Efficacy, Safety and Tolerability of KAF156 in Combination With Lumefantrine Solid Dispersion Formulation (LUM-SDF) in Pediatric Population With Uncomplicated Plasmodium Falciparum Malaria

Inclusion Criteria

• In run-in cohort: Male and female patients 12 to 2 weeks) use of non-steroidal anti-inflammatory drugs (NSAIDs)
• Clinically relevant abnormalities of electrolyte balance which require correction, e.g., hypokalemia, hypocalcemia or hypomagnesemia
• Anemia (hemoglobin level 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
• Resting QT interval corrected by Fridericia's formula (QTcF) > 450 ms at screening
• Creatinine > 2 x ULN in the absence of dehydration. In case of dehydration, creatinine should be < 2 x ULN after oral/parenteral rehydration
• Any severe disease condition which might prohibit participation in this study
• Known chronic underlying disease such as sickle cell disease, and severe cardiac, renal, or hepatic impairment
• Known active or uncontrolled thyroid disease
• Inability to swallow oral medication (in tablet and/or liquid form)
• 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)
• Use of other investigational drugs within 30 days of dosing or until the expected pharmacodynamic effect has returned to baseline, whichever is longer
• Patients taking medications prohibited by the protocol
• Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance within 3 months of dosing
• 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
• Use of agents known to prolong the QT interval unless it can be permanently discontinued for the duration of study
• 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:

• Pregnant or nursing (lactating) patients
• 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