A Randomized, Open-label, Phase II, Single-centre Study to Evaluate the Efficacy, Safety and Pharmacokinetics of LXE408 in Patients With Primary Visceral Leishmaniasis in Ethiopia

DNDi-LXE408-02-VL

This is a randomized, open-label, phase II, single-centre study, with one LXE408 regimen and one calibrator arm with the standard of care SSG combined with PM, to be conducted in male and female adult (≥18 years and \<45 years) patients with confirmed primary visceral leishmaniasis in Ethiopia.

2024-04-03

2025-06-30

2025-10-03

Recruiting

Early phase I

52

Inclusion Criteria: * Male and female patients ≥18 and \<45 years (at the time of the screening visit) who are able to comply with the study protocol * Written informed consent must be obtained before any study protocol specific assessment is performed, other than procedures performed as part of standard of care * 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 (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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 52, 'type': 'ESTIMATED'}}

2024-04-08