Throughout study)
- Characterize the antibody response after heterolouous vaccine infection(Throughout study)