Chemoprotective Activity of MMV390048 in PfSPZ Challenge Model

Inclusion Criteria: * Completion of written informed consent for study participation by the volunteer * Able and willing to answer all questions on the informed consent quiz correctly, demonstrating an understanding of the study information and of the procedures associated with the study * Men or WONCBP aged ≥ 18 and ≤ 45 at screening * Good health based on the absence of significant medical history and clinically significant findings on physical examination and special investigations at screening and prior to IMP administration * Body mass index \>18 and \< 30 \[kg/m2\] * Negative alcohol breath test and urine drug screening test at screening (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates) and upon admission prior to IMP administration * Sexually active male volunteers with female partners must agree to use a highly effective, medically acceptable form of contraception from the day of IMP administration until 120 days thereafter (covering a full sperm cycle of 90 days starting after 5 x t½ of the drug). Abstinent male volunteers or male volunteers with same-sex partners must agree to use the above-mentioned contraceptive methods if they commence heterosexual relations during the study, and to continue these methods until 120 days after IMP administration. Acceptable methods of contraception include the following: * Condom and occlusive cap (diaphragm or cervical/vault caps) * Surgical sterilization (vasectomy with documentation of azoospermia) plus utilisation of a barrier method (condom or occlusive cap \[diaphragm or cervical/vault caps\]) * The subject's female partner uses contraception known to inhibit ovulation (combined oral oestrogen/progesterone preparation, oral or injectable progesterone, subdermal implants or transdermal contraceptive patch) commenced at least 14 days prior to IMP administration to the male subject plus utilisation of a barrier method (condom or occlusive cap \[diaphragm or cervical/vault caps\] * The subject's female partner has undergone documented bilateral tubal ligation (female sterilization) plus utilisation of a barrier method (condom or occlusive cap \[diaphragm or cervical/vault caps\] * The subject's female partner has undergone documented placement of an intrauterine device or intrauterine system plus utilisation of a barrier method (condom or occlusive cap \[diaphragm or cervical/vault caps\] * Women must be of non-childbearing potential as per one of the following definitions: * surgically sterile (by hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy) as documented by a surgical report or by ultrasound, or * post-menopausal (spontaneous amenorrhoea for ≥ 12 months, or spontaneous amenorrhoea for 6-12 months and follicle-stimulating hormone (FSH) ≥ 40 IU/mL; either should be together with the absence of oral contraceptive use for \> 12 months) * Consent to permit the investigators to discuss the volunteer's medical history with their General Practitioner and to sign a request to release medical information concerning contraindications for participation in the study * Able and willing (in the investigator's opinion) to comply with all study requirements for the duration of the study * Agreement to undergo all study procedures, to attend all study visits and stay overnight for observations as required, up to and including the last follow-up visit * Willingness to undergo a CHMI by DVI with PfSPZ Challenge * Reachable (24/7) by mobile phone or electronic mail during the whole study period * Agreement to refrain from blood donation during the course of the study and after the end of their involvement in the study according to the local and national blood banking eligibility criteria (currently 4 years in Germany) * Willingness to take a curative regimen of artemether-lumefantrine (Riamet®) or another registered antimalarial if necessary Exclusion Criteria: * Any history of malaria * Volunteer has travelled to or lived in a malaria-endemic area for more than 4 weeks during the 12 months prior to IMP administration, or spent any time in an endemic area during the 4 weeks prior to IMP administration * Plans to travel to malaria endemic region during the study period up to last follow-up visit * Plans to travel outside of Germany during the challenge period * Volunteer is unable to be closely followed for social, geographic or psychological reasons * Previous participation in any malaria vaccine or CHMI study * Previous participation in a trial with MMV390048 * Participation in any other clinical study within 30 days or five half-lives of the investigational compound in that study (whichever is longer) prior to IMP administration in this study, or plans to participate in other investigational vaccine/drug research during the study period * Participation in any research study involving blood sampling during the 8 weeks prior to IMP administration. (Volunteers from whom blood was last drawn at least 4 weeks prior to IMP administration, and from whom less than 450 ml of blood was taken during the 8 weeks leading up to the last study-related blood draw, may be considered on a case by case basis by the Investigator.) * Blood product donation to any blood bank during the 8 weeks (whole blood) or 4 weeks (plasma and platelets) prior to IMP administration * Blood loss of more than 100 ml during the 4 weeks prior to IMP administration * Male volunteers with a female partner(s) who is (are) pregnant or lactating at the time of the administration of the IMP * Women of childbearing potential, or nursing (lactating) women * Positive HIV, HBV (seropositive for hepatitis B surface antigen) or HCV tests * Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection, asplenia (e.g. post-splenectomy), recurrent, severe infections, or the use of chronic (more than 14 days) immunosuppressant or immune-modifying drugs within the 6 months prior to IMP administration. (The use of oral antihistamines, topical steroids or inhaled steroids at doses less than the equivalent of 800 ug budesonide or 750 ug fluticasone daily are not classified as immunosuppressant or immune-modifying for the purpose of this criterion.) * History of serious psychiatric condition that may affect participation in the study or preclude compliance with the protocol, including but not limited to past or present psychoses, disorders requiring lithium, a history of attempted or planned suicide, more than one previous episode of major depression, any previous single episode of major depression lasting for or requiring treatment for more than 6 months, or any episode of major depression during the 5 years preceding screening. The Beck Depression Inventory will be used as an objective tool for the assessment of depression at screening. In addition to the conditions listed above, subjects with a score of 20 or more on the Beck Depression Inventory and/or a response of 1, 2 or 3 for item 9 of this inventory (related to suicidal ideation) will not be eligible for participation. Subjects with a Beck score of 17 to 19 may be enrolled at the discretion of the Investigator if they do not have a history of the psychiatric conditions mentioned in this criterion and their mental state is not considered to pose additional risk to the health of the volunteer or to the execution of the study and interpretation of the data gathered * History of convulsions or of severe head trauma * History of frequent headaches (either severe in nature or requiring continuous daily treatment or treatment more than three times per week on average) and/or migraines * A history of clinically significant systemic disorders including haematological, renal, endocrine, gastrointestinal, hepatic, cardiovascular, pulmonary, dermatological, neurological, immunological or other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteers * History of cancer (except localised basal cell carcinoma of the skin) * History of diabetes mellitus * History of asthma * Falling in moderate or higher risk category for a fatal or non-fatal cardiovascular event within 5 years (\> 10%) determined by non-invasive criteria for cardiac risk * History of arrhythmias or documented prolonged QTcB- or QTcF-interval (\> 450 msec), any previous episode of syncope thought to be of cardiac origin, or a family history of long QT syndrome or unexplained sudden death * Positive family history of cardiac disease in first and second degree relatives \< 50 years * Recent (within the last three years) and/or recurrent history of autonomic dysfunction (e.g. recurrent episodes of fainting, palpitations, etc.) * Any surgical or medical condition possibly affecting drug absorption (e.g. cholecystectomy, gastrectomy, bowel disease), distribution, metabolism or excretion * History or presence of diagnosed food or known drug allergies (including but not limited to allergy to any of the antimalarial rescue medications to be used in the study), or history of anaphylaxis or other severe allergic reactions. (Subjects with seasonal allergies that are untreated and asymptomatic at the time of dosing will not be excluded.) * History of psoriasis or porphyria * Sickle cell anaemia or other red blood cell disorders * G6PD deficiency * Symptoms, physical signs and laboratory values suggestive of systemic disorders including haematological, renal, endocrine, gastrointestinal, hepatic, cardiovascular, pulmonary, dermatological, neurological, immunological or other conditions which could interfere with the interpretation of the study results or compromise the health of the volunteers * Resting vital signs (measured after 5 minutes in the supine position) at screening, admission to the CCT, or baseline prior to IMP administration as follows: * Tympanic body temperature ≥ 38.0 °C * SBP ≤ 90 or ≥ 140 mmHg * DBP ≤ 50 or ≥ 90 mmHg * Pulse rate ≤ 40 or ≥ 100 bpm Vital signs measurement may be repeated once in assessing this criterion if the investigator believes that the values from the original measurement were erroneous * Symptomatic postural hypotension at screening, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic blood pressure ≥20 mmHg 2 minutes after changing from a supine to standing position * Clinically significant abnormalities in electrocardiogram at screening, admission to the CCT, or baseline prior to IMP administration as follows: * PR-interval \>210 msec * QRS-complex \>120 msec * QTcB- or QTcF-interval \>450 msec * pathologic Q wave * significant ST-T wave changes * left or right ventricular hypertrophy * non-sinus rhythm except isolated premature atrial contractions * incomplete left bundle branch block, or complete or intermittent right or left bundle branch block * second or third degree A-V heart block The ECG reading may be repeated once in assessing this criterion if the investigator believes that the values from the original reading were erroneous. * Haematology, clinical chemistry, coagulation or urinalysis results at screening or on admission to the CCT prior to IMP administration that are outside of Sponsor-approved clinically acceptable laboratory ranges documented prior to study start or are considered clinically relevant * Contraindications to the use of chloroquine phosphate, atovaquone-proguanil, artemether or lumefantrine * Use of any prescription drugs, herbal supplements (e.g. St John's Wort), or over-the-counter medication within 7 days or five half-lives (whichever is longer) prior to IMP administration, or an anticipated requirement for the use of these during the course of the study. (If necessary, the incidental use of NSAIDs, vitamins and topical treatments may be acceptable after approval by the study Sponsor and will be documented in the case report form \[CRF\]. The use of nutritional supplements during this time that are not believed to have the potential to affect subject safety nor the overall results of the study, may be permitted on a case-by-case basis following approval by the Sponsor in consultation with the Investigator.) * Use of systemic antibiotics with known antimalarial activity within 30 days of IMP administration (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, or azithromycin) or an anticipated requirement for the use of these during the study period * Use of medications known to interact with chloroquine, atovaquone-proguanil (Malarone®) or artemether-lumefatrine (Riamet®) such as cimetidine, metoclopramide or antacids, or an anticipated requirement for the use of these at any point during the study period * Ingestion of any poppy seeds within 24 hours prior to the screening or pre-dose urine drug screen * Intake of grapefruit or grapefruit juice within 5 days of IMP administration, or unwillingness to abstain from the consumption of these products from 5 days prior to IMP administration until collection of the final PK blood sample * Use of immunoglobulins or blood products within 3 months prior to IMP administration * Suspected or known history of, or current alcohol abuse, or heavy intake defined as greater than 28 g (men) or 18 g (women) per day or a carbohydrate deficient transferrin level ≥ 2.5% * Current drug habituation, or suspected or known intravenous drug abuse in the 5 years preceding enrolment * Current smoking of more than 10 cigarettes or equivalent per day and/or unwilling to abstain from smoking during the admission period * Plan for major surgery between enrolment and completion of study follow-up * Personnel (e.g. investigator, sub-investigator, research assistant, pharmacist, study coordinator or anyone mentioned in the delegation log) directly involved in the conduct of the study * The subject has been committed to an institution by virtue of an order issued by either the judicial or administrative authorities