Dose Escalation PfSPZ-CVac

Completed · Phase 1

Conditions studied: Malaria

In brief

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.

Key facts

Study ID

NCT03083847

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

55

Starts

2017-06-05

Expected to finish

2019-06-26

Last updated by the study team

2021-06-01

Who can join

Age: 18 and older, up to 50. Sex: any. Healthy volunteers: accepted.

You may not qualify if…

• Currently is breast-feeding (if female).
• Pregnancy as determined by a positive urine or serum human choriogonadotropin (beta- hCG) test at any point during the study (if female).
• Recent travel to a malaria endemic area within 5 years of enrollment (Endemic areas are defined per the CDC website. Factors such as but not limited to use of antimalaria prophylaxis during travel, length of stay, activities during the travel, history of illnesses within 30 days of travel will be considered to determine the likelihood that the subject was exposed to malaria)
• Planned travel to a malaria endemic area (as defined by the Center for Disease Control) during the study period
• Reported history of confirmed malaria diagnosis on peripheral blood smear or by clinical history in the past 10 years.
• Hemoglobin, WBC, platelets, ALT, and creatinine outside of local lab normal range (subjects may be included at the investigator s discretion for not clinically significant values outside of normal range)
• Abnormal urinalysis as defined by positive urine glucose, protein, and red blood cells. Subject can be included if investigator determine the abnormality is not clinically significant .
• BMI < 17 or BMI > 35
• Anticipated use during the study period, or use within the following periods prior to enrollment:
• Investigational malaria vaccine within the last five years
• Malaria chemoprophylaxis within 6 months
• Chronic systemic immunosuppressive medications (>14 days) within 6 months (e.g.cytotoxic medications, oral/parental corticosteroids >0.5 mg/kg/day prednisone or equivalent). Corticosteroid nasal spray for allergic rhinitis and topical corticosteroids for mild, uncomplicated dermatitis are allowed.
• Blood products or immunoglobulins within 6 months
• Systemic antibiotics with antimalarial effects within 30 days (such as clindamycin, doxycycline)
• Investigational or non-registered product or vaccine within 30 days
• Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to Sanaria PfSPZ Challenge
• Medications known to interact with pyrimethamine and/or chloroquine (for the main and pilot study participants ONLY), atovaquone, proguanil (ALL participants)
• Reported history of:
• Sickle cell disease, sickle cell trait, or other hemoglobinopathies
• Splenectomy or functional asplenia
• Systemic anaphylaxis
• Any allergic reactions to study drugs (pyrimethamine, chloroquine) or NSAIDs, atovaquone, proguanil
• Documented history of chronic or active neurologic disease (including seizures, uncontrolled migraine headaches)
• Psoriasis or porphyria
• Ocular diseases including retinopathy or visual field defects

Where it is running

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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