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).

NCT06997159 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: DNDi-LXE408-03-CLCLXE408C12201R
• Study Type: interventional
• Target: 250
• Locations: 2 countries
• Sites: 5

Brief 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 patients with cutaneous leishmaniasis (CL).

Conditions

Localized Cutaneous Leishmaniasis

Keywords

Localized Cutaneous Leishmaniasis

Outcome Measures

Primary Outcomes (1)

• 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

  180 days

Secondary Outcomes (7)

• Proportion of participants with treatment-emergent adverse events (TEAEs) and SAEs

  180 days

• Proportion of participants with • Abnormalities from physical exam, vital signs, ECGs and safety laboratory assessments

  180 days

• Proportion of participants who achieved Cure at Day 90

  90 days

• Pharmacokinetics (PK) of LXE408 - Cmax

  Day 1, Day 8 and Day 15

• Pharmacokinetics (PK) of LXE408 - Tmax

  Day 1, Day 8 and Day 15

Study Arms (3)

LXE408 BID for 14 days

EXPERIMENTAL

LXE408 BID for 14 days followed by placebo BID for 14 days.

Drug: LXE408; Drug: Placebo to LXE408

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]

Interventions

LXE408 DRUG

LXE408 film-coated tablets.

LXE408 BID for 14 days; LXE408 BID for 28 days

Placebo to LXE408 DRUG

Film-coated tablets.

LXE408 BID for 14 days

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.

Miltefosine 50 mg PO TID for 28 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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\*

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (5)

Foundation of Tropical Medicine Dr. Heitor Vieira Dourado

Manaus, Amazonas, Brazil

Location

Federal University of Maranhão

São Luís, Maranhão, Brazil

Location

Julio Muller University Hospital/ Federal University of Mato Grosso

Cuiabá, Mato Grosso, Brazil

Location

René Rachou Institute /Oswaldo Cruz Foundation- FIOCRUZ MINAS

Belo Horizonte, Minas Gerais, Brazil

Location

Instituto Conmemorativo Gorgas de Estudios de la Salud

Panama City, Panama

Location

MeSH Terms

Interventions

LXE408; miltefosine

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and investigators are partially blinded: they will be blinded for the two investigational LXE408 arms, which will reduce bias in the clinical assessment of safety and efficacy. However, both participants and investigators will be aware whether they are assigned to the investigational arms or to the miltefosine arm.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2025
• First Posted: May 30, 2025
• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): April 5, 2028
• Study Completion (Estimated): April 5, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

BR (4); PA (1)