Study Comparing Several Drugs to Understand Which Work Against Cutaneous Leishmaniasis (CL)

NCT07463040 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: MAMS4CL
• Study Type: interventional
• Target: 900
• Locations: 1 country
• Sites: 3

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.

Conditions

Cutaneous Leihmaniasis

Keywords

Multi-Arm Multi-Stage; Standard of care; Sodium stibogluconate; Miltefosine; Paromomycin; Liposomal amphotericin B; Pentamidine; Ethiopia; cutaneous Leishmaniasis

Outcome Measures

Primary Outcomes (1)

• For each of the investigational arms (miltefosine/miltefosine + paromomycin / liposomal amphotericin B/pentamidine isethionate), to determine whether it has superior efficacy to the control arm in terms of achieving cure of all lesions at Day 90

  Cure of all lesions at Day 90, pairwise compared between the control arm and each of the investigational arms. Cure at the lesion level is defined as 100% improvement of the area of erythema, induration, and ulceration of a lesion compared to the baseline assessment. Cure at the patient level is defined as cure of all lesions present at baseline, and no new lesions appearing. Cure is assessed at multiple timepoints, including Day 90. Cure at Day 90 is defined as cure assessed at Day 90, or cure assessed at the latest available time point before Day 90, without relapse (known as last observation carried forward (LOCF)).

  Day 90

Secondary Outcomes (6)

• For each investigational arm, to determine whether it has superior efficacy to the control arm, in terms of achieving cure of all lesions at Day 180.

  Day 180

• To compare between the control arm and each of the investigational arms: proportion of participants with all lesions cured, cure for all lesions considered individually, the proportion of participants whose index lesion is cured.

  End of Treatment, Day 42, Day 90 and Day 180

• To compare between the control arm and each of the investigational arms: proportion of participants that reach at least substantial improvement of all lesions and the index lesion + at least substantial improvement for all lesions individually,

  End of Treatment, Day 42, Day 90, Day 180

• To compare between the control arm and each of the investigational arms, the proportion of participants with treatment failure at Day 42, Day 90, and Day 180.

  Day 42, Day 90, Day 180

• To assess safety by describing safety & tolerability of each arm by listing number, proportion & severity of AEs/Comparing number, proportion & reason of withdrawals and number & proportion of patients with SAEs between control and investigational arm

  Day 180

Other Outcomes (4)

• PK/PD outcome: To assess plasma and skin concentrations of SSG, miltefosine, paromomycin, LAmB, and pentamidine

  Day 14, Day 21 or Day 28 depending on treatment arm

• PK/PD outcome: To characterize the PK profiles of SSG, miltefosine, paromomycin, LAmB, and pentamidine

  from 24 hours post dose until Day 14, Day 21 or Day 28 depending treatment arm

• PK/PD outcome: To evaluate the correlation between PK parameters and clinical outcome within the control arm and each investigational arm.

  Day 90, Day 180

Study Arms (5)

Control arm

ACTIVE COMPARATOR

Standard of Care: Sodium Stibogluconate

Drug: Sodium Stibogluconate (SSG)

Miltefosine Arm

ACTIVE COMPARATOR

Miltefosine

Drug: Miltefosine

Miltefosine + Paromomycin Arm

ACTIVE COMPARATOR

Miltefosine + Paromomycin

Drug: Miltefosine + Paromomycin

LamB Arm

ACTIVE COMPARATOR

Liposomal amphotericin B

Drug: Liposomal Amphotericin B (LAmB)

Pentamidine Arm

ACTIVE COMPARATOR

Pentamidine isethionate

Drug: Pentamidine isethionate

Interventions

Sodium Stibogluconate (SSG) DRUG

Intramuscular Administration - once daily for 28 days

Control arm

Miltefosine DRUG

Miltefosine - Oral Administration, daily for 28 days

Miltefosine Arm

Miltefosine + Paromomycin DRUG

Miltefosine - Oral Administration, daily for 28 days + Paromomycine - Intramuscular Administration, once daily for 14 days

Miltefosine + Paromomycin Arm

Liposomal Amphotericin B (LAmB) DRUG

Intravenous Administration, once daily on days 1, 3, 5, 7, 10, 12, 14, 17, 19, 21

LamB Arm

Pentamidine isethionate DRUG

Intravenous Administration - once daily on days 1, 3, 5, 7, 9, 11, 13

Pentamidine Arm

Eligibility Criteria

• Age: 4 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• London School of Hygiene and Tropical Medicine: collaborator
• Uppsala University: collaborator
• University of Stellenbosch: collaborator
• Armauer Hansen Research Institute (AHRI), Ethiopia: collaborator
• Wollo University: collaborator
• Arba Minch University: collaborator

Study Sites (3)

ALERT Hospital

Addis Ababa, Ethiopia

Location

Arba Minch General Hospital

Arba Minch, Ethiopia

Location

Boru Meda General Hospital

Boru, Ethiopia

Location

MeSH Terms

Conditions

Leishmaniasis, Cutaneous

Interventions

Antimony Sodium Gluconate; miltefosine; Paromomycin; liposomal amphotericin B; Pentamidine

Condition Hierarchy (Ancestors)

Leishmaniasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Organic Chemicals; Gluconates; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates; Aminoglycosides; Glycosides; Benzamidines; Amidines

Study Officials

• Johan Van Griensven

  Institute of Tropical Medicine, Antwerp, Belgium

  STUDY DIRECTOR

Central Study Contacts

Bart Smekens

CONTACT

+3233455672; bsmekens@itg.be

Katrien Clinckx

CONTACT

kclinckx@itg.be

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-Arm Multi-stage

Study Record Dates

• First Submitted: February 9, 2026
• First Posted: March 10, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): August 31, 2029
• Last Updated: March 10, 2026

Record last verified: 2026-03

Locations

ET (3)