- ICH GCP
- US Clinical Trials Registry
- 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
February 28, 2024 updated by: Drugs for Neglected Diseases
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
This study is run by DNDi with Novartis as co-development partner
Study Type
Interventional
Enrollment (Estimated)
105
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Gwen Carn
- Phone Number: +41 79 799 3886
- Email: gcarn@dndi.org
Study Locations
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-
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Bihar, India
- Recruiting
- DrugsNeglectedD Investigational Site
-
Patna, India
- Recruiting
- DrugsNeglectedD Investigational Site
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: LXE408 short regimen
LXE408 once daily for seven days (followed by 7 days of placebo).
|
Film-coated tablets
Placebo film-coated tablets
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Experimental: LXE408 long regimen
LXE408 once daily for 14 days
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Film-coated tablets
|
Active Comparator: Standard of care
AmBisome® 10 mg/kg IV single dose (SDA)
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Sterile lyophilised powder in a 15 mL sterile clear glass vial
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients with initial cure at Day 28 for LXE408
Time Frame: Day 28
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients with initial cure at Day 28 for AmBisome®
Time Frame: Day 28
|
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
|
Proportion of patients with definitive cure at Day 180 for LXE408 and AmBisome®
Time Frame: Day 180
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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
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Mortality
Time Frame: Days 28 and 180
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All-cause mortality and mortality not associated with Visceral leishmaniasis (VL)
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Days 28 and 180
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Cmax for LXE408
Time Frame: Days 1 and 7
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Maximum Observed Blood-drug Concentrations for LXE408
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Days 1 and 7
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Tmax for LXE408
Time Frame: Days 1 and 7
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Time to Reach Maximum Blood-drug Concentrations for LXE408
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Days 1 and 7
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AUCtau for LXE408
Time Frame: Days 1 and 7
|
Area Under The Plasma Concentration-time Curve Over A Dosing Interval for LXE408
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Days 1 and 7
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CLss/F for LXE408
Time Frame: Days 1 and 7
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Apparent Clearance for LXE408
|
Days 1 and 7
|
Cmax for Amphotericin B
Time Frame: Days 1 and 7
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Maximum Observed Blood-drug Concentrations for Amphotericin B
|
Days 1 and 7
|
AUC0-24h for Amphotericin B
Time Frame: Day 1
|
Area under the plasma concentration-time curve from time zero to 24h for Amphotericin B
|
Day 1
|
AUC0-infinity for Amphotericin B
Time Frame: Day 1
|
Area under the plasma concentration-time curve from time zero to infinity for Amphotericin B
|
Day 1
|
Blood parasite clearance
Time Frame: Baseline and Days 1, 3, 5, 7, 10, 14, 28 and 56
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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.
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Baseline and Days 1, 3, 5, 7, 10, 14, 28 and 56
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Proportion of patients with a positive loop-mediated isothermal amplification (LAMP) from blood samples
Time Frame: Baseline and Days 28 and 56
|
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
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Tissue parasite loads
Time Frame: Baseline and Day 28
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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
|
Proportion of patients with a positive loop-mediated isothermal amplification (LAMP) from tissue samples
Time Frame: Baseline and Day 28
|
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 27, 2022
Primary Completion (Estimated)
January 2, 2025
Study Completion (Estimated)
January 2, 2025
Study Registration Dates
First Submitted
October 20, 2022
First Submitted That Met QC Criteria
October 20, 2022
First Posted (Actual)
October 25, 2022
Study Record Updates
Last Update Posted (Estimated)
February 29, 2024
Last Update Submitted That Met QC Criteria
February 28, 2024
Last Verified
February 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Infections
- Vector Borne Diseases
- Parasitic Diseases
- Protozoan Infections
- Skin Diseases, Parasitic
- Skin Diseases, Infectious
- Euglenozoa Infections
- Leishmaniasis
- Leishmaniasis, Visceral
- Anti-Infective Agents
- Antifungal Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Liposomal amphotericin B
Other Study ID Numbers
- DNDi-LXE408-01-VL
- CLXE408A12201R (Other Identifier: Novartis Pharmaceuticals)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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