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.

Conditions

• Malaria

Interventions

DRUG

Chloroquine (CQ)

Chloroquine Phosphate is a 4-aminoquinoline compound that is commercially available for oral administration. It is a white, odorless, bitter tasting, crystalline substance freely soluble in water; and widely used for the treatment andprophylaxis of malaria. It is supplied and manufactured in tablets of 500 mg (equivalent to 300 mg chloroquine phosphaste base)

DRUG

Pyrimethamine (PYR)

PYR is a folic acid antagonist that is commercially available; and 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. It is manufactured in tablets of 25 mg.

BIOLOGICAL

Sanaria PfSPZ Challenge (NF54)

Sanaria PfSPZ Challenge are aseptic, cryopreserved P.falciparum sporozoites used for CHMI trials, produced by the biotechnology company; Sanaria Inc. In brief, manufacture includes the production, under traditional environmental conditions, of eggs from a colony of A. stephensi mosquitoes housed in a controlled environmental chamber. The sporozoites are purified, counted, and, at a specified concentration, cryopreserved. Cryopreservation commences with the addition of cryoprotective additives to the purified sporozoites to produce the Sanaria PfSPZ Challenge product. Sanaria PfSPZ Challenge is dispensed into screw-cap vials containing 15,000, 50,000, or 100,000 PfSPZ in a 20 L aliquot. Sanaria PfSPZ Challenge is stored in liquid nitrogen vapour phase at 140 (Infinite)C to -196 (Infinite)C.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• Sara A Healy, 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

2015-07-21

Primary Completion

2016-10-21

Completion

2017-06-01

Countries

• United States

Study Locations