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ClinicalTrials.gov ID

NCT07463040

Lead Sponsor

Institute of Tropical Medicine, BelgiumOTHER

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Phase 3

Enrollment

900Estimated

Last Update Posted

Mar 10, 2026Actual

Start Date

Jan 1, 2027Estimated

Primary Completion Date

Mar 1, 2029Estimated

Completion Date

Aug 31, 2029Estimated

Official Title

A Multi-Arm, Multi-Stage Randomized Controlled Clinical Trial Evaluating Systemic Therapeutic Regimens for the Treatment of Cutaneous Leishmaniasis in Ethiopia

Brief Summary

MAMS4CL comprises a clinical trial with three embedded sub-studies designed to comprehensively evaluate the administered treatments and assess the impact of CL treatment on patients and the healthcare system.

The multi-centre multi-arm multi-stage phase 3 clinical trial is designed to rigorously evaluate a total of 4 alternative treatment options for systemic CL against Sodium Stibugluconate (SSG) as the standard of care. The trial comprises two seamlessly linked stages. In stage 1, all four investigational arms will be evaluated against the control arm for efficacy to inform the selection of the arms, based on a pre-defined efficacy threshold that will advance to stage 2, in addition to the control arm. After stage 2, the experimental interventions will be compared with SSG similar to a standard superiority trial for efficacy. The general study design in stage 1 and stage 2 will be identical; only the number of investigational arms may differ.

Patients will be randomized into the respective treatment arms at the recruitment sites of Arba Minch hospital, Boru Meda hospital and ALERT hospital in Ethiopia. Individuals will be hospitalized during the entire course of their treatment. As different arms have different treatment duration, patient hospitalization period and visit schedules will differ between arms. In total, the study will last 180 days for each participant.

• Cutaneous Leihmaniasis

• Sodium Stibogluconate (SSG)
• Miltefosine
• Miltefosine + Paromomycin
• Liposomal Amphotericin B (LAmB)
• Pentamidine isethionate

Ages Eligible for Study

Child (0-17)Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria:

• Parasitological (microscopy, culture or PCR) confirmation of leishmaniasis
• Age ≥4 and ≤65 years old
• Need systemic treatment based on meeting at least one of the following criteria: >4 lesions/ At least one with lesion size >4cm/ Mucosal involvement, or at risk for mucosal involvement (<1 cm from the nose, eyes or vermillion border of the lips)/ Previous failure of lesion-directed treatment /Lesions on areas not suitable for lesion-directed therapy (e.g. joints, eyelids, fingers)/ Deep or extensive lesion(s) with risk of functional impairment
• Informed consent provided, as follows: For patients ≥18 years of age: Patient is willing and able to provide informed consent. / For patients aged 8 to 17 years (inclusive): Parent or caregiver is willing and able to provide informed consent, and patient is willing and able to provide assent / For patients aged 4 to 7 years (inclusive): Parent or caregiver is willing and able to provide informed consent.
• Willing and able to be hospitalized for the duration of treatment
• Willing and able to attend all follow-up visits
• If female and of child-bearing age: willing to take contraceptives during treatment and for 5 months after EoT (parenteral, intrauterine device (IUD) or implant). Note that actually taking the contraceptives is only required when randomized in an investigational arm containing miltefosine.

Exclusion Criteria:

• Pregnant (positive pregnancy test at screening) or breastfeeding
• Any known severe medical comorbidities, or signs and symptoms of severe disease, that in the opinion of the investigator disqualifies the patient of being enrolled in the trial or precludes evaluation of the patient's response to the study medication. Examples are: Severe known active infections such as tuberculosis, schistosomiasis, malaria, hepatitis B virus, active hepatitis C virus/ Serious underlying disease (e.g. cardiac, renal, hepatic (including diabetes mellitus) or chronic disease/ Immunocompromising conditions: transplant patients, or patients receiving immunosuppressant medication/ Pre-existing ocular conditions evaluated at baseline: e.g. keratitis, uveitis, scleritis/ Pre-existing sensorineural hearing loss evaluated at baseline, or previously diagnosed with ototoxicity
• HIV Infection
• Severe malnutrition: ≤5 years old: Mean upper arm circumference (MUAC) <115mm/ 6-10 years old: MUAC <135mm/ 11-17 years old: MUAC <160mm/ ≥ 18 years old: Body mass index (BMI) <16kg/m²
• (History of) ECG abnormalities: Clinically significant cardiac arrythmias: e.g. 2nd degree or 3rd degree AV block without pacemaker, sustained ventricular tachycardia/ Prolonged QTc interval >450ms
• Lab abnormalities: Haemoglobin <5.0g/dL/ Platelets <50 x 10^9/L/ White blood count <1 x 10^9/L / Alanine aminotransferase (AST) / aspartate aminotransferase (ALT) >3x upper limit of normal (ULN)/ Serum creatinine >1.5 x ULN/ Bilirubin >1.5 x ULN/ Fasting blood glucose (preferred) >7mmol/L (126mg/dl) or blood glucose >11.1 mmol/L (200mg/dl) at any time/ Potassium <3.5mmol/L
• Having received any allopathic treatment for CL lesion(s) in the past 6 months: cryotherapy, thermotherapy, SSG, meglumine antimoniate, paromomycin, pentamidine, liposomal amphotericin B, non-liposomal amphotericin B, miltefosine
• Diffuse cutaneous leishmaniasis (DCL)
• Patients on treatment with any of the prohibited medications, which are any treatments with the potential to influence lesion healing, skin condition, or participant safety. This includes any form of chemotherapy, antituberculosis medication, systemic antibiotics or antifungals, antivirals, corticosteroids and immunosuppressants. Topical antibiotics or antifungals are allowed as long as they are not applied on any of the CL lesions.
• Onset of lesions >24 months ago
• Known allergies or serious adverse reactions to one of the study components/medications
• Any other condition for which participation in the trial, as judged by the investigator, could compromise the well-being of the patient or prevent, limit or confound protocol-specified assessments

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

Single

Lead Sponsor

Institute of Tropical Medicine, BelgiumOTHER

Collaborators

London School of Hygiene and Tropical MedicineOTHER

Uppsala UniversityOTHER

University of StellenboschOTHER

Armauer Hansen Research Institute, EthiopiaOTHER

Wollo UniversityOTHER

Arba Minch UniversityOTHER

mehrettechane@gmail.com

markwesaketema@gmail.com