Clinical trial NCT05593666: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Primary Visceral Leishmaniasis
Lead sponsor: Drugs for Neglected Diseases
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2022-10-25
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Proportion of patients with initial cure at Day 28 for LXE408
timeFrame: Day 28
Secondary outcomes:
measure: Proportion of patients with initial cure at Day 28 for AmBisome®
timeFrame: Day 28
measure: Proportion of patients with definitive cure at Day 180 for LXE408 and AmBisome®
timeFrame: Day 180
measure: Mortality
timeFrame: Days 28 and 180
measure: Cmax for LXE408
timeFrame: Days 1 and 7
measure: Tmax for LXE408
timeFrame: Days 1 and 7
measure: AUCtau for LXE408
timeFrame: Days 1 and 7
measure: CLss/F for LXE408
timeFrame: Days 1 and 7
measure: Cmax for Amphotericin B
timeFrame: Days 1 and 7
measure: AUC0-24h for Amphotericin B
timeFrame: Day 1
measure: AUC0-infinity for Amphotericin B
timeFrame: Day 1
measure: Blood parasite clearance
timeFrame: Baseline and Days 1, 3, 5, 7, 10, 14, 28 and 56
measure: Proportion of patients with a positive loop-mediated isothermal amplification (LAMP) from blood samples
timeFrame: Baseline and Days 28 and 56
measure: Tissue parasite loads
timeFrame: Baseline and Day 28
measure: Proportion of patients with a positive loop-mediated isothermal amplification (LAMP) from tissue samples
timeFrame: Baseline and Day 28
Other outcomes:
Locations:
city: Bihar
country: India
facility: DrugsNeglectedD Investigational Site
city: Patna
country: India
facility: DrugsNeglectedD Investigational Site
Study officials:
References: