MMV390048 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Participants

Inclusion Criteria: * Participants who do not live alone from Day 0 until at least the end of the antimalarial drug treatment, and are contactable and available for the duration of the trial (≤4 months) * Body weight ≥50kg, body mass index between 18.0 and 32.0 kg/m2, inclusive * Healthy by clinical assessment * Normal vital signs * Normal 12-lead electrocardiogram * Lab tests in normal range * Agrees to use a double barrier method of contraception including condom plus diaphragm or condom plus intrauterine device or condom plus stable oral / transdermal / injectable hormonal contraceptive by female partner for ≥14 days prior to the first dose of study drug until 90 days after the last dose * Written informed consent before any study procedure Exclusion Criteria: * History of malaria or participation in a previous malaria challenge study * Must not have travelled to or lived \>2 weeks in a malaria-endemic area in past 12 months nor plan to travel to one during study * Evidence of increased cardiovascular disease risk * History of splenectomy * Presence / history of drug hypersensitivity, or allergic disease diagnosed and treated or history of a severe allergic reaction, anaphylaxis or convulsions following any vaccination or infusion * Presence of current / suspected serious chronic diseases such as cardiac or autoimmune disease, diabetes, progressive neurological disease, severe malnutrition, acute or progressive hepatic or renal disease, psoriasis, rheumatoid arthritis, asthma, epilepsy or obsessive compulsive disorder, skin carcinoma excluding non-spreadable skin cancers such as basal cell and squamous cell carcinoma, schizophrenia, bi-polar disease, or other severe (disabling) chronic psychiatric diagnosis * History of photosensitivity * History of schizophrenia, bi-polar disease, or other severe (disabling) chronic psychiatric diagnosis, including depression or receiving psychiatric drugs or hospitalized in past 5 yrs for psychiatric illness, history of suicide attempt or confinement for danger to self/others * Frequent headache and/or migraine, recurrent nausea, and/or vomiting (≥2 / month) * Acute infectious disease/fever in 5 days pre-inoculation with malaria parasites * Acute illness in 4 weeks pre-screening which may compromise subject safety * Any significant intercurrent disease, in particular liver, renal, cardiac, pulmonary, neurologic, rheumatologic, or autoimmune disease by history, physical exam or lab test * Clinically significant disease or any condition that might affect drug absorption distribution or excretion * Participation in any investigational study in last 12 weeks * Any blood sampling/donation in last 8 weeks * Unwilling to defer blood donation for 6 months * Any blood donation, in 1 month before inclusion. * Medical requirement for intravenous immunoglobulin or blood transfusion * Ever had a blood transfusion * Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension * History or presence of alcohol abuse (≥40g per day) or drug habituation, or any prior intravenous use of an illicit substance * Smoking ≥5 cigarettes or equivalent /day and unable to stop smoking during confinement period * Poppy seeds in 24h pre-screening * Excessive consumption of xanthine bases, including red bull, chocolate * Any medication (including St John's Wort) in 14 days pre-study or within 5 times the medication half-life if longer * Vaccination in the last 28 days * Any corticosteroids, anti-inflammatory, immunomodulators or anticoagulants. Any currently or previous immunosuppressive therapy, including systemic steroids including adrenocorticotrophic hormone or inhaled steroids in dosages associated with hypothalamic-pituitary-adrenal axis suppression or chronic use of inhaled high potency corticosteroids * Recent or current systemic therapy with an antibiotic / potential antimalarial * Likely to be noncompliant, or unable to cooperate * Not contactable in case of emergency throughout and for 2 weeks after end of study * Staff directly involved in study conduct * Without good peripheral venous access * Positive for: hepatitis B surface antigen, anti-hepatitis B core antibodies, anti-hepatitis C virus antibodies, or anti-human immunodeficiency virus 1/2 antibodies * glucose-6-phosphate dehydrogenase deficiency * Positive urine drug screen or alcohol urine or breath test * Cardiac/QT risk: Known pre-existing prolongation of the QTcB/QTcF interval considered clinically significant. Family history of sudden death or of congenital prolongation of the corrected QT interval interval or known congenital prolongation of the corrected QT interval or any clinical condition known to prolong the corrected QT interval interval. History of symptomatic cardiac arrhythmias or with clinically relevant bradycardia. Electrolyte disturbances, particularly hypokalaemia, hypocalcaemia or hypomagnesaemia. Clinically relevant 12-lead electrocardiogram abnormality at screening or which will interfere with the analysis, or history of clinically significant abnormalities * Known hypersensitivity to MMV390048 or any of its excipients or 4-aminoquinolines, artemether or other artemisinin derivatives, lumefantrine, or other arylaminoalcohols * Unwillingness to abstain from citrus (grapefruit, Seville orange, etc.) or juice, as well as quinine containing foods/beverages for the study period * Lactose intolerance * Unwilling to restrict exposure to direct sunlight during the study. Must use sunglasses and sunblock for the study period