Dose Escalation PfSPZ-CVac

Summary

Background: People get malaria from bites from infected mosquitos. Researchers are studying a vaccine strategy. They will give people malaria parasites by injecting them with live infectious malaria parasites with antimalarial medications and then see if this strategy prevents malaria infection while off antimalarial medications. Objective: To see if combining a high dose of live, infectious malaria parasites (known as Sanaria PfSPZ Challenge) and two FDA approved drugs that kill malaria parasites (pyrimethamine \[PYR\] OR chloroquine \[CQ\]) is safe and can provide people protection against malaria. Eligibility: Healthy adults ages 18-50 who: * are not pregnant or breastfeeding or planning on becoming pregnant while in the study * are not infected with HIV, Hepatitis B or Hepatitis C * have reliable early morning access to the NIH Clinical Center * are able to come to the outpatient clinic frequently, sometimes daily * have not been diagnosed with malaria within the past 10 years Design: * Participants will be screened with medical history and physical exam. They will have heart, blood, and urine tests. * Participants will have blood drawn for tests at most visits. * Participants will keep track of their temperature and symptoms during some sections of the study. * Participants will join one part of the study. Part 1 is one month: * Participants will get the parasites by an injection into a vein on day 1 and receive antimalarial medications. * They will have daily visits on days 7-14 * They will take another antimalarial at visits on days 15-17. * The final visit will be on day 29. Part 2 is seven months: * For the first 3 months, participants will get the parasite injection into a vein for 3 injections in total. Each injection will occur once per month while taking an antimalarial drug. * They will have daily visits on days 7-14 after the first injection, and on days 7-11 after the second and third injection. * They will have a final (fourth) injection around month 6 without any antimalarial medication. * After this fourth injection, participants may have up to 21 daily visits from day 7 after injection until end of study. Part 3 is one month: * Participants will get the parasites by injection into a vein on day 1 without antimalarial medications. * They will have visits almost every day starting day 7 from injection. * They will take an antimalarial medication when they are diagnosed with malaria * They will return for final end of study visit on days 27-29.

Timeline

Start

2017-06-05

Primary completion

2019-06-26

Completion

2019-06-26

Publications

• Background Bijker EM, Borrmann S, Kappe SH, Mordmuller B, Sack BK, Khan SM. Novel approaches to whole sporozoite vaccination against malaria. Vaccine. 2015 Dec 22;33(52):7462-8. doi: 10.1016/j.vaccine.2015.09.095. Epub 2015 Oct 23.
• Background Mordmuller B, Supan C, Sim KL, Gomez-Perez GP, Ospina Salazar CL, Held J, Bolte S, Esen M, Tschan S, Joanny F, Lamsfus Calle C, Lohr SJ, Lalremruata A, Gunasekera A, James ER, Billingsley PF, Richman A, Chakravarty S, Legarda A, Munoz J, Antonijoan RM, Ballester MR, Hoffman SL, Alonso PL, Kremsner PG. Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection: a dose-finding trial in two centres. Malar J. 2015 Mar 18;14:117. doi: 10.1186/s12936-015-0628-0.
• Background Roestenberg M, McCall M, Hopman J, Wiersma J, Luty AJ, van Gemert GJ, van de Vegte-Bolmer M, van Schaijk B, Teelen K, Arens T, Spaarman L, de Mast Q, Roeffen W, Snounou G, Renia L, van der Ven A, Hermsen CC, Sauerwein R. Protection against a malaria challenge by sporozoite inoculation. N Engl J Med. 2009 Jul 30;361(5):468-77. doi: 10.1056/NEJMoa0805832.
• Mwakingwe-Omari A, Healy SA, Lane J, Cook DM, Kalhori S, Wyatt C, Kolluri A, Marte-Salcedo O, Imeru A, Nason M, Ding LK, Decederfelt H, Duan J, Neal J, Raiten J, Lee G, Hume JCC, Jeon JE, Ikpeama I, Kc N, Chakravarty S, Murshedkar T, Church LWP, Manoj A, Gunasekera A, Anderson C, Murphy SC, March S, Bhatia SN, James ER, Billingsley PF, Sim BKL, Richie TL, Zaidi I, Hoffman SL, Duffy PE. Two chemoattenuated PfSPZ malaria vaccines induce sterile hepatic immunity. Nature. 2021 Jul;595(7866):289-294. doi: 10.1038/s41586-021-03684-z. Epub 2021 Jun 30.

Drugs

Indications