A Phase II, Multicentre, Randomized, Two-arm Blinded Study to Assess the Efficacy and Safety of Two LXE408 Regimens for Treatment of Patients With Primary Visceral Leishmaniasis

Inclusion Criteria:

• Male and female patients ≥ 18 years (at the time of the screening visit) who are ableto comply with the study protocol. Following a favourable interim analysis result,patients ≥12 <18 years will also be enrolled in the trial
• Patients for whom written informed consent has been obtained (if aged 18 years andover) or signed by parent(s) or legal guardian for patients under 18 years of age. Inthe case of minors, assent from the child 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 orbone marrow)

Exclusion Criteria:

• Clinical signs of severe VL (jaundice, spontaneous bleeding, edema, ascites, coma,organ failure)
• Laboratory abnormalities including ALT/SGPT > 3 times ULN, total bilirubin > 1.5 timesULN, creatinine >1.5 times ULN, amylase or lipase > 1.5 times ULN, haemoglobin < 6g/dL or other clinically significant abnormal laboratory parameters which, in theopinion of the investigator, may indicate severe VL
• Patients with history of previous leishmaniasis and confirmed relapse
• Patients with para-kala-azar dermal leishmaniasis
• Patients with severe malnutrition (for children ≥12-<18 years: BMI-for-age WHOreference curves by sex, z score < -3; for adults ≥18 years: BMI < 16)
• History of congenital or acquired immunodeficiency, including positive HIV (test atscreening)
• Known hypersensitivity to amphotericin B deoxycholate or any other constituents ofAmBisome®
• Concomitant infections such as tuberculosis, severe malaria, or any other seriousunderlying disease that may interfere with the disease assessment (e.g., cardiac,renal, hepatic, haematologic, and pancreatic)
• Infection with hepatitis B (HBV) or hepatitis C virus (HCV). A positive HBV surfaceantigen (HBsAg) test, or if standard local practice, a positive HBV core antigen test,excludes a subject. Patients with a positive HCV antibody test should have HCV RNAlevels measured. Patients with positive (detectable) HCV RNA should be excluded.
• Pregnant or nursing (lactating) women
• Women of childbearing potential who do not accept to have a pregnancy test done atscreening and/or who do not agree to use highly effective contraception while takingthe investigational drug and for 5 half-lives or 5 days, whichever is longer, afterstopping the investigational drug.
• Sexually active males unwilling to use a condom during intercourse while taking theinvestigational drug and for 5 half-lives or 5 days, whichever is longer, afterstopping the investigational drug.