LXE408 for Treatment of Visceral Leishmaniasis in Ethiopia, a Proof of Concept Study

Inclusion Criteria: Written informed consent must be obtained before any study protocol specific assessment is performed, other than procedures performed as part of standard of care. Written informed consent must be signed by adult patients and by a parent or legal guardian for patients under 18 years of age In the case of minors, assent from the adolescent also needs to be obtained Primary symptomatic VL (defined as typical parameters including, but not limited to, fever for >2 weeks, weight loss and splenomegaly) Visualization of Leishmania amastigotes by microscopy in tissue samples (spleen or bone marrow) Exclusion Criteria: Clinical signs of severe VL (including for example jaundice, spontaneous bleeding, oedema, ascites, coma, organ failure) Laboratory abnormalities including ALT/SGPT >3 times ULN, total bilirubin >1.5 times ULN, creatinine >1.5 times ULN, serum amylase or lipase >1.5 times ULN, haemoglobin <6 g/dL or other clinically significant abnormal laboratory parameters which, in the opinion of the investigator, may indicate severe VL Patients with history of visceral leishmaniasis and confirmed relapse Patients with para-kala-azar dermal leishmaniasis Patients with severe malnutrition (for patients ≥15-<18 years: Mid-Upper Arm Circumference (MUAC) cut-off based on MUAC-for-height reference table; for patients ≥18 years: MUAC <170 mm) History of congenital or acquired immunodeficiency, including positive HIV (test at screening), as these patients present lower efficacy rates, higher toxicity and higher lethality compared to non-HIV patients, requiring different case management and care ECG abnormalities, either historic (no longer present) or current which, in the view of the investigator, indicate a significant risk to study participation. These include, but are not limited to, the following: Clinically significant cardiac arrhythmias (e.g., sustained ventricular tachycardia and clinically significant second- or third-degree AV block without a pacemaker) QTcF ≥ 450 ms History of familial long QT syndrome or known family history of Torsades de Pointes Resting heart rate (physical exam or 12 lead ECG) <60 bpm Concomitant known infections, including tuberculosis, severe malaria and any other serious underlying disease that may interfere with disease assessment (e.g., cardiac, renal, hepatic, haematologic and pancreatic) Infection with hepatitis B (HBV) or hepatitis C virus (HCV). Patients with a positive HBV surface antigen (HBsAg) test, or if standard local practice, a positive HBV core antigen test, and patients with a positive HCV antibody test must be excluded and will be followed up as per local practice. Known history of hearing impairment and/or clinical signs and symptoms of hearing impairment identified during routine physical examination Patients with previous history of hypersensitivity reaction or known drug class allergy to any of the study treatments or excipients Pregnant or nursing (lactating) women Women of childbearing potential who do not agree to have a pregnancy test done at screening and who do not agree to use highly effective contraception while taking the investigational drug and for 5 days after stopping the investigational drug Sexually active males unwilling to use a condom during intercourse while taking the investigational drug and for 5 days after stopping the investigational drug Patients who cannot comply with the planned scheduled visits and procedures of the study protocol