Study of the Safety and Immunogenicity of Pfs230D1M-EPA/Alhydrogel and Pfs25M-EPA/Alhydrogel , a Transmission Blocking Vaccine Against Plasmodium Falciparum Malaria, in Adults in the U.S. and Mali
- Conditions
- Malaria
- Interventions
- Registration Number
- NCT02334462
- Brief Summary
Background:
- Malaria is a severe infection caused by a parasite. People can get malaria if a mosquito that carries the parasite bites them. Malaria infection does not happen in the United States, but many people in Africa, Asia, and South America are at risk for it. Researchers want to test two vaccines that may help decrease malaria infection.
Objective:
- To see if two vaccines (Pfs25M-EPA/Alhydrogel and Pfs230DIM-EPA/Alhydrogel ) are safe in humans and cause an immune response that will prevent malaria parasites from correctly growing in the mosquito.
Eligibility:
- Healthy adults ages 18 50.
Design:
* There are several groups in this study. Each group will receive a different dose of the vaccine and some groups will received both vaccines.
* Vaccinations will be given on two days about 4 weeks apart.
* Participants will receive each vaccine as an injection into the arm. Blood will be drawn on the day of vaccination.
* In the 4 weeks after receiving a vaccination, participants will have at least 3 clinic visits and 1 phone contact. They will have at least 3 more visits and 3 phone contacts over the next 6 months.
* At each visit, participants will be evaluated for side effects to the vaccine and any new health changes or problems. They will be asked how they are feeling and if they have taken any medicine. Blood and urine samples may be taken at the visit. More follow-up visits may be needed to follow up on changes or problems.
- Detailed Description
A vaccine to interrupt malaria transmission would be a valuable tool for local elimination or
eradication of this disease. Pfs25 and Pfs230, surface antigens of zygotes and ookinetes in the mosquito stage of Plasmodium falciparum, are the lead candidates for a malaria transmission blocking vaccine. Recombinant Pfs25M and recombinant Pfs230D1M have each been conjugated to Pseudomonas aeruginosa ExoProtein A (EPA) and adjuvanted with Alhydrogel . This dose-escalating phase 1 study will determine safety and immunogenicity of these vaccines in US adults and subsequently in Malian adults.
A total of 260 subjects will be enrolled at sites in the US and Mali to receive escalating doses of Pfs25M- EPA/Alhydrogel , Pfs230D1M-EPA/Alhydrogel , or simultaneous Pfs25MEPA/Alhydrogel and Pfs230D1M-EPA/Alhydrogel . Enrollment within each group will be staggered for additional safety, and subjects will only be enrolled into the simultaneous administration group once each individual dose has been administered and reviewed for safety. Subjects will be followed for at least 6 months after 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, Pfs230, and EPA, and B cell responses. Functional activity of the induced antibodies will be assessed by membrane feeding assays conducted at the National Institute of Allergy and Infectious Diseases in the US.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 538
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1-U.S Pfs25M-EPA/Alhydrogel Arm 1a (N=5) to receive 16 micrograms Pfs25M on D0, D28. Arm 1b (N=5) to receive 47 micrograms Pfs25M on D0, D28. Group 3- Mali Pfs25M-EPA/Alhydrogel Arm C1 (N=5) to receive 16 micrograms Pfs25M and 15 micrograms Pfs230D1M on D0, D28Arm C2 (N=50) to receive 47 micrograms Pfs25M and 40 microgramsPfs230D1M on D0, D28, D168, D530 Group 3- U.S. Pfs25M-EPA/Alhydrogel Arm 3a (N=5) to receive 16 micrograms Pfs25M and 15 micrograms Pfs230D1M on D0, D28. Arm 3b (N=5) to receive 47 micrograms Pfs25M and 40 micrograms Pfs230D1M on D0, D28. Group 2- Mali Pfs230D1M-EPA/Alhydrogel Arm B1 (N=5) to receive 15 micrograms Pfs230D1M on D0, D28 Pfs230D1M-EPA/Alhydrogel Arm B2 (N=50) to receive 40 micrograms Pfs230D1M and Normal Saline on D0, D28, D168, D530 Group 2-U.S Pfs230D1M-EPA/Alhydrogel Arm 2a (N=5) to receive 5 micrograms Pfs230D1M on D0, D28.Arm 2b (N=5) to receive 15 micrograms Pgs230D1M on D0, D28. Arm 2c (N=5) to receive 40 micrograms Pfs230D1M on D0, D28. Group 1- Mali Pfs25M-EPA/Alhydrogel Arm A1 (N=5) to receive 16 micrograms Pfs25M on D0, D28 Arm A2 (N=50) to receive 47 micrograms Pfs25M and Normal Saline on D0, D28, D168, D530 Group 3- Mali Pfs230D1M-EPA/Alhydrogel Arm C1 (N=5) to receive 16 micrograms Pfs25M and 15 micrograms Pfs230D1M on D0, D28Arm C2 (N=50) to receive 47 micrograms Pfs25M and 40 microgramsPfs230D1M on D0, D28, D168, D530 Group 3- U.S. Pfs230D1M-EPA/Alhydrogel Arm 3a (N=5) to receive 16 micrograms Pfs25M and 15 micrograms Pfs230D1M on D0, D28. Arm 3b (N=5) to receive 47 micrograms Pfs25M and 40 micrograms Pfs230D1M on D0, D28. Group 4- Mali TWINRIX Arm D1 (N=5) to receive TWINRIX on D0, D28Arm D2 (N=5) to receive TWINRIX and NormalSaline on D0, D28Arm D3 (N=50) to receive TWINRIX and NormalSaline on D0, D28, D168; to receive Menactra andNormal Saline on D530 Group 4- Mali Menactra Arm D1 (N=5) to receive TWINRIX on D0, D28Arm D2 (N=5) to receive TWINRIX and NormalSaline on D0, D28Arm D3 (N=50) to receive TWINRIX and NormalSaline on D0, D28, D168; to receive Menactra andNormal Saline on D530
- Primary Outcome Measures
Name Time Method Incidence of local and systemic adverse events and serious advents in U.S. adults and in exposed Malian adults. U.S. Study: Days 1,3,7,14,28,29,31,35,42,56,84,112,140,168 and 196. Same as U.S. plus Days 169,171,175,182,189,196,203,210,217,240,2 70,300,330,360,390,420,450,480,510,540,541,543,547,554,561,568,575,582,589,610,640,670,700,730
- Secondary Outcome Measures
Name Time Method Anti -Pfs25 and Anti-Pfs230 antibody levels elicited by as measured by ELISA in U.S. adults and in exposed Malian adults U.S. Study: D. 14,28,42,84,140,196 Mali (Safety Arm: Same as the U.S. Mali (Functional Arm): D. 14,28,42,84,140,168,182,196,210,240,300,360,420,480,540,554,568,582,610,670,730
Trial Locations
- Locations (2)
Malaria Research and Training Center
🇲🇱Bamako, Mali
National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸Bethesda, Maryland, United States