Phase I Study of the Safety and Immunogenicity of rDEN1delta30, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 1
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Determine the frequency of vaccine related AEs for each dose graded by severity
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 test the safety of and immune response to a new dengue virus vaccine in healthy adults.
详细描述
More than 2 billion people living in tropical and subtropical regions of the world are at risk of dengue virus infection. Dengue viruses cause dengue fever, as well as the more severe dengue hemorrhagic fever/shock syndrome, and dengue virus infection is the leading cause of hospitalization and death in children in several tropical Asian countries. This study will evaluate the safety and immunogenicity of a live, attenuated dengue virus called rDEN1delta30, which is derived from the Western Pacific DEN1 serotype.
This study will last 180 days. Participants in Cohort 1 will be randomly assigned to receive rDEN1delta30 or placebo at study entry. Cohort 2 will begin only after safety review of all participants in Cohort 1. Participants in Cohort 2 will receive a higher dose of rDEN1delta30 or placebo.
After vaccination, participants will be asked to monitor their temperature every day for 16 days. Study visits will occur every other day after vaccination until Day 16, followed by 4 additional visits at selected days through Day 180. Blood collection and a targeted physical exam will occur at each study visit. Some participants will 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
- •Willing to be followed for the duration of the study
- •Willing to use acceptable methods of contraception
- •Good general health
排除标准
- •Clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal 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
- •Liver, renal, or hematologic disease
- •Alcohol or drug abuse within 12 months of study entry
- •History of severe allergic reaction or anaphylaxis
- •Emergency room visit or hospitalization for severe asthma within 6 months of study entry
- •HIV-1 infected
- •HCV 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 of study entry
- •Killed vaccine within 2 weeks of study entry
- •Blood products within 6 months of study entry
- •Investigational drugs or vaccines within 60 days prior to study entry or while currently enrolled in this clinical trial
- •Previously received a licensed or experimental yellow fever or dengue vaccine
- •Surgical removal of spleen
- •History of dengue virus infection or other flavivirus infection
- •Other condition that, in the opinion of the investigator, would affect the participant's participation in the study
- •Pregnancy or breastfeeding
- •Plan to travel to an area where dengue infection is common
研究组 & 干预措施
1
One subcutaneous vaccination with rDEN1delta30 vaccine (10^3 PFU dose) into the deltoid region of either arm.
干预措施: rDEN1delta30 (Biological)
2
One subcutaneous vaccination with rDEN1delta30 vaccine (10^5 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the effect of the vaccine on subjects in Arm 1.
干预措施: rDEN1delta30 (Biological)
3
One subcutaneous vaccination with placebo into the deltoid region of either arm.
干预措施: Placebo (Biological)
结局指标
主要结局
Determine the frequency of vaccine related AEs for each dose graded by severity
时间窗: Throughout study
Determine the amount of dengue 1 neutralizing antibody induced by the vaccine
时间窗: At Day 42
次要结局
- To assess the durability of the antibody response(At Day 180)
- To assess the frequency, quantity, and duration of viremia in each dose cohort studied(Throughout study)
- To compare the T cell mediated immune response against dengue viruses of those volunteers infected with the rDEN1delta30 vaccine virus with that of uninfected volunteers and placebo recipients(Throughout study)
- If both doses of vaccine are administered, to compare the infectivity rates, safety, and immunogenicity between dose groups(At study completion)
- To evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy(Throughout study)