Sanaria PfSPZ Challenge With Pyrimethamine Chemoprophylaxis (PfSPZ-CVac Approach): Phase 1 Trial to Determine Safety and Protective Efficacy of Sanaria PfSPZ Challenge With Concurrent Pyrimethamine Treatment That Inhibits Development of Asexual B...

Summary

Background: \- Malaria is a severe infection caused by a parasite. People can get malaria if a mosquito that carries the parasite bites them. Although malaria does not occur in the United States, many people in Africa, Asia, and South America do get malaria. In some cases, malaria can cause death. In 2013 alone, 584,000 people died due to malaria. Researchers want to find ways to prevent and treat malaria. Objective: \- To find out if combining live, infectious malaria parasites (known as Sanaria PfSPZ Challenge) and two FDA approved drugs that kill malaria parasites (pyrimethamine \[PYR\] and chloroquine \[CQ\]) is safe and can provide people protection against malaria. The Sanaria PfSPZ Challenge has been used in other studies without significant side effects. Eligibility: * Healthy people ages 18-50 who weigh less than 170 pounds and are not pregnant or breastfeeding * No history of hepatitis B, hepatitis C, or HIV infection * Not currently enrolled in a clinical trial that involves a research drug or vaccine * Have not traveled to an area with high malaria transmission within the last 5 years * Never diagnosed with malaria in the past Design: * Participants will be in 1 of 4 groups. * Participants will receive a combination of injections and drugs. What combination they will receive will depend on what group they are in. This combination of injections and drugs may include: * Injections of Sanaria PfSPZ Challenge (live, infectious malaria parasites) into a vein * FDA approved antimalarial drug called chloroquine (CQ) * FDA approved antimalarial drug called pyrimethamine (PYR) * FDA approved antimalarial drug called Malarone * The study will last approximately 3-7 months (depending on which group participants are in). * There will be up to 68 study visits for three groups. One group will have up to 27 study visits. During the study visits, participants may have: * Medical history review * Physical exams * Electrocardiogram (ECG): soft electrodes will be placed on the skin. A machine will record the heart s electrical signals to evaluate heart function. * Blood and urine tests * Medication given in the clinic under direct observation * Injection of Sanaria PfSPZ Challenge into a vein * Participants will receive a diary, thermometer, and ruler to record their body temperature and any symptoms.

Timeline

Start

2015-07-21

Primary completion

2016-10-21

Completion

2017-06-01

Publications

• 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.
• Background Bijker EM, Bastiaens GJ, Teirlinck AC, van Gemert GJ, Graumans W, van de Vegte-Bolmer M, Siebelink-Stoter R, Arens T, Teelen K, Nahrendorf W, Remarque EJ, Roeffen W, Jansens A, Zimmerman D, Vos M, van Schaijk BC, Wiersma J, van der Ven AJ, de Mast Q, van Lieshout L, Verweij JJ, Hermsen CC, Scholzen A, Sauerwein RW. Protection against malaria after immunization by chloroquine prophylaxis and sporozoites is mediated by preerythrocytic immunity. Proc Natl Acad Sci U S A. 2013 May 7;110(19):7862-7. doi: 10.1073/pnas.1220360110. Epub 2013 Apr 18.
• Background Sheehy SH, Spencer AJ, Douglas AD, Sim BK, Longley RJ, Edwards NJ, Poulton ID, Kimani D, Williams AR, Anagnostou NA, Roberts R, Kerridge S, Voysey M, James ER, Billingsley PF, Gunasekera A, Lawrie AM, Hoffman SL, Hill AV. Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe. PLoS One. 2013 Jun 18;8(6):e65960. doi: 10.1371/journal.pone.0065960. Print 2013.
• 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.

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