Health Condition 1: B550- Visceral leishmaniasis
Conditions
Interventions
Intervention1: LXE408: Arm-1: 300 mg tablet Peroral (PO) once daily (QD) for 7 days, followed by once daily (QD) Matching Placebo for 7 Days. Matching Placebo has been added to keep the study blinded
Sponsors
Drugs for Neglected Diseases Initiative DNDi
Qascent Research Solutions Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1. 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 2. Patients for whom written informed consent has been obtained (if aged 18 years and over) or signed by the 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 3. Primary symptomatic VL (defined as typical parameters including, but not limited to, fever for > 2 weeks, weight loss, and splenomegaly) 4. Visualization of Leishmania amastigotes by microscopy in tissue samples (spleen or bone marrow)
Exclusion criteria
Exclusion criteria: 1. Clinical signs of severe VL (jaundice, spontaneous bleeding, edema, ascites, coma, organ failure). 2. 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 3. Patients with history of previous leishmaniasis and confirmed relapse. 4. Patients with para-kala-azar dermal leishmaniasis. 5. Patients with severe malnutrition (for children =12- 6. History of congenital or acquired immunodeficiency, including positive HIV (test at screening). 7. Known hypersensitivity to amphotericin B deoxycholate or any other constituents of AmBisome?. 8. 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). 9. 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. 10. Pregnant or nursing (lactating) women. 11. 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. 12. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of patients with initial cureTimepoint: At Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Frequency and severity of treatment-emergent adverse events (TEAEs), SAEs, and AEs requiring treatment discontinuation. Timepoint: Day 1 and up to and including Day 14;Descriptive statistics and frequency of physical exam abnormalities, vital signs, ECG abnormalities, safety laboratory assessments including clinical chemistry, hematology and urinalysis results.Timepoint: Up to and including end-of-study (EOS) Visit i.e. Day 180;All-cause mortality and mortality not associated with VLTimepoint: Days 28 and 180;PK Parameters (Cmax, Tmax, AUCtau, CLss/F) for LXE408Timepoint: Day 1 and Day 7;PK Parameters (Cmax, AUC0-24h, and AUC0-Infinity) for AmBisome Timepoint: Day 1;For Ambisome?: proportion of patients with initial cureTimepoint: Day 28;For LXE408 and Ambisome: proportion of patients with definitive cureTimepoint: Day 180;Blood parasite clearance over time, as measured by quantitative polymerase chain reaction (qPCR) from blood samplesTimepoint: Day 1, Day 3, Day 5, Day 7, Day 10, Day 14, Day 28, Day 56 and at any suspicion of relapse during the trial;Proportion of patients with a positive loop-mediated isothermal amplification (LAMP) from blood samplesTimepoint: Baseline, Day 28, Day 56, and at any suspicion of relapse during the trial;Tissue parasite loads, as measured by qPCR from tissue samples (spleen or bone marrow)Timepoint: Baseline, Day 28 and at any suspicion of relapse during the trial ;Proportion of patients with a positive LAMP from tissue samplesTimepoint: Baseline, Day 28, and at any suspicion of relapse;Exploratory Endpoint: Descriptive statistics of efficacy, safety, and PK parameters for adolescent patients included in LXE408 armsTimepoint: Up to and including end-of-study (EOS) Visit i.e. Day 180;Exploratory Endpoint: Host biomarkers: differentially expressed genes and pathways in peripheral blood by study drug, treatment outcomes, and drug related (S)AEs.Timepoint: Day 3, Day 7, Day 14, Day 28, Day 56, and at relapse, compared to basel | — |
Countries
India
Contacts
Public ContactDr Kavita Singh
Drugs for Neglected Diseases Initiative (DNDi)
Outcome results
None listed