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...

2015-07-29 14:08:21 | BioPortfolio



- 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.


- 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.


- 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


- 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.


Human studies have shown that immunization by the bite PfSPZ-infected mosquitoes under drug coverage with chloroquine, an approach called chemoprophylaxis with sporozoites (CPS), infection treatment vaccination (ITV), or chemoprophylaxis vaccination (CVac) can provide high level, long term protection against homologous controlled human malaria infection (CHMI). The Sanaria PfSPZ-CVac approach duplicates this with an injectable sporozoite (SPZ) regimen (aseptic, purified, cryopreserved SPZ). In both approaches, whether mosquitoes or a syringe are used for SPZ administration, when chloroquine is used as the chemoprophylactic agent, transient, limited, asexual erythrocytic stage (AES) parasitemia develops. However, exposure to liver stage parasites only, without having any parasites completing liver stage development and entering the blood, thereby reducing the potential to induce blood stage immunity, likewise has been shown in animal studies to induce protective immunity upon subsequent challenge with homologous parasites, indicating that the transient parasitemia is not integral to inducing protection. To achieve this requires a different partner drug regimen that includes activity against liver stage parasites.

Our approach, using PfSPZ-CVac with pyrimethamine (PYR), will assess this in humans. This phase 1 study will investigate the safety, tolerability, immunogenicity, and protective efficacy following liver stage only parasite exposure of direct venous inoculation (DVI) with aseptic, purified, cryopreserved Plasmodium falciparum (Pf) sporozoites (Sanaria PfSPZ Challenge), under chloroquine and pyrimethamine chemoprophylaxis, to induce stage specific sterile protection.. By adding pyrimethamine chemoprophylaxis to chloroquine, liver stages will develop but should be killed before merozoites are released into the blood stream. The subjects will thus be exposed only to liver stage parasites (qRT-PCR and blood smear negative). With this strategy, we will determine if protective immunity can develop without exposure to AES parasites and additionally whether it will minimize clinical symptoms associated with blood stage exposure. The timing of the pyrimethamine dose is critical to ensure the efficacy of pyrimethamine as causal prophylaxis, yet still allow for maximal antigenic exposure of liver-stage parasites to the host. An additional potential benefit of preventing AES parasitemia is the elimination of the immunosuppression associated with AES parasitemia.

This trial will be the first step in establishing a new regimen for the PfSPZ-CVac approach, exposure to liver stage parasites without subsequent blood stage parasites, assessing protection against homologous CHMI. In future trials, the two-drug regimen which can be assessed for protection against heterologous Pf infection and longevity of protection. The results of the study will contribute to understanding the targets and mechanisms of immunity against Pf malaria infection.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention




Chloroquine (CQ), Pyrimethamine (PYR), Sanaria PfSPZ Challenge (NF54)


National Institutes of Health Clinical Center, 9000 Rockville Pike
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2015-07-29T14:08:21-0400

Clinical Trials [780 Associated Clinical Trials listed on BioPortfolio]

Sanaria PfSPZ Challenge With Pyrimethamine or Chloroquine Chemoprophylaxis Vaccination (PfSPZ-CVac Approach): A Trial to Determine Safety and Protective Efficacy Against Natural Plasmodium Falciparum Infection in Bancoumana and Surrounding Areas, Mal...

Background: Malaria remains a global health problem. Malaria is spread by the bite of mosquitos. Africa is the region where most people get malaria in Africa. Sanaria PfSPZ Challenge is a...

Safety and Protective Efficacy of IV Immunization With Cryopreserved PfSPZ Under A/P Chemoprophylaxis

Single center, randomized, placebo-controlled, double-blinded trial using PfSPZ Challenge (NF54) under A/P chemoprophylaxis for immunization and PfSPZ Challenge (NF54) for repeat CHMI. ...

PfSPZ Challenge in Healthy Malaria-Naïve Adults in the United States

This phase 1, double-blinded, randomized, placebo-controlled study will enroll 36 healthy volunteers to receive 1 of 3 regimens of PfSPZ or placebo, randomized 3:1. They will also receive ...

PfSPZ Challenge With Prophylaxis in Mali

Single site, double-blinded, randomized, placebo-controlled clinical trial of PfSPZ-CVac safety, tolerability, immunogenicity and efficacy against naturally occurring malaria in malaria-ex...

Sequential Optimization of Dose and Schedule of PfSPZ Vaccine

MAVACHE is a sequential dose and schedule optimization trial of intravenous immunization with PfSPZ Vaccine in 18 to 54 malaria-naïve, healthy adult volunteers receiving 9x10^5, 1.35x10^6...

PubMed Articles [3854 Associated PubMed Articles listed on BioPortfolio]

Monocyte phagocytosis of malaria β-haematin in the presence of artemisinin, amodiaquine, chloroquine, doxycycline, primaquine, pyrimethamine and quinine.

The intraerythrocytic malaria parasite digests haemoglobin to provide amino acids for metabolism and releases toxic haem that is sequestered into haemozoin, a non-toxic, insoluble, crystalline pigment...

Development and Evaluation of a Novel HNB Based Isothermal Amplification Assay for Fast Detection of Pyrimethamine Resistance (S108N) in .

Sulphadoxine and pyrimethamine (SP) have been used as long-acting partner antimalarial drugs in artemisinin combination therapy (ACT) for falciparum malaria. The emergence and increasing spread of SP ...

Chloroquine analogs as antimalarial candidates with potent in vitro and in vivo activity.

In spite of recent efforts to eradicate malaria in the world, this parasitic disease is still considered a major public health problem, with a total of 216 million cases of malaria and 445,000 deaths ...

Development of artemisinin resistance in malaria therapy.

Malaria affects 200 million people worldwide. Today, the most successful treatments are artemisinin-based combination therapies (ACT). Resistance has already been described for the elder anti-malarial...

Targeting Asexual and Sexual Blood Stages of Human Malaria Parasite P. falciparum with 7-Chloroquinoline based 1,2,3-Triazoles.

Novel 4-amino-7-chloroquinoline and [1,2,3]-triazole based hybrids were synthesized in good to excellent yields via Cu[I] catalysed Huisgen 1,3-dipolar cycloaddition of 2-azido-N-(7-chloroquinolin-4-y...

Medical and Biotech [MESH] Definitions

A synthetic TETRACYCLINE derivative with similar antimicrobial activity. Animal studies suggest that it may cause less tooth staining than other tetracyclines. It is used in some areas for the treatment of chloroquine-resistant falciparum malaria (MALARIA, FALCIPARUM).

Malaria caused by PLASMODIUM VIVAX. This form of malaria is less severe than MALARIA, FALCIPARUM, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day.

A sulfone active against a wide range of bacteria but mainly employed for its actions against MYCOBACTERIUM LEPRAE. Its mechanism of action is probably similar to that of the SULFONAMIDES which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with PYRIMETHAMINE in the treatment of malaria. (From Martindale, The Extra Pharmacopoeia, 30th ed, p157-8)

Vaccines made from antigens arising from any of the four strains of Plasmodium which cause malaria in humans, or from P. berghei which causes malaria in rodents.

A protozoan parasite that causes vivax malaria (MALARIA, VIVAX). This species is found almost everywhere malaria is endemic and is the only one that has a range extending into the temperate regions.

More From BioPortfolio on "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..."

Quick Search


Relevant Topics

Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...

Tropical Medicine
Tropical Medicine is the study of diseases more commonly found in tropical regions than elsewhere. Examples of these diseases are malaria, yellow fever, Chagas disease, Dengue, Helminths, African trypanosomiasis, Leishmaniasis, Leprosy, Lymphatic filaria...

Searches Linking to this Trial