Combination, Miltefosine Monotherapy for Cutaneous Leishmaniasis in New World

NCT04515186 | Completed Phase 3 DMC FDA Drug FDA Device

• 1 other identifier: DNDi-MILT-08-CL
• Study Type: interventional
• Target: 184
• Locations: 4 countries
• Sites: 6

Brief Summary

This study evaluates if the combination of thermotherapy (one application, 50⁰C for 30") and 3 weeks of miltefosine is safe and have a comparable cure rate with the current recommended first line treatments comprising meglumine antimoniate for 3 weeks for the treatment of uncomplicated cutaneous leishmaniasis cases in the New World.

Conditions

Cutaneous Leishmaniases

Outcome Measures

Primary Outcomes (1)

• The proportion of initial clinical cure in each arm.

  Defined for ulcerated lesions as 100% re-epithelialization of the ulcer(s) on D90 as compared to D1 and for non-ulcerated lesions as flattening and/or no signs of induration of the lesion(s) on D90 as compared to D1.

  Day 90

Secondary Outcomes (5)

• The number of patients who fulfil the criteria for clinical improvement at D90 and late responders at D105.

  Days 90 and 105

• The number of patients who fulfil the criteria of initial cure at D90 or late responders at D105 and have no relapse by D180 (final cure).

  Day 180

• Percentage of treatment discontinuation, frequency, severity, causality with each study drug and seriousness of AEs by treatment group.

  Through study completion, i.e up to 6 months

• Proportion of lesions with 100% re-epithelialization/flattening at each measurement time point by Leishmania sp.

  Days 7, 14 and 21. At end of treatment (days 21 or 28), and at days 45, 63, 90, 105 and 180.

• The number of patients randomized in the meglumine antimoniate arm until its discontinuation who fulfill the criteria of initial cure at D90 or late responders at D105 and have no relapse by D180 (final cure).

  Day 180

Study Arms (3)

Meglumine Antimoniate

OTHER

Meglumine Antimoniate, 20 mg/kg/day for 20 days parenterally. This trial arm was discontinued after protocol amendment 7. However, patients assigned to this arm before protocol amendment 7 becomes effective will continue in the study and will receive complete treatment as initially planned.

Drug: Meglumine Antimoniate

Miltefosine monotherapy

ACTIVE COMPARATOR

Miltefosine monotherapy 2.5 mg/kg/day for 28 days orally

Drug: Miltefosine

Thermotherapy + miltefosine

EXPERIMENTAL

Thermotherapy (one session, 50⁰C for 30" applications\*) + miltefosine 2.5 mg/kg/day for 21 days orally.

Drug: Miltefosine; Device: Thermotherapy machine

Interventions

Meglumine Antimoniate DRUG

Vials of a 5mL solution. Each vial contains 405 mg of Sb5+ corresponding to 8.1% Sb5+ (81 mg/mL).

Also known as: Glucantime®

Meglumine Antimoniate

Miltefosine DRUG

50 mg capsule

Also known as: Impavido®

Miltefosine monotherapy; Thermotherapy + miltefosine

Thermotherapy machine DEVICE

Localized Current Field radio-frequency generating device

Also known as: ThermoMed™

Thermotherapy + miltefosine

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Males and females, aged ≥12 and ≤60 years old (upper age limit according to local regulations), and weighing ≥ 30Kg.
• Patient with a confirmed diagnosis of CL in at least one lesion by at least one of the following methods: 1) microscopic identification of amastigotes in stained lesion tissue, or 2) demonstration of Leishmania by Polymerase Chain Reaction (PCR), or 3) positive culture for promastigotes.
• Patient has a lesion that satisfies the following criteria:
• Lesion size ≥ 0.5 cm and ≤ 4 cm (longest diameter).
• not located on the ear, face, close to mucosal membranes, or on a location that in the opinion of the Principal Investigator (PI) is difficult to apply the TT.
• Patient with ≤ 4 CL lesions.
• Duration of lesion less than 4 months by patient history.
• Patient able to give written informed consent/ assent form.
• In the opinion of the investigator, the patient is capable of understanding and complying with the protocol.

You may not qualify if:

• Female with a positive urine or blood pregnancy test at screening or who is breast feeding or female at fertile age who does not agree to take appropriate effective contraception during treatment period and up to D180 visit. In Brazil: female at fertile age who does not agree to use two effective methods of contraception: one barrier method and one highly effective method (defined in section 8.2.4) 30 days prior to the treatment onset and up to D180 visit.
• History of clinically significant medical problems / treatment that might interact, either negatively or positively, with treatment of cutaneous leishmaniasis including any immunocompromising condition.
• Within 8 weeks (56 days) of Day 1, received treatment for the entry lesion leishmaniasis with any medication including antimonials likely, in the opinion of the PI, to modify the course of the Leishmania infection.
• Has diagnosis or suspected diagnosis of mucocutaneous leishmaniasis based on physical exam.
• Has laboratory values at screening as follows:
• Serum creatinine: above upper normal level\*.
• Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST): 3 times above upper normal level\*.
• Normal ranges obtained from local laboratory.
• Patient who is not willing to attend the study visits or is not able to comply with follow-up visits up to 6 months.
• Known history of addiction/ alcohol abuse.
• Hypersensitivity to miltefosine or any study medication excipients.
• Patients with Sjogren-Larson Syndrome.

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead

Study Sites (6)

Fundación Nacional de Dermatología

Santa Cruz de la Sierra, Bolivia

Location

Instituto René Rachou Oswaldo Cruz Foundation- FIOCRUZ MINAS

Belo Horizonte, Minas Gerais, Brazil

Location

Julio Muller University Hospital Federal University of Mato Grosso

Cuiabá, Brazil

Location

Federal University of Bahia Immunology Department

Salvador, Brazil

Location

Instituto Conmemorativo Gorgas de Estudios de la Salud

Panama City, Provincia de Panamá, Panama

Location

Universidad Peruana Cayetano Heredia

Lima, Peru

Location

MeSH Terms

Conditions

Leishmaniasis, Cutaneous

Interventions

Meglumine Antimoniate; miltefosine

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)

Meglumine; Sorbitol; Sugar Alcohols; Alcohols; Organic Chemicals; Hexosamines; Amino Sugars; Carbohydrates

Study Officials

• Paulo Machado

  Federal University of Bahia

  PRINCIPAL INVESTIGATOR

• Marcia Hueb

  Julio Muller University Hospital Federal University of Mato Grosso

  PRINCIPAL INVESTIGATOR

• Fiorela Yuly Alvarez Romero

  Universidad Peruana Cayetano Heredia

  PRINCIPAL INVESTIGATOR

• Juan Miguel Pascale

  Instituto Conmemorativo Gorgas de Estudios de la Salud

  PRINCIPAL INVESTIGATOR

• Jaime Soto

  Fundación Nacional de Dermatología

  PRINCIPAL INVESTIGATOR

• Glaucia Cota

  Instituto René Rachou Oswaldo Cruz Foundation- FIOCRUZ MINAS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Initial, late responders and final cure assessments done in a blinded manner by the site clinicians at D90, D105 (if required) and D180, respectively.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2020
• First Posted: August 17, 2020
• Study Start: January 26, 2021
• Primary Completion: November 10, 2023
• Study Completion: February 27, 2024
• Last Updated: May 8, 2025

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

BO (1); BR (3); PE (1); PA (1)