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.

Conditions

• Malaria

Interventions

DRUG

Chloroquine Phosphate

Chloroquine has been widely used for treatment and prophylaxis of malaria since 1946 (Most, London et al. 1984). It was the treatment of choice for uncomplicated malaria for decades because it was safe, well tolerated, affordable and highly effective for the treatment of malaria. However, increasing spread of chloroquine- resistant Pf over the last two decades has severely limited its use (Wellems 2002). Chloroquine phosphate is U.S Food and Drug Administration (FDA) approved for suppressive treatment (prophylaxis) and for acute attacks of malaria due to P. vivax, P. malariae, P. ovale, and susceptible strains of Pf.

DRUG

Pyrimethamine

Pyrimethamine is a folic acid antagonist that has been commonly used as antimalarial drug for both treatment and prevention of malaria, usually in combination with sulfadoxine in adults, pregnant women, and children worldwide (Organization April 2013 (rev. January2014)

BIOLOGICAL

Sanaria PfSPZ Challenge

Sanaria Inc has manufactured two strains of Sanaria PfSPZ Challenge: NF54 and 7G8. The Sanaria PfSPZ Challenge contains fully infectious PfSPZ purified from the salivary glands of Anopheles stephensi mosquitoes raised under aseptic conditions. The infectious PfSPZ are formulated in cryoprotectant to maintain potency for an extended period. Sanaria PfSPZ Challenge (NF54) is known to be susceptible to chloroquine, pyrimethamine, atovaquone, artesunate, but not mefloquine. Sanaria PfSPZ Challenge (7G8) is known to be susceptible to mefloquine, atovaquone, artemether and artesunate but not to chloroquine or pyrimethamine.

Sponsors & Collaborators

• Sanaria Inc.

  collaborator INDUSTRY

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• Patrick E Duffy, M.D. · National Institute of Allergy and Infectious Diseases (NIAID)

Study Design

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2017-06-05

Primary Completion

2019-06-26

Completion

2019-06-26

FDA Drug

Yes

Countries

• United States

Study Locations