Topical 3% Amphotericin B Cream for the Treatment of Cutaneous Leishmaniasis in Colombia (Anfoleish)

Safety, Pharmacokinetics, and Efficacy of Topical 3% Amphotericin B Cream for the Treatment of Uncomplicated Cutaneous Leishmaniasis in Colombia

The proposed study encompasses a two-step approach. The first aiming to determine the safety of Topical 3% Amphotericin B Cream when applied three or two times per day for 4 weeks in subjects with un-complicated Cutaneous leishmaniasis (CL) whilst the second focusing in having and indication of the efficacy of the two above mentioned regimens of Topical 3% Amphotericin B Cream

For the first step, 30 subjects will be randomly assigned to receive direct observed treatment (DOT) with Topical 3% Amphotericin B Cream applied either three or two times per day for 4 weeks. Enrolment will be temporarily halted until all 30 subjects (15 in each group) have been enrolled and completed the 28 day treatment course. An interim analysis of all safety (Adverse Events, including local reactions and lab parameters) and pharmacokinetics collected on subjects who were randomized will be performed by data safety monitoring board. If no serious adverse events (SAEs) related to the study drug are identified on the first 30 subjects by the end of the treatment course, 50 additional subjects will be randomly allocated to receive Topical 3% Amphotericin B Cream either three or two times per day for 28 days

Subjects will have a follow-up visit at the end of therapy, on Day 45± 5 days, Day 63± 5 days and on Days 90± 14 days and on Day 180, minus 14d, plus 4 weeks to assess efficacy, as measured by the number of subjects who fulfil the cure criteria: 100% re-epithelialization of the lesion(s) by Day 90 and no relapse by Day 180. All subjects will be followed up to Day 180 for final analysis of efficacy.

Study Overview

• Status: Completed
• Conditions: Cutaneous Leishmaniasis
• Intervention / Treatment: Drug: Topical Amphotericin B at 3%

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Colombia
  • Medellin, Colombia
    • Programa de Estudios y Control de Enfermedades Tropicales (PECET), Universidad de Antioquia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject with a confirmed infection due to L. braziliensis by polymerase chain reaction assay
• Subject has a lesion that satisfies the following criteria:
• ulcerative in character
• ulcer size equal or more than 0.5 cm and 3 cm (Longest diameter)
• not located on the ear, face, close to mucosal membranes, joints or on a location that in the opinion of the PI is difficult to maintain application of study drug topically.
• Subject with up to 3 lesions.
• Duration of lesion less than 3 months by patient history
• Subject able to give written informed consent and that the opinion of the investigator, the subject is capable of understanding and complying with the protocol

Exclusion Criteria:

• Female with a positive serum pregnancy test at screening or who is breast feeding, lactating or female at fertile age who does not agree to take appropriate contraception during treatment period up to Day 45.
• History of clinically significant medical problems or treatment that might interact, either negatively or positively, with topical treatment of leishmaniasis including any immunocompromising condition.
• Within 8 weeks (56 days) of starting study treatments, received treatment for 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.
• History of known or suspected hypersensitivity or idiosyncratic reactions to amphotericin
• Has laboratory values at screening as follow: Haemoglobin below 10 grams, Serum creatinine above normal level, alanine aminotransferase and or aspartate aminotransferase 3 times above normal range

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Topical Amphotericin B three times per day; Anfoleish applied 3 times per day for 4 weeks (TID group)	Drug: Topical Amphotericin B at 3%; Other Names: Anfoleish
Experimental: Topical Amphotericin B two times per day; Anfoleish applied 2 times per day for 4 weeks (BID group)	Drug: Topical Amphotericin B at 3%; Other Names: Anfoleish

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion and severity of local adverse events of Anfoleish or Vehicle when applied three or two times per day.	Local adverse events including erythema/redness, swelling/oedema, and vesicles will be scored according the following criteria: Grade 1: Visibly present but not associated with any other symptoms. Grade 2: Visibly present, large area around lesion site, and associated with other symptoms such as itching or pain. Medical intervention may be required. Grade 3: Severe symptoms that require medical discontinuation of the study drug.	At the end of treatment (Day 28)
Clinical cure rates in two regimens of Anfoleish: Three times a day and Two times a day	Cure is defined as 100% re-epithelialization of the lesion(s) by Day 90.	Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of Amphotericin B Cmax and Tmax in subjects treated with Anfoleish three or two times per day.		Day 45
Proportion and severity of laboratory adverse events of Anfoleish or vehicle when applied three or two times per day	Laboratory adverse events are limited to monitoring serum levels of creatinine, alanine aminotransferase and aspartate aminotransferase.	At the end of treatment (Day 28

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects showing a lesion's relapse by Day 180	Relapse defined as a lesion that achieved 100% re-epithelialization by Day 90 that subsequently reopened by Day 180.	Day 180

Collaborators and Investigators

• Sponsor: Drugs for Neglected Diseases
• Investigators: Principal Investigator: Ivan Dario Velez, Prof, PECET, Universidad de Antioquia, Medellin, Colombia

Publications and helpful links

General Publications

• Lopez L, Velez I, Asela C, Cruz C, Alves F, Robledo S, Arana B. A phase II study to evaluate the safety and efficacy of topical 3% amphotericin B cream (Anfoleish) for the treatment of uncomplicated cutaneous leishmaniasis in Colombia. PLoS Negl Trop Dis. 2018 Jul 25;12(7):e0006653. doi: 10.1371/journal.pntd.0006653. eCollection 2018 Jul.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: April 24, 2013
• First Submitted That Met QC Criteria: May 2, 2013
• First Posted (Estimate): May 3, 2013

Study Record Updates

• Last Update Posted (Estimate): July 26, 2016
• Last Update Submitted That Met QC Criteria: July 25, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Topical treatment; Cutaneous leishmaniasis; Colombia
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Euglenozoa Infections; Leishmaniasis; Leishmaniasis, Cutaneous; Anti-Infective Agents; Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Amphotericin B; Liposomal amphotericin B
• Other Study ID Numbers: DNDi-CL-TF001