Inclusion Criteria:
1. In run-in cohort: Male and female patients 12 to \< 18 years of age, with a body weight
* 35.0 kg In Cohort 1: Male and female patients 2 to \< 12 years of age, with a body weight ≥ 10.0 kg In Cohort 2: Male and female patients 6 months to \< 2 years of age, with a body weight
* 5.0 kg
2. Microscopic confirmation of P. falciparum by Giemsa-stained thick and thin films
3. P. falciparum parasitemia of ≥ 1,000 and ≤ 150,000 parasites/μL at the time of prescreening for the Run-in Cohort; and P. falciparum parasitemia of ≥ 1,500 and ≤ 150,000 parasites/μL at the time of pre-screening for Cohorts 1 and 2
4. Axillary temperature ≥ 37.5 ºC or oral/tympanic/rectal temperature ≥ 38.0 ºC; or history of fever during the previous 24 hours (at least documented verbally)
5. Written informed consent has been obtained from parent / legal guardian before any assessment is performed. If the parent/legal guardian is unable to read and write, then a witnessed consent according to local ethical standards is permitted. Patients who are capable of providing assent, must provide assent with parental/legal guardian consent or as per local ethical guidelines
6. The patient and his/her parent/legal guardian is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions and is likely to complete the study as planned
Exclusion Criteria:
1. Mixed Plasmodium infections as per light microscopy results
2. Signs and symptoms of severe malaria according to WHO 2015 (see Section 16.4)
3. Significant, non-plasmodial co-infections including tuberculosis
4. Patients with concurrent febrile illnesses (e.g., typhoid fever, known or suspected COVID19)
5. Known relevant liver disease e.g. chronic hepatitis, cirrhosis, compensated or decompensated, history of hepatitis B or C, hepatitis B or A vaccination in last 3 months, known gallbladder or bile duct disease, acute or chronic pancreatitis
6. Major congenital defects
7. Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection or family history of congenital or hereditary immunodeficiency
8. Immunosuppressive therapy (steroids, immune modulators or immune suppressors) within 3 months prior to recruitment. (For corticosteroids, this will mean prednisone, or equivalent, ≥ 0.5 mg/kg/day. Inhaled and topical steroids are allowed)
9. Repeated vomiting (defined as more than 3 times in the 24 hours prior to inclusion in the study) or severe diarrhea (defined as more than 3 watery stools in the 24 hours prior to inclusion in the study)
10. Active duodenal ulcer, ulcerative colitis, Crohn's disease, chronic (i.e., \> 2 weeks) use of non-steroidal anti-inflammatory drugs (NSAIDs)
11. Clinically relevant abnormalities of electrolyte balance which require correction, e.g., hypokalemia, hypocalcemia or hypomagnesemia
12. Anemia (hemoglobin level \<7 g/dL)
13. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs (e.g., HIV patients on ART therapy or TB patients on treatment), or which may jeopardize the patient in case of participation in the study. The investigator should make this determination in consideration of the patient's medical history and/or clinical or laboratory evidence of any of the following:
* AST/ALT \> 3 x the upper limit of normal range (ULN), regardless of the level of total bilirubin
* AST/ALT \> 1.5 and ≤ 2 x ULN and total bilirubin is \> ULN Total bilirubin \> 2 x ULN regardless of the level of AST/ALT
14. Resting QT interval corrected by Fridericia's formula (QTcF) \> 450 ms at screening
15. Creatinine \> 2 x ULN in the absence of dehydration. In case of dehydration, creatinine should be \< 2 x ULN after oral/parenteral rehydration
16. Any severe disease condition which might prohibit participation in this study
17. Known chronic underlying disease such as sickle cell disease, and severe cardiac, renal, or hepatic impairment
18. Known active or uncontrolled thyroid disease
19. Inability to swallow oral medication (in tablet and/or liquid form)
20. Patients with prior antimalarial therapy or antibiotics with antimalarial activity within minimum of their five (5) plasma half-lives (or within 4 weeks of screening if half-life is unknown)
21. Use of other investigational drugs within 30 days of dosing or until the expected pharmacodynamic effect has returned to baseline, whichever is longer
22. Patients taking medications prohibited by the protocol
23. Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance within 3 months of dosing
24. History or family history of long QT syndrome or sudden cardiac death, or any other clinical condition known to prolong the QTc interval, such as history of symptomatic cardiac arrhythmias, clinically relevant bradycardia or severe heart disease
25. Use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of study
26. History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes
For the Run-in Cohort only:
27. Pregnant or nursing (lactating) patients
28. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of investigational drug. Basic contraception methods include:
* Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
* Male sterilization (at least 6 m prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient
* Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps).
Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking investigational drug. Women are considered not of child bearing potential if they have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
For Cohorts 1 and 2 only:
29. Patients of child bearing potential, defined as all girls post first menarche (except for Run-in Cohort)
