Phase 1 Study of the Safety and Immunogenicity of rDEN4delta30-4995, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 4
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 2
- 主要终点
- Frequency of vaccine-related adverse events, graded by severity for each dose
研究概览
简要总结
Dengue fever, which is caused by dengue viruses, is a major health problem in tropical and subtropical regions of the world. The purpose of this study is to evaluate the safety and immune response to the dengue vaccine DEN4delta30-4995 in healthy adults.
详细描述
Dengue viruses account for more than 50 million cases of dengue fever and a half million cases of the more severe disease, dengue hemorrhagic fever/dengue shock syndrome. Infection with dengue viruses is the leading cause of hospitalization and death in children in at least eight Asian countries. The goal of producing a vaccine against dengue fever is to induce a long-lived antibody response against all four dengue serotypes. The rDEN4delta30-4995 vaccine candidate is a live attenuated recombinant virus derived from rDEN4delta30 for protection against dengue virus serotype 4. The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of rDEN4delta30-4995 in healthy adults.
This study will last 180 days (6 months). Participants in Cohort 1 will be randomly assigned to receive the highest dose of rDEN4delta30 or placebo at study entry. Participants in Cohort 2 will be randomly assigned to receive a lower dose of rDEN4delta30 or placebo. Participants in Cohort 3 will be randomly assigned to receive the lowest dose of rDEN4delta30 or placebo. Cohorts 2 and 3 will begin after a safety review of all participants in the previous cohort.
After initial vaccination, participants in Cohort 1 will be followed every other day for the first 16 days of the study, monitoring their temperature three times a day through Day 16 and recording these measurements in a diary. After Day 16, study visits will occur on Days 21, 28, 42, and 180 and will include a physical exam and blood collection. Some participants will also be asked to undergo a skin biopsy or additional blood collection at selected visits.
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
- •Adult males and non-pregnant females between 18 and 50 years of age
- •Good general health
- •Available for the duration of the study
- •Willing to use acceptable methods of contraception for the duration of the study
排除标准
- •Significant neurologic, cardiac, 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
- •Severe asthma
- •HIV-1 serotype infected
- •Hepatitis C virus (HCV) infected
- •Hepatitis B surface antigen positive
- •Immunodeficiency syndrome
- •Use of corticosteroids or immunosuppressive medications within 2 weeks prior to study entry. Individuals 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
- •Prior receipt of yellow fever or dengue vaccine (licensed or experimental)
- •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 affect participation in the study
- •Pregnant or breastfeeding
结局指标
主要结局
Frequency of vaccine-related adverse events, graded by severity for each dose
时间窗: Throughout study
Immunogenicity of the rDEN4delta30-4995 vaccine against DEN4 virus by measurement of plaque reduction neutralization titers (PRNT)
时间窗: At Days 28 and 42
次要结局
- Durability of antibody responses to DEN4 virus(At Month 6)
- Frequency, quantity, and duration of viremia in each dose cohort studied based on the mean peak viremia, mean day onset of viremia, and mean duration of viremia of each dose cohort(Throughout study)
- Number of vaccinees infected with the rDEN4delta30-4995 chimeric vaccine(Throughout study)