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

NCT05593666 | Completed Phase 2 DMC

• 2 other identifiers: DNDi-LXE408-01-VLCLXE408A12201R
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase II, multicentre, randomized, two-arm blinded study with an open label calibrator arm in adults and adolescents (≥12 years) with confirmed primary VL.

Conditions

Primary Visceral Leishmaniasis

Outcome Measures

Primary Outcomes (1)

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

  Initial cure defined as clinical improvement of Visceral leishmaniasis (VL), absence of parasites in the spleen or bone marrow (microscopy), and no rescue therapy on or before Day 28.

  Day 28

Secondary Outcomes (14)

• Proportion of patients with initial cure at Day 28 for AmBisome®

  Day 28

• Proportion of patients with definitive cure at Day 180 for LXE408 and AmBisome®

  Day 180

• Mortality

  Days 28 and 180

• Cmax for LXE408

  Days 1 and 7

• Tmax for LXE408

  Days 1 and 7

Study Arms (3)

LXE408 short regimen

EXPERIMENTAL

LXE408 once daily for seven days (followed by 7 days of placebo).

Drug: LXE408; Other: Placebo

LXE408 long regimen

EXPERIMENTAL

LXE408 once daily for 14 days

Drug: LXE408

Standard of care

ACTIVE COMPARATOR

AmBisome® 10 mg/kg IV single dose (SDA)

Drug: AmBisome®

Interventions

LXE408 DRUG

Film-coated tablets

LXE408 long regimen; LXE408 short regimen

Placebo OTHER

Placebo film-coated tablets

LXE408 short regimen

AmBisome® DRUG

Sterile lyophilised powder in a 15 mL sterile clear glass vial

Standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients ≥ 18 years (at the time of the screening visit) who are able to 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 and over) or signed by parent(s) or legal guardian for patients under 18 years of age. In the 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 or bone marrow)

You may not qualify if:

• 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 times ULN, creatinine \>1.5 times ULN, 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 previous leishmaniasis and confirmed relapse
• Patients with para-kala-azar dermal leishmaniasis
• Patients with severe malnutrition (for children ≥12-\<18 years: BMI-for-age WHO reference curves by sex, z score \< -3; for adults ≥18 years: BMI \< 16)
• History of congenital or acquired immunodeficiency, including positive HIV (test at screening)
• Known hypersensitivity to amphotericin B deoxycholate or any other constituents of AmBisome®
• Concomitant infections such as tuberculosis, severe malaria, or any other serious underlying 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 surface antigen (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 RNA levels 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 at screening and/or who do not agree to use highly effective contraception while taking the investigational drug and for 5 half-lives or 5 days, whichever is longer, after stopping the investigational drug.
• Sexually active males unwilling to use a condom during intercourse while taking the investigational drug and for 5 half-lives or 5 days, whichever is longer, after stopping the investigational drug.

Sponsors & Collaborators

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

Study Sites (2)

DrugsNeglectedD Investigational Site

Bihār, India

Location

DrugsNeglectedD Investigational Site

Patna, India

Location

MeSH Terms

Interventions

LXE408; liposomal amphotericin B

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2022
• First Posted: October 25, 2022
• Study Start: December 27, 2022
• Primary Completion: April 15, 2025
• Study Completion: December 22, 2025
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

IN (2)