- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05957978
LXE408 for Treatment of Visceral Leishmaniasis in Ethiopia, a Proof of Concept Study
A Randomized, Open-label, Phase II, Single-centre Study to Evaluate the Efficacy, Safety and Pharmacokinetics of LXE408 in Patients With Primary Visceral Leishmaniasis in Ethiopia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The study will enrol and randomize approximately 52 patients aged ≥18 years and <45 years in a ratio of 3:1 (arm 1 to arm 2):
- Arm 1: LXE408 orally once daily for 14 days (39 patients)
- Arm 2: Standard of care sodium stibogluconate 20 mg/kg/day intravenous/intramuscular (IV/IM) q.d. and paromomycin 15 mg/kg/day IM q.d. for 17 days (13 patients)
In both arms, the study will consist of a screening period of up to 7 days, a treatment duration of 14 or 17 days, and a follow-up period from end of treatment to Day 180. All patients will be hospitalized for approximately 21-24 days, from the first day of the screening period to the Day 14 or Day 17 visit (LXE408 or SSG/PM arms, respectively), after which they are expected to be discharged. They will return to the study sites at the scheduled Day 28 visit (±1 day) for the initial test of cure (primary endpoint), at Day 56 visit (± 7 days) and for the EOS visit at Day 180 (± 14 days) for the final assessment of cure (secondary endpoint). In addition, during follow-up between Day 56 and Day 180, the study team will contact the study patients by phone on a monthly basis to check on their well-being and any reappearance of VL symptoms.
This study is run by DNDi with Novartis as co-development partner.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Alexandra Solomos
- Phone Number: + 41 22 906 92 69
- Email: asolomos@dndi.org
Study Locations
-
-
-
Gondar, Ethiopia
- Recruiting
- University of Gondar
-
Contact:
- Mezgebu Silamsaw Asres, MD, DTMH
- Phone Number: +251921576259
- Email: msilamsaw@gmail.com
-
Contact:
- Eleni Ayele, MD
- Phone Number: +251910448652
- Email: eleniayele2@gmail.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male and female patients ≥18 and <45 years (at the time of the screening visit) who are able to comply with the study protocol
- Written informed consent must be obtained before any study protocol specific assessment is performed, other than procedures performed as part of standard of care
- 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 (including for example jaundice, spontaneous bleeding, oedema, ascites, coma, organ failure)
- Laboratory abnormalities including ALT/SGPT >3 times ULN, total bilirubin >1.5 times ULN, creatinine >1.5 times ULN, serum 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 visceral leishmaniasis and confirmed relapse
- Patients with para-kala-azar dermal leishmaniasis
- Patients with severe malnutrition (Mid-Upper Arm Circumference (MUAC) <170 mm)
- History of congenital or acquired immunodeficiency, including positive HIV (test at screening), as these patients present lower efficacy rates, higher toxicity and higher lethality compared to non-HIV patients, requiring different case management and care
ECG abnormalities, either historic (no longer present) or current which, in the view of the investigator, indicate a significant risk to study participation. These include, but are not limited to, the following:
- Clinically significant cardiac arrhythmias (e.g., sustained ventricular tachycardia and clinically significant second- or third-degree AV block without a pacemaker)
- QTcF ≥ 450 ms
- History of familial long QT syndrome or known family history of Torsades de Pointes
- Resting heart rate (physical exam or 12 lead ECG) <60 bpm
- Concomitant known infections, including tuberculosis, severe malaria and any other serious underlying disease that may interfere with disease assessment (e.g., cardiac, renal, hepatic, haematologic and pancreatic)
- Infection with hepatitis B (HBV) or hepatitis C virus (HCV). Patients with a positive HBV surface antigen (HBsAg) test, or if standard local practice, a positive HBV core antigen test, and patients with a positive HCV antibody test must be excluded and will be followed up as per local practice.
- Known history of hearing impairment and/or clinical signs and symptoms of hearing impairment identified during routine physical examination
- Patients with previous history of hypersensitivity reaction or known drug class allergy to any of the study treatments or excipients
- Pregnant or nursing (lactating) women
- Women of childbearing potential who do not agree to have a pregnancy test done at screening and who do not agree to use highly effective contraception while taking the investigational drug and for 5 days after stopping the investigational drug
- Sexually active males unwilling to use a condom during intercourse while taking the investigational drug and for 5 days after stopping the investigational drug
- Patients who cannot comply with the planned scheduled visits and procedures of the study protocol
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: LXE408
LXE408 orally once daily for 14 days
|
Film-coated tablets
|
Active Comparator: Standard of care
Standard of care sodium stibogluconate 20 mg/kg/day intravenous/intramuscular (IV/IM) q.d. and paromomycin 15 mg/kg/day IM q.d. for 17 days
|
Dosage/Administration: sodium stibogluconate 20 mg/kg/day intravenous/intramuscular (IV/IM) q.d.
Dosage/Administration: paromomycin 15 mg/kg/day IM q.d.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of patients treated with LXE408 with initial cure at Day 28
Time Frame: Day 28
|
Initial cure is defined as clinical improvement of Visceral Leishmaniasis (VL), absence of parasites in the spleen or bone marrow (microscopy) and no rescue therapy up to and including Day 28.
|
Day 28
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mortality
Time Frame: Days 28 and 180
|
All-cause mortality and mortality not associated with Visceral leishmaniasis (VL)
|
Days 28 and 180
|
Cmax for LXE408
Time Frame: Days 1 and 13
|
Maximum Observed Blood-drug Concentrations for LXE408
|
Days 1 and 13
|
CLss/F for LXE408
Time Frame: Days 1 and 13
|
Apparent Clearance for LXE408
|
Days 1 and 13
|
AUCtau for LXE408
Time Frame: Days 1 and 13
|
Area Under The Plasma Concentration-time Curve Over A Dosing Interval for LXE408
|
Days 1 and 13
|
Tmax for LXE408
Time Frame: Days 1 and 13
|
Time to Reach Maximum Blood-drug Concentrations for LXE408
|
Days 1 and 13
|
Proportion of LXE408 and SSG/PM patients with definitive cure at Day 180
Time Frame: 180 Days
|
Definitive cure at Day 180 is defined as initial cure at Day 28, no requirement for rescue treatment throughout the study, no death associated with VL and absence of any clinical parameters of VL up to and including Day180
|
180 Days
|
Proportion of patients treated with SSG/PM with initial cure at Day 28
Time Frame: Day 28
|
Initial cure is defined as clinical improvement of Visceral Leishmaniasis (VL), absence of parasites in the spleen or bone marrow (microscopy) and no rescue therapy up to and including Day 28
|
Day 28
|
Proportion of patients with positive/negative qPCR
Time Frame: Baseline and Days 1, 3, 5, 7, 10, 14, 28, 56, and relapse from Day 28 to Day 180. For patients included in the intensive PK sampling, Baseline and Days 1, 2, 3, 5, 7, 10, 14, 28, 56, and relapse from Day 28 to Day 180
|
Quantitative polymerase chain reaction (qPCR) from blood samples
|
Baseline and Days 1, 3, 5, 7, 10, 14, 28, 56, and relapse from Day 28 to Day 180. For patients included in the intensive PK sampling, Baseline and Days 1, 2, 3, 5, 7, 10, 14, 28, 56, and relapse from Day 28 to Day 180
|
Tissue parasite loads in LXE408 and SSG/PM patients
Time Frame: Baseline and Day 28
|
Tissue parasite loads, as measured by qPCR from tissue samples (spleen or bonemarrow)
|
Baseline and Day 28
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Mezgebu Silamsaw, Dr, University of Gondar, Ethiopia
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
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
- Anti-Bacterial Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Anthelmintics
- Schistosomicides
- Antiplatyhelmintic Agents
- Paromomycin
- Antimony Sodium Gluconate
Other Study ID Numbers
- DNDi-LXE408-02-VL
- CLXE408A12202R (Other Identifier: Novartis Pharmaceuticals)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
Clinical Trials on Primary Visceral Leishmaniasis
-
Drugs for Neglected DiseasesNovartis PharmaceuticalsRecruiting
-
Drugs for Neglected DiseasesGilead Sciences; Paladin Labs Inc.Completed
-
Drugs for Neglected DiseasesWellcome Trust grant 212346/Z/18/Z - 21st Century Treatments for Sustainable...CompletedVisceral Leishmaniasis | Cutaneous LeishmaniasesUnited Kingdom
-
Centre Hospitalier Universitaire de NiceCompleted
-
IDRIBill and Melinda Gates FoundationCompletedVisceral Leishmaniasis | Post-kala-azar Dermal LeishmaniasisIndia
-
Centre Hospitalier Universitaire de NiceRecruiting
-
International Centre for Diarrhoeal Disease Research...CompletedVisceral LeishmaniasisBangladesh
-
Aurobindo Pharma LtdAxis Clinicals LimitedCompletedVisceral LeishmaniasisBangladesh, India
-
Drugs for Neglected DiseasesCompletedVisceral LeishmaniasisUganda, Kenya
-
Banaras Hindu UniversityCompletedVisceral LeishmaniasisIndia
Clinical Trials on LXE408
-
Drugs for Neglected DiseasesNovartis PharmaceuticalsRecruiting