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

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 (Mid-Upper Arm Circumference (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:
• •1. Clinically significant cardiac arrhythmias (e.g., sustained ventricular tachycardia and clinically significant second- or third-degree AV block without a pacemaker)
• •2. QTcF ≥ 450 ms
• •3. History of familial long QT syndrome or known family history of Torsades de Pointes
• •4. 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