Topical 3% Amphotericin B Cream for the Treatment of Cutaneous Leishmaniasis in Colombia (Anfoleish)
Primary Purpose
Cutaneous Leishmaniasis
Status
Completed
Phase
Phase 1
Locations
Colombia
Study Type
Interventional
Intervention
Topical Amphotericin B at 3%
Sponsored by
About this trial
This is an interventional treatment trial for Cutaneous Leishmaniasis focused on measuring Cutaneous leishmaniasis, Topical treatment, Colombia
Eligibility Criteria
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
Sites / Locations
- Programa de Estudios y Control de Enfermedades Tropicales (PECET), Universidad de Antioquia
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Topical Amphotericin B three times per day
Topical Amphotericin B two times per day
Arm Description
Anfoleish applied 3 times per day for 4 weeks (TID group)
Anfoleish applied 2 times per day for 4 weeks (BID group)
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Determination of Amphotericin B Cmax and Tmax in subjects treated with Anfoleish three or two times per day.
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.
Full Information
NCT ID
NCT01845727
First Posted
April 24, 2013
Last Updated
July 25, 2016
Sponsor
Drugs for Neglected Diseases
1. Study Identification
Unique Protocol Identification Number
NCT01845727
Brief Title
Topical 3% Amphotericin B Cream for the Treatment of Cutaneous Leishmaniasis in Colombia
Acronym
Anfoleish
Official Title
Safety, Pharmacokinetics, and Efficacy of Topical 3% Amphotericin B Cream for the Treatment of Uncomplicated Cutaneous Leishmaniasis in Colombia
Study Type
Interventional
2. Study Status
Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
February 2014 (undefined)
Primary Completion Date
May 2016 (Actual)
Study Completion Date
July 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Drugs for Neglected Diseases
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cutaneous Leishmaniasis
Keywords
Cutaneous leishmaniasis, Topical treatment, Colombia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Topical Amphotericin B three times per day
Arm Type
Experimental
Arm Description
Anfoleish applied 3 times per day for 4 weeks (TID group)
Arm Title
Topical Amphotericin B two times per day
Arm Type
Experimental
Arm Description
Anfoleish applied 2 times per day for 4 weeks (BID group)
Intervention Type
Drug
Intervention Name(s)
Topical Amphotericin B at 3%
Other Intervention Name(s)
Anfoleish
Primary Outcome Measure Information:
Title
Proportion and severity of local adverse events of Anfoleish or Vehicle when applied three or two times per day.
Description
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.
Time Frame
At the end of treatment (Day 28)
Title
Clinical cure rates in two regimens of Anfoleish: Three times a day and Two times a day
Description
Cure is defined as 100% re-epithelialization of the lesion(s) by Day 90.
Time Frame
Day 90
Secondary Outcome Measure Information:
Title
Determination of Amphotericin B Cmax and Tmax in subjects treated with Anfoleish three or two times per day.
Time Frame
Day 45
Title
Proportion and severity of laboratory adverse events of Anfoleish or vehicle when applied three or two times per day
Description
Laboratory adverse events are limited to monitoring serum levels of creatinine, alanine aminotransferase and aspartate aminotransferase.
Time Frame
At the end of treatment (Day 28
Other Pre-specified Outcome Measures:
Title
Proportion of subjects showing a lesion's relapse by Day 180
Description
Relapse defined as a lesion that achieved 100% re-epithelialization by Day 90 that subsequently reopened by Day 180.
Time Frame
Day 180
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ivan Dario Velez, Prof
Organizational Affiliation
PECET, Universidad de Antioquia, Medellin, Colombia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Programa de Estudios y Control de Enfermedades Tropicales (PECET), Universidad de Antioquia
City
Medellin
Country
Colombia
12. IPD Sharing Statement
Citations:
PubMed Identifier
30044792
Citation
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.
Results Reference
derived
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Topical 3% Amphotericin B Cream for the Treatment of Cutaneous Leishmaniasis in Colombia
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