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

Primary Visceral Leishmaniasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05593666
• Other study ID #: DNDi-LXE408-01-VL
• Secondary ID: CLXE408A12201R
• Status: Recruiting
• Phase: Phase 2
• Start date: December 27, 2022
• Est. completion date: January 2, 2025

Study information

• Verified date: February 2024
• Source: Drugs for Neglected Diseases
• Contact: Gwen Carn
• Phone: +41 79 799 3886
• Email: gcarn[@]dndi.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 105
• Est. completion date: January 2, 2025
• Est. primary completion date: January 2, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leishmaniasis
• Leishmaniasis, Visceral
• Primary Visceral Leishmaniasis

Intervention

Drug:
• LXE408
Film-coated tablets

Other:
• Placebo
Placebo film-coated tablets

Drug:
• AmBisome®
Sterile lyophilised powder in a 15 mL sterile clear glass vial

Locations

Country	Name	City	State
India	DrugsNeglectedD Investigational Site	Bihar
India	DrugsNeglectedD Investigational Site	Patna

Sponsors (2)

Lead Sponsor	Collaborator
Drugs for Neglected Diseases	Novartis Pharmaceuticals

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Proportion of patients with initial cure at Day 28 for AmBisome®	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	Proportion of patients with definitive cure at Day 180 for LXE408 and AmBisome®	Definitive cure described as initial cure at Day 28, no requirement for rescue treatment throughout the study, no death associated to VL and absence of any clinical parameters of VL at Day 180.	Day 180
Secondary	Mortality	All-cause mortality and mortality not associated with Visceral leishmaniasis (VL)	Days 28 and 180
Secondary	Cmax for LXE408	Maximum Observed Blood-drug Concentrations for LXE408	Days 1 and 7
Secondary	Tmax for LXE408	Time to Reach Maximum Blood-drug Concentrations for LXE408	Days 1 and 7
Secondary	AUCtau for LXE408	Area Under The Plasma Concentration-time Curve Over A Dosing Interval for LXE408	Days 1 and 7
Secondary	CLss/F for LXE408	Apparent Clearance for LXE408	Days 1 and 7
Secondary	Cmax for Amphotericin B	Maximum Observed Blood-drug Concentrations for Amphotericin B	Days 1 and 7
Secondary	AUC0-24h for Amphotericin B	Area under the plasma concentration-time curve from time zero to 24h for Amphotericin B	Day 1
Secondary	AUC0-infinity for Amphotericin B	Area under the plasma concentration-time curve from time zero to infinity for Amphotericin B	Day 1
Secondary	Blood parasite clearance	Blood parasite clearance over time, as measured by quantitative polymerase chain reaction (qPCR) from blood samples at defined time points and at any suspicion of relapse during the trial.	Baseline and Days 1, 3, 5, 7, 10, 14, 28 and 56
Secondary	Proportion of patients with a positive loop-mediated isothermal amplification (LAMP) from blood samples	Proportion of patients with a positive loop-mediated isothermal amplification (LAMP) from blood samples at defined time points and at any suspicion of relapse during the trial.	Baseline and Days 28 and 56
Secondary	Tissue parasite loads	Tissue parasite loads, as measured by qPCR from tissue samples (spleen or bone marrow) collected at defined time points and at any suspicion of relapse during the trial.	Baseline and Day 28
Secondary	Proportion of patients with a positive loop-mediated isothermal amplification (LAMP) from tissue samples	Proportion of patients with a positive loop-mediated isothermal amplification (LAMP) from tissue samples at defined time points and at any suspicion of relapse during the trial.	Baseline and Day 28