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Protocol Details

Sanaria PfSPZ Challenge with Pyrimethamine Chemoprophylaxis (PfSPZ-CVac Approach): Phase 1 Dose Escalation Trial to Determine Safety and Development of Protective Efficacy after Exposure to Only Pre-erythrocytic Stages of Plasmodium falciparum

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

17-I-0067

Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18
Max Age: 50

Referral Letter Required

No

Population Exclusion(s)

Pregnant Women and Fetuses;
Children

Special Instructions

Currently Not Provided

Keywords

Malaria;
Parasitemia;
Immune;
Responses;
Sporozoites

Recruitment Keyword(s)

None

Condition(s)

Malaria

Investigational Drug(s)

Sanaria PfSPZ Challenge

Investigational Device(s)

None

Intervention(s)

Drug: Chloroquine Phosphate
Drug: Pyrimethamine
Biological/Vaccine: Sanaria PfSPZ Challenge

Supporting Site

National Institute of Allergy and Infectious Diseases

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.

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Eligibility

INCLUSION CRITERIA:

-Age greater than or equal to 18 and less than or equal to 50 years.

-In good general health and without clinically significant medical history

-Malaria comprehension exam completed, passed (a score of greater than or equal to 80% or per investigator s discretion) and reviewed prior to enrollment

-Reliable access to the clinical trial center and availability to participate for duration of study

-Females of childbearing potential must be willing to use reliable contraception (as defined below) from 21 days prior to study day -2 to 28 days following last Sanaria PfSPZ Challenge exposure

-Subject to the judgment and discretion of the PI, female participants who meet ANY ONE of the criteria listed immediately below, may not be required to take any additional measures to avoid pregnancy. Such participants will be counseled on risks at the time of consent and at appropriate points (e.g. when pregnancy testing occurs) during the study:

--Females who have had their uterus, and/or BOTH ovaries removed

--Females who have had BOTH fallopian tubes surgically 'tied' or removed

--Females who are above the age of 45 and have spontaneously had no menses at any point during the past 12 or more consecutive months (i.e. have reached menopause)

--Females who, in the conservative and reasonable judgment of the PI (e.g. due to sexual orientation or serious life choice (such as being celibate clergy or transgender), during the entire trial will NOT participate in any potentially reproductive sexual contact

--Females who, in the conservative and reasonable judgment of the PI, are in a monogamous stable relationship with a male who has undergone vasectomy at least 4 months prior or another procedure/medical condition that deems the male sterile

-Subject to the judgment and discretion of the PI, female participants who DO NOT meet ANY of the criteria listed above, will be appropriately counseled on reproductive risks and pregnancy avoidance, and will be required to adhere to the following measures and agree to 2 methods of pregnancy prevention as noted below:

--CATEGORY 1: a highly effective hormonal method to prevent pregnancy [e.g. CONSISTENT, CONTINUOUS use of contraceptive pill, patch, ring, implant or injection], and/or IUD or equivalent

--IN ADDITION TO CATEGORY 2: a barrier method to be used at the time of potentially reproductive sexual activity (e.g. [male/female condom, 'cap,' or diaphragm] + spermicide).

EXCLUSION CRITERIA:

-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

-Clinically significant medical condition, physical examination findings, other clinically significant abnormal laboratory results, or past medical history that may have clinically significant implications for current health status and participation in the study in the opinion of the Investigator. A clinically significant condition or process includes but is not limited to:

--A process that would affect the immune response, or requires medication that affects the immune response

--Any contraindication to repeated phlebotomy

--A condition or process in which signs or symptoms could be confused with reactions to malaria challenge and/or infection, including dermatologic abnormalities at the site of sporozoite inoculation

--A chronic or subclinical condition which could be exacerbated by administration of any of the PfSPZ-CVac components or malaria infection

-History of, or known active cardiac disease including: (1) prior myocardial infarction (heart attack); (2) angina pectoris; (3) congestive heart failure; (4) valvular heart disease; (5) cardiomyopathy; (6) pericarditis; (7) stroke or transient ischemic attack; (8) exertional chest pain or shortness of breath; or ( 9) other heart conditions under the care of a doctor

-Clinically significant ECG findings, as determined by the expert study cardiologist

-Moderate or high risk for coronary heart disease (CHD) based on NHANES I cardiovascular risk assessment

-Acute illness at the time of enrollment

-Infection with HIV, Hepatitis B, Hepatitis C

-Psychiatric condition that precludes compliance with the protocol including but not limited to:

--Psychosis within the past 3 years

--Ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years

-Suspected or known current alcohol or drug abuse as defined by the American Psychiatric Association in the DSM V at the discretion of the PI

-Clinical trial staff and/or Sanaria Inc. employees with direct involvement in the conduct of the trial are excluded from participation.

-Participating in other clinical trials involving investigational interventions or off label medication use during the study period (excluding participation in the optional long term follow up visits). Participation in other trials such as observational or imaging studies will be discussed with the investigators.

-Any other finding that, in the judgment of the Investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a subject s ability to give informed consent, or increase the risk of having an adverse outcome from participating in the study.


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Citations:

Bijker EM, Borrmann S, Kappe SH, Mordm(SqrRoot) ller B, Sack BK, Khan SM. Novel approaches to whole sporozoite vaccination against malaria. Vaccine. 2015 Dec 22;33(52):7462-8. doi: 10.1016/j.vaccine.2015.09.095.

Mordm(SqrRoot) ller B, Supan C, Sim KL, G(SqrRoot)>=mez-P(SqrRoot)(Copyright)rez GP, Ospina Salazar CL, Held J, Bolte S, Esen M, Tschan S, Joanny F, Lamsfus Calle C, L(SqrRoot)(Delta)hr SJ, Lalremruata A, Gunasekera A, James ER, Billingsley PF, Richman A, Chakravarty S, Legarda A, Mu(SqrRoot) oz J, Antonijoan RM, Ballester MR, Hoffman SL, Alonso PL, Kremsner PG. Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection: a dose-finding trial in two centres. Malar J. 2015 Mar 18;14:117. doi: 10.1186/s12936-015-0628-0.

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, R(SqrRoot)(Copyright)nia 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.

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Contacts:

Principal Investigator

Referral Contact

For more information:

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



Patrick E. Duffy, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
BG 29B RM 4NN06
9000 ROCKVILLE PIKE
BETHESDA MD 20814
(301) 761-5089
duffype@niaid.nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT03083847

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