Status and phase
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About
This is an open label, Phase 2 study with controlled human malaria infection (CHMI). Twenty three subjects will be enrolled into 2 groups (15 subjects in the Chloroquine-Azithromycin [CQ/AZ] Intervention Group, and 8 subjects in the Chloroquine [CQ] Group). The CQ/AZ Group will receive experimental intervention of 300 mg of CQ and 2 g of azithromycin (AZ). The CQ Group will receive 300 mg of CQ only. All subjects will participate in the CHMI and will be required to stay at a hotel for evaluation for a maximum of 14 nights starting 7 days after the challenge. A standard dose of atovaquone-proguanil (Malarone®) will be administered to all symptomatic parasitemic subjects under directly observed treatment.
Full description
This study is a Phase 2, open-label study of the combination of a single dose-level of AZ (Zithromax) plus CQ given weekly as a prophylaxis against CQ-resistant P falciparum in healthy adults. After signing informed consent, subjects will undergo screening procedures between Day -77 to Day -18. If enrolled, subjects who are still eligible at Study Day -18 will be randomized to either the CQ/AZ group (Group 1 of 15 subjects: 2 g AZ (Zithromax) plus 300 mg CQ base weekly for 6 weeks), or the CQ control group (Group 2 of 8 subjects: 300 mg chloroquine base weekly for 6 weeks) and start intervention on Study Day -17. The rationale for the CQ control group to receive CQ is to show that the strain utilized (7G8) is indeed chloroquine resistant in humans: we expect all of the subjects in the CQ control group to become symptomatically parasitemic. If 3 or more subjects in the CQ control group do not become symptomatic with malaria, the CHMI will be considered uncontrolled either due to 7G8 not being CQ-resistant, or the parasite not being infective.
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Volunteers
Inclusion criteria
Healthy adults (male or non-pregnant, non-lactating female) 18 to 50 years of age (inclusive) at the time of screening.
If the subject is female:
Free of significant health problems as established by medical history, laboratory, and clinical examination before entering the study
Subjects must have low cardiac risk factors according to the NHANES I criteria, medical history and family history, blood pressure measurements, and a normal or normal variant ECG including QTcF no greater than 450 msec for males and 470 msec for females.
Available to participate in all planned study visits and reachable by phone for duration of study (approximately 4 months).
Willing to comply with all protocol procedures and time commitments
No plans to participate in another clinical research study for the duration of this study.
Written informed consent must be obtained from the subject before screening procedures are performed
If a subject is active duty military, he or she must obtain approval from his or her supervisor per Walter Reed Army Institute of Research (WRAIR) Policy 11-45
Subjects must score at least 80% correct on a multiple-choice quiz that assesses their understanding of this study
Exclusion criteria
Subjects with a history or presence of gastrointestinal, hepatic or renal disease, or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
Subjects with a history of retinopathy, sickle cell disease or trait, psoriasis, or porphyria.
Subjects who take certain prescribed or over the counter (OTC) concomitant medication including: ampicillin, antacids (including kaolin), cimetidine, digoxin, ergot alkaloids, statins (HMG-CoA reductase inhibitors), cyclosporine, warfarin, fluconazole, nelfinavir, or rifabutin, within 2 weeks of dosing start, and during the duration of the study.
Are known or suspected of drinking too much alcohol (for men, more than 28 standard alcohol drinks and for women more than 21 standard alcohol drinks per week (standard drink is defined as a 12 oz beer, 5 oz glass of wine, or 1.5 oz of distilled spirit)
Positive urine drug screen for amphetamine, methamphetamine, cocaine, and opioids at screening.
Subjects who have donated more than 1500 mL (males) or 1000 mL (females) blood in the previous 12 months, including the maximum volume of blood (328 mL) to be taken in this study.
Subjects who are currently enrolled in another study involving an investigational product, or if recently involved in another clinical trial which has ended, have not received any investigational products within the past 3 months or 5 half-lives (whichever is longer) from the time of screening.
Any history of malaria infection in the past 3 years.
History of travel to malaria endemic areas in the 3 months prior to day of challenge, or plans to travel to malaria endemic areas during the duration of the study (56 days post challenge).
Any history of receiving a malaria vaccine
History of receipt of malaria prophylaxis during the 2 months prior to day of challenge
History of use of any antibiotics with significant antimalarial activity (examples include tetracycline, doxycycline, clindamycin, azithromycin, and sulfa drugs) during the course of the study period
Pregnant (positive β-human chorionic gonadotropin test, β-HCG) or lactating female at screening or plans to become pregnant or breastfeed from the time of enrollment until three months after challenge
Allergy to antimalarial drugs or use of medications known to interact with CQ
Significant (e.g., systemic) hypersensitivity reactions to mosquito bites (local hypersensitivity reactions at the site of mosquito bites are not an exclusion criterion)
History of splenectomy
Any confirmed or suspected immunodeficiency, including HIV infection, or taking immunosuppressive medications
Acute or chronic, ally significant, pulmonary, cardiovascular, endocrine, hepatic, or renal functional abnormality, as determined by history, physical examination, or laboratory evaluation
Chronic or active neurologic disease including seizure disorder and chronic migraine headaches
Any abnormal baseline laboratory screening tests listed below
Seropositive for Human immunodeficiency virus (HIV) or Hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) positive
An abnormal baseline screening ECG suggestive of cardiac disease as determined by a clinical investigator. QTcF of >450 msec for males and >470 msec for females.
Any other significant finding that in the opinion of the PI would increase the risk of having an adverse outcome from participating in this study
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0 participants in 3 patient groups
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Data sourced from clinicaltrials.gov
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