Phase 1 Study of the Safety and Immunogenicity of a 2-Dose Regimen of West Nile/Dengue 4-3'delta30 Chimeric Virus Vaccine (WN/DEN4delta30), a Live Attenuated Vaccine for West Nile Encephalitis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 4
- 主要终点
- Frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance
研究概览
简要总结
West Nile (WN) virus infection is an emerging disease. Infection with WN virus may lead to paralysis, coma, and death. The purpose of this study is to determine the safety of and immune response to a two-dose regimen of a WN vaccine in healthy adults. The vaccine is based on a live attenuated vaccine developed against dengue virus.
详细描述
WN is widely distributed in Africa and Europe, where it is usually associated with mild illness. In the United States, WN is considered a public health threat because severe illness caused by WN infection has caused paralysis, coma, and death, especially in the elderly. This study will evaluate the safety and immunogenicity of a live attenuated chimeric virus, WN/DEN4delta30, which is derived from the DEN4 dengue virus and wild-type WN serotypes.
This study will last at least 32 weeks. Participants in Cohort 1 will be randomly assigned to receive 1X10^4 plaque-forming units (PFU) WN/DEN4delta30 or placebo at study entry and Day 180. Cohort 2 will be randomly assigned to receive a higher dose of WN/DEN4delta30, 10^5 PFU, or placebo at study entry and Day 180. Immediately after receiving their injections, participants will be observed for 30 minutes for immediate adverse reactions.
After each vaccination, participants will be asked to monitor their temperatures three times every day for 16 days. Study visits will occur every other day after each vaccination until Day 16, followed by three additional visits at selected days through Day 180 post-vaccination. Blood collection, medical history, vital signs measurement, and a targeted physical exam will occur at all visits. Participants will also be required to keep temperature diaries until Day 16 after vaccination. Female participants will have a urine pregnancy test performed within 60 days of study entry, and on Days 28, 42, 150, 180, 208, and 222. Pregnancy prevention counseling will occur 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
- •Good general health
- •Available for the duration of the trial
- •Willing to use acceptable forms of contraception for the duration of the study
排除标准
- •Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
- •Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the ability of the volunteer to understand and cooperate with the study
- •Neutropenia (abnormally low neutrophil count)
- •Alcohol or drug abuse within 12 months prior to study entry
- •Elevated levels of alanine aminotransferase (ALT) and serum creatinine
- •History of severe allergic reaction or anaphylaxis
- •Severe asthma
- •HIV-1 infected
- •Hepatitis C virus infected
- •Hepatitis B surface antigen positive
- •Known immunodeficiency syndrome
- •Use of corticosteroids or immunosuppressive drugs within 30 days of study entry. Participants who have used 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
- •Surgical removal of spleen
- •Blood products within 6 months prior to study entry
- •History of dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus)
- •Previously received a licensed or experimental yellow fever or dengue vaccine
- •Investigational agent within 30 days of study entry
- •Other condition that, in the opinion of the investigator, would affect the participant's participation in the study
- •Pregnancy or breastfeeding
结局指标
主要结局
Frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance
时间窗: Throughout study
Immunogenicity, determined by anti-WN/DEN4 neutralizing antibody titer
时间窗: At study entry, Days 28 and 42 after first vaccination, and Days 180, 208, and 222 after second vaccination
次要结局
- Assess the frequency, quantity, and duration of viremia after each dose of vaccine by dose cohort (10^4 or 10^5 PFU)(Throughout study)
- Determine the number of vaccinees infected with WN/DEN4delta30 in each dose cohort (10^4 or 10^5 PFU)(Throughout study)
- Compare the infectivity rates, safety, and immunogenicity between dose 1 and dose 2 within a cohort and between cohorts(At study completion)