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

NCT01845727 | Completed Phase 1

• 1 other identifier: DNDi-CL-TF001
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cutaneous Leishmaniasis

Keywords

Cutaneous leishmaniasis; Topical treatment; Colombia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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

  At the end of treatment (Day 28

Other Outcomes (1)

• Proportion of subjects showing a lesion's relapse by Day 180

  Day 180

Study Arms (2)

Topical Amphotericin B three times per day

EXPERIMENTAL

Anfoleish applied 3 times per day for 4 weeks (TID group)

Drug: Topical Amphotericin B at 3%

Topical Amphotericin B two times per day

EXPERIMENTAL

Anfoleish applied 2 times per day for 4 weeks (BID group)

Drug: Topical Amphotericin B at 3%

Interventions

Topical Amphotericin B at 3% DRUG

Also known as: Anfoleish

Topical Amphotericin B three times per day; Topical Amphotericin B two times per day

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead

Study Sites (1)

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

Medellín, Colombia

Location

Related Publications (1)

• 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.

  PMID: 30044792 DERIVED

MeSH Terms

Conditions

Leishmaniasis, Cutaneous

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

Study Officials

• Ivan Dario Velez, Prof

  PECET, Universidad de Antioquia, Medellin, Colombia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2013
• First Posted: May 3, 2013
• Study Start: February 1, 2014
• Primary Completion: May 1, 2016
• Study Completion: July 1, 2016
• Last Updated: July 26, 2016

Record last verified: 2016-07

Locations

CO (1)