Double Blind Dose-Escalating Randomized Controlled Phase 1 Study in Malaria Exposed Adults of the Safety and Immunogenicity of Pfs25-EPA/ Alhydrogel, a Transmission Blocking Vaccine Against Plasmodium Falciparum in Bancoumana, Mali
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 230
- 试验地点
- 1
- 主要终点
- Incidence of local and systemic adverse events and serious adverse events.
研究概览
简要总结
Background:
- Malaria is a disease that is spread by mosquitoes. Researchers are looking for a vaccine that can prevent mosquitoes from transmitting malaria to people. They want to test a vaccine called Pfs25-EPA/Alhydrogel that may help stop malaria parasites from developing in mosquitoes. When a mosquito bites a vaccinated person, the vaccine should prevent parasites from developing in the mosquito. As a result, the mosquito will not spread malaria to the next person it bites. However, the vaccine will not directly prevent people vaccinated from getting sick with malaria. Researchers want to test this vaccine in people who live in rural Mali. To do so, the study will compare the symptoms and the blood tests of the participants who receive either the study vaccine or a regular hepatitis B/meningococcal vaccine.
Objectives:
- To see if Pfs25-EPA/Alhydrogel is a safe and effective malaria vaccine.
Eligibility:
- Healthy volunteers between 18 and 45 years of age who live in Bancoumana, Mali.
Design:
- Participants will be screened with a medical history, physical exam, and blood tests.
- Participants will be separated into two groups. One group will have Pfs25-EPA/Alhydrogel to test the study vaccine. The other group will have the regular Hepatitis B vaccine series, meningococcal vaccine.
- In the study vaccine group, participants will have either a lower dose or a higher dose. For the lower dose, they will have two vaccine shots over 1 year. For the higher dose, they will have four vaccine shots over about 14 months.
- In the other vaccine group, participants will have the Hepatitis B vaccine series, meningococcal vaccine according to the standard dose schedule.
- All participants will provide regular blood samples for testing during the study.
- Participants who develop malaria during the study will participate in evaluation of transmission and parasite development of malaria parasite from the person to mosquito via transmission assays. They will allow mosquitoes (that have no diseases) to bite them in a controlled clinic setting. This will let researchers see if the vaccine can stop the mosquitoes from carrying malaria to other people.
详细描述
A vaccine to interrupt malaria transmission would be a valuable tool for local elimination or eradication of this disease. Pfs25, a surface antigen of ookinetes in the mosquito stage of P. falciparum, is a lead candidate for a malaria transmission blocking vaccine. Recombinant Pfs25 has been conjugated to Pseudomonas aeruginosa ExoProtein A (EPA), and adjuvanted with Alhydrogel . This dose escalating, double-blind, randomized controlled trial will determine safety and immunogenicity of the vaccine in malaria exposed adults. One hundred twenty (120) subjects will be enrolled and randomized to receive the low dose (16 g of conjugated Pfs25, n=10), the high dose (47 g of conjugated Pfs25, n=50), or the comparator vaccine (Euvax B for first 3 vaccinations, then Menactra vaccine for the fourth vaccination, n=10 for 2 vaccinations, n=50 for 4 vaccinations). Enrollment within the high dose group will be staggered for additional safety. The low dose and the matching comparator cohort (Group 1) will receive 2 vaccine doses given at 0 and 2 months. For the rest of the subjects, 3 doses will be given at a 0, 2, 4 month dosing intervals, and a fourth (booster) dose will be given 12 months following the third dose at the start of the subsequent transmission season. Subjects will be followed for 12 months following the last vaccination. Safety outcomes will be local and systemic adverse events (AEs) and serious adverse events (SAEs). Immunogenicity outcomes will be antibody responses as measured by ELISA against recombinant Pfs25 and EPA, and B cell responses. Functional activity of the induced antibody will be assessed by direct transmission blocking assays (direct skin feeds, direct membrane feeding assays) conducted at the Malaria Research and Training Center (MRTC) in Mali and in a standard membrane feeding assay conducted at the National Institute of Allergy and Infectious Diseases (NIAID) in the United States.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Group 1
Group 1: n=20, randomized to receive 16 g Pfs25-EPA/Alhydrogel (n=10) or the comparator (EuvaxB, n=10) on D0, D56
干预措施: Pfs25-EPA/Alhydrogel (Biological)
Group 1
Group 1: n=20, randomized to receive 16 g Pfs25-EPA/Alhydrogel (n=10) or the comparator (EuvaxB, n=10) on D0, D56
干预措施: Euvax B (Biological)
Group 2
Group 2: n=30, randomized to receive 47 g Pfs25-EPA/Alhydrogel (n=15) or the comparator (EuvaxB and Menactra , n=15) on D0, D56, D112, D480
干预措施: Pfs25-EPA/Alhydrogel (Biological)
Group 2
Group 2: n=30, randomized to receive 47 g Pfs25-EPA/Alhydrogel (n=15) or the comparator (EuvaxB and Menactra , n=15) on D0, D56, D112, D480
干预措施: Euvax B (Biological)
Group 2
Group 2: n=30, randomized to receive 47 g Pfs25-EPA/Alhydrogel (n=15) or the comparator (EuvaxB and Menactra , n=15) on D0, D56, D112, D480
干预措施: Menactra (Biological)
Group 3
Group 3: n=70 randomized to receive 47 g Pfs25-EPA/Alhydrogel (n=35) or the comparator (EuvaxB and Menactra , n=35) on D0, D56, D112, D480
干预措施: Pfs25-EPA/Alhydrogel (Biological)
Group 3
Group 3: n=70 randomized to receive 47 g Pfs25-EPA/Alhydrogel (n=35) or the comparator (EuvaxB and Menactra , n=35) on D0, D56, D112, D480
干预措施: Euvax B (Biological)
Group 3
Group 3: n=70 randomized to receive 47 g Pfs25-EPA/Alhydrogel (n=35) or the comparator (EuvaxB and Menactra , n=35) on D0, D56, D112, D480
干预措施: Menactra (Biological)
结局指标
主要结局
Incidence of local and systemic adverse events and serious adverse events.
时间窗: 12 months following the last vaccination; and for 6 months following the fourth vaccination.
次要结局
- Antibody responses as measured by ELISA against recombinant Pfs25 and EPA, and B cell responses. Functional activity of the induced antibody will be assessed by direct transmission blocking assays(12 months following the last vaccination; and for 6 months following the fourth vaccination.)