Localized Cutaneous LeishmaniasisPhase 2NCT06997159
A Clinical Trial to Investigate Efficacy, Safety and Pharmacokinetics (PK) of Two LXE408 Oral Regimens and Oral Miltefosine as Active Control in Participants Aged ≥ 18 Years Old With Localized Cutaneous Leishmaniasis in the Region of the Americas (AMR).
A Phase 2 study testing LXE408 and Miltefosine 50 MG Oral Capsule [Impavido] in people with Localized Cutaneous Leishmaniasis, run by Drugs for Neglected Diseases at 5 sites in 2 countries.
Trial summary
The purpose of this clinical trial is to measure efficacy, safety and pharmacokinetics (PK) of two LXE408 oral regimens and oral miltefosine tablets as active control in localized cutaneous leishmaniasis in the region of the Americas (AMR), and assess its suitability for use in monotherapy for the treatment of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Localized Cutaneous Leishmaniasis
- What is being tested?
- LXE408 and Miltefosine 50 MG Oral Capsule [Impavido]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 250 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 15 Jun 2026to 5 Apr 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant must be aged ≥18 years old and weighing > 50kg
- Participant with first episode of CL fulfilling the following characteristics:
- ≤ 6 lesions
- At least one lesion of > 50 mm2 of area
- a history of CL of no longer than 6 months
- a diagnosis of CL confirmed by at least one of the following methods:
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- microscopic identification of amastigotes in stained lesion tissue, or
- demonstration of Leishmania by PCR, or
- positive culture for promastigotes
- In the opinion of the investigator, the participant is capable of understanding and complying with the protocol, including visits up to 6 months after study start.
- Written informed consent must be obtained before any study protocol specific assessment is performed other than procedures performed as part of standard of care.
- Participants must be able to give written informed consent.
Who cannot join
- Female with a positive blood pregnancy test at screening or who is breastfeeding, lactating or women of childbearing potential (defined as women physiologically capable of becoming pregnant) who does not agree to use two methods of contraception, one barrier method and one highly effective method. In Brazil: for 30 days prior to the treatment onset and up to D180 visit. In Panama: during treatment period up to D180 visit.
- Sexually active male, including those post-vasectomy, unwilling to use a condom during intercourse with female partner while taking the investigational drug and for 5 days, after stopping the investigational drug.
- Has diagnosis or suspected diagnosis of mucocutaneous, disseminated or diffuse leishmaniasis based on physical exam.
- Current clinically significant medical problems (e.g., cardiac, renal, hepatic, pancreatic diseases, current cutaneous conditions that may interfere with CL evolution or healing, past and current ocular disorders, especially keratitis, uveitis, scleritis), including any immunocompromising condition (such as having a known diagnosis for HIV, transplanted patients, those in treatment for auto immune diseases, patients receiving immunosuppressant, immunobiological or antineoplastic treatments).
- History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed).
- Participants newly diagnosed with HIV infection on the basis of the trial screening testing or other recent testing (< 6 months) are excluded. Participants with documented stable HIV infection are allowed to participate in the study. Stable HIV infection is defined as: clinically stable with no signs or symptoms of advanced HIV infection and taking their current anti-retroviral therapy for ≥ 6 months with an undetectable viral load for ≥ 6 months. Participants taking anti-retroviral therapy prohibited in Section 6.9.4 are excluded.
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- Participants with active infectious conditions, such as tuberculosis, or history or active hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection are excluded. Active HBV is defined as a positive HBV surface antigen (HBsAg) test, or if standard local practice, a positive HBV core antigen test and all participants with a positive HBV core antibody screening test must have HBsAg measured. Active HCV is defined as having detectable HCV RNA and all participants with a positive HCV antibody test at screening must have HCV RNA measured. Participants taking therapy for HBV or HCV are excluded.
- 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.
- Participants who are receiving or have received antileishmanial medication, or prohibited medication or any medication that might interfere with the therapeutic response or cause harmful interactions with study medications, as defined in concomitant treatments in Section 6.9.4.
- Has laboratory values at screening as follows:
- Serum creatinine: ≥1.5 times ULN, ALT, AST, GGT, ALP: >1.5 times above upper normal level. Total bilirubin > 1.5 times ULN amylase or lipase > 1.5 times ULN
- Normal ranges obtained from local laboratory.
- Known history of addiction/ alcohol abuse.
- Hypersensitivity to miltefosine or any study medication excipients.
- Participants with Sjogren-Larsson Syndrome.
Trial locations and contacts
5 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
5 sites in 2 countries
Brazil4 sites
René Rachou Institute /Oswaldo Cruz Foundation- FIOCRUZ MINAS
Belo Horizonte, Minas Gerais
Lorenza Campos Nogueira Dezanet
Lorenza Campos Nogueira Dezanet
Julio Muller University Hospital/ Federal University of Mato Grosso
Cuiabá, Mato Grosso
Marcia Hueb
Marcia Hueb
Foundation of Tropical Medicine Dr. Heitor Vieira Dourado
Manaus, Amazonas
Jorge Augusto de Oliveira Guerra
Jorge Augusto de Oliveira Guerra
Federal University of Maranhão
São Luís, Maranhão
Conceição de Maria Pedrozo e Silva de Azevedo
Conceição de Maria Pedrozo e Silva de Azevedo
Panama1 site
Instituto Conmemorativo Gorgas de Estudios de la Salud
Panama City
Juan Miguel Pascale
Juan Miguel Pascale
About this study
Official title: A Randomized, Multicentre, Observer-blind Phase II Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of Two LXE408 Regimens and Miltefosine as an Active Control in Patients With Localized Cutaneous Leishmaniasis in the Region of the Americas (AMR).
The purpose of this clinical trial is to measure efficacy, safety and pharmacokinetics (PK) of two LXE408 oral regimens and oral miltefosine tablets as active control in localized cutaneous leishmaniasis in the region of the Americas (AMR), and assess its suitability for use in monotherapy for the treatment of patients with cutaneous leishmaniasis (CL).
Read the detailed description
Participants who met all inclusion criteria and none of the exclusion criteria will be randomized to the study will be allocated to one of three arms in a 2:2:1 ratio.
- Arm 1: LXE408 BID for 14 days followed by placebo BID for 14 days
- Arm 2: LXE408 BID for 28 days
- Arm 3: Miltefosine 50 mg PO TID for 28 days orally
Each arm will consist of a screening period of up to 15 days, a 28-day treatment period, and a follow-up period from Day 29 to Day 180. During the treatment period, all participants will return to the sites at Days 1, 8, 15, 22 and 29 (+/- 2 days). During the follow-up period they will return for the Day 63 (+/- 7 days), Day 90 (+/- 7 days) and Day 180 (+/- 14 days) visits. If at D90 participants present a re-epithelization of the ulcer(s) more or equal to 75% but less than 100%, they will be asked to return at D105 for a late responder assessment.
- Conditions
- Localized Cutaneous Leishmaniasis
- Being tested
- LXE408, Miltefosine 50 MG Oral Capsule [Impavido], Placebo to LXE408
- Keywords
- Localized Cutaneous Leishmaniasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LXE408Drug
LXE408 film-coated tablets.
Miltefosine 50 MG Oral Capsule [Impavido]Drug
Each capsule contains 50 mg miltefosine in an opaque, red, hard gelatin capsule. Capsules are supplied in packs of 56 capsules sealed in 8 aluminum blister stripes, each containing 7 capsules.
Placebo to LXE408Drug
Film-coated tablets.
| Study group | Role | What they receive |
|---|---|---|
| LXE408 BID for 14 days | Experimental | LXE408 BID for 14 days followed by placebo BID for 14 days. Receives: Drug: LXE408; Drug: Placebo to LXE408 |
| LXE408 BID for 28 days | Experimental | Not described Receives: Drug: LXE408 |
| Miltefosine 50 mg PO TID for 28 days | Active comparator | Not described Receives: Drug: Miltefosine 50 MG Oral Capsule [Impavido] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants who achieved Cure at Day 180
Cure at Day 180 (D180) is defined as:
- 100% re-epithelialization of ulcerated lesions (if any) or flattening and/or no signs of induration of non-ulcerated lesions (if any) up to and at D90 and,
- no relapse by D180, and
- no rescue therapy up to D180
- no death, regardless of cause, up to D180
Measured: 180 days
Secondary outcomes (7)
Proportion of participants with treatment-emergent adverse events (TEAEs) and SAEs
Measured: 180 days
Proportion of participants with • Abnormalities from physical exam, vital signs, ECGs and safety laboratory assessments
Measured: 180 days
Proportion of participants who achieved Cure at Day 90
Cure at Day 90 (D90) is defined as:
- 100% re-epithelization of ulcerated lesions (if any) or flattening and/or no signs of induration of non-ulcerated lesions (if any) at D90;
- no rescue therapy up to D90.
- No-death regardless of cause up to D90.
Measured: 90 days
Pharmacokinetics (PK) of LXE408 - Cmax
Maximum plasma concentration
Measured: Day 1, Day 8 and Day 15
Pharmacokinetics (PK) of LXE408 - Tmax
Time to maximum plasma concentration
Measured: Day 1, Day 8 and Day 15
Pharmacokinetics (PK) of LXE408 - AUCtau
Area under plasma concentration-time curve over dosing interval
Measured: Day 1, Day 8 and Day 15
Proportion of participants who achieved cure in different species of Leishmania for participants treated with LXE408 and miltefosine
Measured: Day 90, Day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2025
- Study start15 Jun 2026 (estimated)
- Primary completion5 Apr 2028 (estimated)
- Study completion5 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Localized Cutaneous 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Drugs for Neglected Diseases
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06997159
- Sponsor's protocol ID
- DNDi-LXE408-03-CL
- Other IDs
- CLXE408C12201R
- Status last verified
- Apr 2026
- First submitted
- 13 May 2025
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Multicentre, Observer-blind Phase II Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of Two LXE408 Regimens and Miltefosine as an Active Control in Patients With Localized Cutaneous Leishmaniasis in the Region of the Americas (AMR).
- ClinicalTrials.gov ID
- NCT06997159
- Acronym / sponsor ID
- DNDi-LXE408-03-CL
- Conditions
- Localized Cutaneous Leishmaniasis
- Keywords
- Localized Cutaneous Leishmaniasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Drugs for Neglected DiseasesUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 15 Jun 2026 (estimated)
- Primary completion
- 5 Apr 2028 (estimated)
- Study completion
- 5 Apr 2028 (estimated)
- First posted
- 30 May 2025 (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.
The purpose of this clinical trial is to measure efficacy, safety and pharmacokinetics (PK) of two LXE408 oral regimens and oral miltefosine tablets as active control in localized cutaneous leishmaniasis in the region of the Americas (AMR), and assess its suitability for use in monotherapy for the treatment of patients with cutaneous leishmaniasis (CL).
Detailed description
Participants who met all inclusion criteria and none of the exclusion criteria will be randomized to the study will be allocated to one of three arms in a 2:2:1 ratio.
- Arm 1: LXE408 BID for 14 days followed by placebo BID for 14 days
- Arm 2: LXE408 BID for 28 days
- Arm 3: Miltefosine 50 mg PO TID for 28 days orally
Each arm will consist of a screening period of up to 15 days, a 28-day treatment period, and a follow-up period from Day 29 to Day 180. During the treatment period, all participants will return to the sites at Days 1, 8, 15, 22 and 29 (+/- 2 days). During the follow-up period they will return for the Day 63 (+/- 7 days), Day 90 (+/- 7 days) and Day 180 (+/- 14 days) visits. If at D90 participants present a re-epithelization of the ulcer(s) more or equal to 75% but less than 100%, they will be asked to return at D105 for a late responder assessment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| LXE408 BID for 14 days | Experimental | Drug: LXE408, Drug: Placebo to LXE408LXE408 BID for 14 days followed by placebo BID for 14 days. |
| LXE408 BID for 28 days | Experimental | Drug: LXE408 |
| Miltefosine 50 mg PO TID for 28 days | Active comparator | Drug: Miltefosine 50 MG Oral Capsule [Impavido] |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Participant must be aged ≥18 years old and weighing > 50kg
- Participant with first episode of CL fulfilling the following characteristics:
- a diagnosis of CL confirmed by at least one of the following methods:
- In the opinion of the investigator, the participant is capable of understanding and complying with the protocol, including visits up to 6 months after study start.
- Written informed consent must be obtained before any study protocol specific assessment is performed other than procedures performed as part of standard of care.
Key exclusion criteria (19 listed)
- Female with a positive blood pregnancy test at screening or who is breastfeeding, lactating or women of childbearing potential (defined as women physiologically capable of becoming pregnant) who does not agree to use two methods of contraception, one barrier method and one highly effective method. In Brazil: for 30 days prior to the treatment onset and up to D180 visit. In Panama: during treatment period up to D180 visit.
- Sexually active male, including those post-vasectomy, unwilling to use a condom during intercourse with female partner while taking the investigational drug and for 5 days, after stopping the investigational drug.
- Has diagnosis or suspected diagnosis of mucocutaneous, disseminated or diffuse leishmaniasis based on physical exam.
- Current clinically significant medical problems (e.g., cardiac, renal, hepatic, pancreatic diseases, current cutaneous conditions that may interfere with CL evolution or healing, past and current ocular disorders, especially keratitis, uveitis, scleritis), including any immunocompromising condition (such as having a known diagnosis for HIV, transplanted patients, those in treatment for auto immune diseases, patients receiving immunosuppressant, immunobiological or antineoplastic treatments).
- History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed).
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 |
|---|---|---|
| LXE408LXE408 film-coated tablets. | Drug | LXE408 BID for 14 days, LXE408 BID for 28 days |
| Miltefosine 50 MG Oral Capsule [Impavido]Each capsule contains 50 mg miltefosine in an opaque, red, hard gelatin capsule. Capsules are supplied in packs of 56 capsules sealed in 8 aluminum blister stripes, each containing 7 capsules. | Drug | Miltefosine 50 mg PO TID for 28 days |
| Placebo to LXE408Film-coated tablets. | Drug | LXE408 BID for 14 days |
Primary outcome
Proportion of participants who achieved Cure at Day 180
Time frame: 180 days
Cure at Day 180 (D180) is defined as: * 100% re-epithelialization of ulcerated lesions (if any) or flattening and/or no signs of induration of non-ulcerated lesions (if any) up to and at D90 and, * no relapse by D180, and * no rescue therapy up to D180 * no death, regardless of cause, up to D180
7 secondary outcomes
Proportion of participants with treatment-emergent adverse events (TEAEs) and SAEs
Time frame: 180 days
Proportion of participants with • Abnormalities from physical exam, vital signs, ECGs and safety laboratory assessments
Time frame: 180 days
Proportion of participants who achieved Cure at Day 90
Time frame: 90 days
Pharmacokinetics (PK) of LXE408 - Cmax
Time frame: Day 1, Day 8 and Day 15
Pharmacokinetics (PK) of LXE408 - Tmax
Time frame: Day 1, Day 8 and Day 15
Pharmacokinetics (PK) of LXE408 - AUCtau
Time frame: Day 1, Day 8 and Day 15
Proportion of participants who achieved cure in different species of Leishmania for participants treated with LXE408 and miltefosine
Time frame: Day 90, Day 180
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LXE408 and Miltefosine 50 MG Oral Capsule [Impavido] in people with Localized Cutaneous Leishmaniasis, run by Drugs for Neglected Diseases at 5 sites in 2 countries.
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 12 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: opening soon, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Brazil, Panama. 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?
This study is still under way. Results are not available in the source record yet.
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 participants who achieved Cure at Day 180 (time frame: 180 days). 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 5 May 2026.