Phase 1 Study of the Safety and Immunogenicity of rDEN3/4delta30(ME), a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 3
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 2
- 主要终点
- Immunogenicity, as determined by anti-DEN3 neutralizing antibody measured on Days 0, 21, 28, 42, and 180
研究概览
简要总结
Dengue fever, caused by dengue viruses, is a major health problem in the tropical and subtropical regions of the world. The purpose of this study is to test the safety of and immune response to a new dengue virus vaccine in healthy adults.
详细描述
Dengue viruses, which cause dengue fever and dengue shock syndrome, are a major cause of morbidity and mortality in several of the world's tropical and subtropical regions. The rDEN3/4delta30(ME) vaccine is a live attenuated dengue virus vaccine that may be protective against dengue virus serotype 3 (DEN3). The purpose of this study is to evaluate the safety and immunogenicity of the rDEN3/4delta30(ME) vaccine in healthy adults.
This study will last 40 weeks. Participants will be randomly assigned to receive one of three doses of rDEN3/4delta30(ME) or placebo. Participants in Group 1 will receive the middle dose of rDEN3/4delta30(ME) or placebo at study entry. Group 2a will begin enrollment after the immunogenicity review of all participants in Group 1. Participants in Group 2a will receive the highest dose of rDEN4delta30(ME) or placebo at study entry. Group 2b will begin enrollment after the immunogenicity review of all participants in Group 2a. Participants in Group 2b will receive the lowest dose of rDEN4delta30(ME) or placebo.
After vaccination, participants in all groups will be followed closely every other day for the first 16 days of the study. Participants will take their temperature three times a day through Day 16 and record each measurement in a diary. After Day 16, participants will have study visits on Days 21, 28, 42, and 180; a physical exam and blood collection will occur at all visits. Some participants may be asked to join a skin biopsy substudy.
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
- •Good general health
- •Available for the duration of the study
- •Willing to use acceptable forms of contraception for the duration of the study
排除标准
- •Significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
- •Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may interfere with the study
- •Significant laboratory abnormalities
- •Medical, work, or family problems as a result of alcohol or illegal drug use within 12 months prior to study entry
- •History of severe allergic reaction or anaphylaxis
- •Emergency room visit or hospitalization for severe asthma within 6 months prior to study entry
- •HIV-1 infected
- •Hepatitis C virus (HCV) infected
- •Hepatitis B surface antigen positive
- •Immunodeficiency syndrome
- •Use of corticosteroids or immunosuppressive medications within 30 days prior to study entry. Participants using topical or nasal corticosteroids are not excluded.
- •Live vaccine within 4 weeks prior to study entry
- •Killed vaccine within 2 weeks prior to study entry
- •Absence of spleen
- •Blood products within 6 months prior to study entry
- •Previous dengue virus or other flavivirus (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus) infection
- •Previously received yellow fever or dengue vaccine
- •Plans to travel to an area where dengue infection is common
- •Received an investigational agent within 30 days prior to 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
Immunogenicity, as determined by anti-DEN3 neutralizing antibody measured on Days 0, 21, 28, 42, and 180
时间窗: Throughout study
Safety, as defined by frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance
时间窗: Throughout study
次要结局
- Determine the number of vaccinees infected with rDEN3/4delta30(ME)(Throughout study)
- Determine cellular targets of vaccine infection, including peripheral blood mononuclear cells (PBMCs) and skin from participants who are willing to undergo skin biopsy(Throughout study)
- Assess the frequency, quantity, and duration of viremia in each dose cohort studied(Throughout study)
- Compare the infectivity rates, safety, and immunogenicity between dose groups(At study completion)
- Evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy(Throughout study)