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

NCT05957978 | Completed Phase 2

• 2 other identifiers: DNDi-LXE408-02-VLCLXE408A12202R
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Primary Visceral Leishmaniasis

Outcome Measures

Primary Outcomes (1)

• Proportion of patients treated with LXE408 with initial cure at Day 28

  Initial cure is defined as clinical improvement of Visceral Leishmaniasis (VL), absence of parasites in the spleen or bone marrow (microscopy) and no rescue therapy up to and including Day 28.

  Day 28

Secondary Outcomes (9)

• Mortality

  Days 28 and 180

• Cmax for LXE408

  Days 1 and 13

• CLss/F for LXE408

  Days 1 and 13

• AUCtau for LXE408

  Days 1 and 13

• Tmax for LXE408

  Days 1 and 13

Study Arms (2)

LXE408

EXPERIMENTAL

LXE408 orally once daily for 14 days

Drug: LXE408

Standard of care

ACTIVE COMPARATOR

Standard of care sodium stibogluconate 20 mg/kg/day intravenous/intramuscular (IV/IM) q.d. and paromomycin 15 mg/kg/day IM q.d. for 17 days

Drug: sodium stibogluconate; Drug: Paromomycin

Interventions

LXE408 DRUG

Film-coated tablets

LXE408

sodium stibogluconate DRUG

Dosage/Administration: sodium stibogluconate 20 mg/kg/day intravenous/intramuscular (IV/IM) q.d.

Standard of care

Paromomycin DRUG

Dosage/Administration: paromomycin 15 mg/kg/day IM q.d.

Standard of care

Eligibility Criteria

• Age: 18 Years - 44 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

University of Gondar

Gonder, Ethiopia

Location

MeSH Terms

Interventions

LXE408; Antimony Sodium Gluconate; Paromomycin

Intervention Hierarchy (Ancestors)

Organic Chemicals; Gluconates; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates; Aminoglycosides; Glycosides

Study Officials

• Mezgebu Silamsaw, Dr

  University of Gondar, Ethiopia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2023
• First Posted: July 24, 2023
• Study Start: March 29, 2024
• Primary Completion: June 27, 2025
• Study Completion: November 13, 2025
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

ET (1)