Primary Visceral LeishmaniasisPhase 2NCT05957978
LXE408 for Treatment of Visceral Leishmaniasis in Ethiopia, a Proof of Concept Study
A Phase 2 study testing LXE408, sodium stibogluconate and Paromomycin in people with Primary Visceral Leishmaniasis, run by Drugs for Neglected Diseases at 1 site in Ethiopia.
Trial summary
This is a randomized, open-label, phase II, single-centre study, with one LXE408 regimen and one calibrator arm with the standard of care SSG combined with PM, to be conducted in male and female adult (≥18 years and <45 years) patients with confirmed primary visceral leishmaniasis in Ethiopia. Read more about this study
- Who is it for?
- Ages 18 to 44 years
- Conditions the study is for
- Primary Visceral Leishmaniasis
- What is being tested?
- LXE408, sodium stibogluconate and Paromomycin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteEthiopia
- Study dates
- 29 Mar 2024to 13 Nov 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 44 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
This is a randomized, open-label, phase II, single-centre study, with one LXE408 regimen and one calibrator arm with the standard of care SSG combined with PM, to be conducted in male and female adult (≥18 years and <45 years) patients with confirmed primary visceral leishmaniasis in Ethiopia.
Read the 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.
- Conditions
- Primary Visceral Leishmaniasis
- Being tested
- LXE408, sodium stibogluconate, Paromomycin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LXE408Drug
Film-coated tablets
sodium stibogluconateDrug
Dosage/Administration: sodium stibogluconate 20 mg/kg/day intravenous/intramuscular (IV/IM) q.d.
ParomomycinDrug
Dosage/Administration: paromomycin 15 mg/kg/day IM q.d.
| Study group | Role | What they receive |
|---|---|---|
| LXE408 | Experimental | LXE408 orally once daily for 14 days Receives: Drug: LXE408 |
| Standard of care | Active comparator | 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 Receives: Drug: sodium stibogluconate; Drug: Paromomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients treated with LXE408 with initial cure at 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.
Measured: Day 28
Secondary outcomes (9)
Mortality
All-cause mortality and mortality not associated with Visceral leishmaniasis (VL)
Measured: Days 28 and 180
Cmax for LXE408
Maximum Observed Blood-drug Concentrations for LXE408
Measured: Days 1 and 13
CLss/F for LXE408
Apparent Clearance for LXE408
Measured: Days 1 and 13
AUCtau for LXE408
Area Under The Plasma Concentration-time Curve Over A Dosing Interval for LXE408
Measured: Days 1 and 13
Tmax for LXE408
Time to Reach Maximum Blood-drug Concentrations for LXE408
Measured: Days 1 and 13
Proportion of LXE408 and SSG/PM patients with definitive cure at Day 180
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
Measured: 180 Days
Proportion of patients treated with SSG/PM with initial cure at 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
Measured: Day 28
Proportion of patients with positive/negative qPCR
Quantitative polymerase chain reaction (qPCR) from blood samples
Measured: 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
Tissue parasite loads, as measured by qPCR from tissue samples (spleen or bonemarrow)
Measured: Baseline and Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2023
- Study start29 Mar 2024
- Primary completion27 Jun 2025
- Study completion13 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Visceral LeishmaniasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Mezgebu Silamsaw, Dr, Principal investigator, University of Gondar, Ethiopia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05957978
- Sponsor's protocol ID
- DNDi-LXE408-02-VL
- Other IDs
- CLXE408A12202R
- Status last verified
- Dec 2025
- First submitted
- 14 Jun 2023
- Last updated
- 18 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05957978
- Acronym / sponsor ID
- DNDi-LXE408-02-VL
- Conditions
- Primary Visceral Leishmaniasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 29 Mar 2024 (actual)
- Primary completion
- 27 Jun 2025 (actual)
- Study completion
- 13 Nov 2025 (actual)
- First posted
- 24 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, open-label, phase II, single-centre study, with one LXE408 regimen and one calibrator arm with the standard of care SSG combined with PM, to be conducted in male and female adult (≥18 years and <45 years) patients with confirmed primary visceral leishmaniasis in Ethiopia.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LXE408 | Experimental | Drug: LXE408LXE408 orally once daily for 14 days |
| Standard of care | Active comparator | Drug: sodium stibogluconate, Drug: ParomomycinStandard 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 |
Who may qualify
- Ages
- 18 to 44 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (19 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LXE408Film-coated tablets | Drug | LXE408 |
| sodium stibogluconateDosage/Administration: sodium stibogluconate 20 mg/kg/day intravenous/intramuscular (IV/IM) q.d. | Drug | Standard of care |
| ParomomycinDosage/Administration: paromomycin 15 mg/kg/day IM q.d. | Drug | Standard of care |
Primary outcome
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.
9 secondary outcomes
Mortality
Time frame: Days 28 and 180
Cmax for LXE408
Time frame: Days 1 and 13
CLss/F for LXE408
Time frame: Days 1 and 13
AUCtau for LXE408
Time frame: Days 1 and 13
Tmax for LXE408
Time frame: Days 1 and 13
Proportion of LXE408 and SSG/PM patients with definitive cure at Day 180
Time frame: 180 Days
Proportion of patients treated with SSG/PM with initial cure at Day 28
Time frame: 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
Tissue parasite loads in LXE408 and SSG/PM patients
Time frame: Baseline and Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2025.
- Individual participant dataSharing planned: Yes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mezgebu Silamsaw, Dr principal investigator
University of Gondar, Ethiopia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LXE408, sodium stibogluconate and Paromomycin in people with Primary Visceral Leishmaniasis, run by Drugs for Neglected Diseases at 1 site in Ethiopia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ethiopia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients treated with LXE408 with initial cure at Day 28 (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2025.