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

NCT ID: NCT05593666

Last Updated: 2025-12-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-27
• Study Completion Date: 2025-12-30

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.

Detailed Description

This study is run by DNDi with Novartis as co-development partner

Conditions

Primary Visceral Leishmaniasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

LXE408 short regimen

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

Group Type: EXPERIMENTAL

LXE408

Intervention Type: DRUG

Film-coated tablets

Placebo

Intervention Type: OTHER

Placebo film-coated tablets

LXE408 long regimen

LXE408 once daily for 14 days

Group Type: EXPERIMENTAL

LXE408

Intervention Type: DRUG

Film-coated tablets

Standard of care

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

Group Type: ACTIVE_COMPARATOR

AmBisome®

Intervention Type: DRUG

Sterile lyophilised powder in a 15 mL sterile clear glass vial

Interventions

LXE408

Film-coated tablets

Intervention Type: DRUG

Placebo

Placebo film-coated tablets

Intervention Type: OTHER

AmBisome®

Sterile lyophilised powder in a 15 mL sterile clear glass vial

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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)

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 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Drugs for Neglected Diseases

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

DrugsNeglectedD Investigational Site

Bihār, , India

DrugsNeglectedD Investigational Site

Patna, , India

Countries

India

Other Identifiers

CLXE408A12201R

Identifier Type: OTHER

Identifier Source: secondary_id

DNDi-LXE408-01-VL

Identifier Type: -

Identifier Source: org_study_id