Topical Treatment of Recalcitrant Ulcerative Old World Leishmaniasis With WR 279,396

Study Overview
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Brief Summary
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The primary objective of this protocol is to treat laboratory confirmed cutaneous leishmaniasis with WR 279,396 in military health care beneficiaries. In this study cutaneous leishmaniasis is defined as Old World Leishmaniasis if acquired in the Southwest Central Asia/Middle East.

Detailed Description
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Up to 10 volunteers, who are military health care beneficiaries, with a diagnosis of Old World cutaneous leishmaniasis who have failed pentavalent antimony or are not eligible to be treated with pentavalent antimony, will be treated with WR 279,396 (topical paromomycin-gentamicin-AQIC) twice a day for 20 days. Primary endpoint will be the appearance of complete epithelialization of each skin lesion by Day 50+/-2 weeks, or estimated 50%-99% re-epithelialization by Day 50+/-2 weeks followed by complete epithelialization by Day 100+/-2 weeks,with both categories without relapse by Day 180+/-30 days. Efficacy will be evaluated by clinical appearance assessed by study investigator and documented with photographs of the treated skin lesions. Toxicity will be evaluated by local adverse reactions and by laboratory signs of systemic toxicity.

Official Title
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Topical Treatment of Recalcitrant Ulcerative Old World Leishmaniasis With WR 279,396

Conditions
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Cutaneous Leishmaniasis

Intervention / Treatment
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* Drug: Paromomycin +Gentamicin topical cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parasitologically confirmed, primarily ulcerative, Old World CL, in a patient who had either failed pentavalent antimony treatment, or who was ineligible for pentavalent antimony therapy. Military health care beneficiary 18 years of age or greater, unless active military in which case, 17 years is the minimum age Proven parasitological diagnosis by culture, PCR or microscopy in at least one skin lesion Lesions primarily ulcerative (i.e., not verrucous or nodular) Written informed consent to participate in protocol Negative pregnancy test within 72 hours of starting protocol Agrees to take precautions not to become pregnant or father a child for at least two months after completion of treatment with WR 279,396 Cutaneous leishmaniasis acquired in Southwest Central Asia/Middle East* Inadequate response to treatment with pentavalent antimony or medical condition that precludes the use of pentavalent antimony Exclusion Criteria: Drug intolerance: history of known or suspected hypersensitivity or idiosyncratic reactions to aminoglycosides in the patient any leishmanial lesion on mucosal surface Presence of signs or symptoms of peripheral neuropathic myasthenia gravis, neuromuscular block Routinely taking nephrotoxic or ototoxic medications Disseminated disease defined as clinically significant subcutaneous nodules that are in the lymphatic drainage tract for the skin lesion with regional adenopathy > 1 cm Abnormal Romberg test at baseline Clinically significant medical problems of the kidney or liver as determined by history and by the following laboratory studies: Kidney: Creatinine > 2x the upper limit of normal Liver: ASTor ALT >4x the upper limit fo normal This includes L. major, L. tropica, and L. infantum with over 98% of cases in U.S. military in 2002-2004 being L. major An inadequate response to treatment with pentavalent antimony includes patients who show no or little improvement during a 15-20 day treatment course, those that initially epithelialize but later show signs of breakdown/ ulceration or develop new lesions. In general, for those with initial treatment response, would recommend waiting for approximately two months after pentavalent antimony and if lesion is not epithelialized at that time, consideration for further therapy is advised.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paromomycin +Gentamicin topical cream<br>WR279,396 topically twice a day for 20 days | Drug: Paromomycin +Gentamicin topical cream<br>* WR297,396 for treatment of patients with parasitologically confirmed, primarily ulcerative, Old World CL, who had either failed pentavalent antimony treatment, or who where ineligible for pentavalent antimony therapy.<br>* Other names: WR279,396;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Appearance of Complete Epithelialization of Ulcerative Lesions Caused by Old World Cutaneous Leishmaniasis With no Relapse | Appearance of complete (100%) epithelialization of a skin lesion at day 50+2 weeks, or the estimated 50%-99% re-epithelialization by day 50+2 weeks followed by complete eipithelialization by day 100+2 weeks, with both categories without relapse by day 180+30 days. Ulcer measured in millimeters. | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Relapses | Evaluate the number of relapses occurring by day 180 | 180 days | 
| Safety and Tolerability (SAE's and AE's) | Evaluate safety and tolerability as measured by completion of a full prescribed treatment course, treatment interruptions, SAE's and AE's | 180 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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leishmaniasis, cutaneous, Old World, Leishmania major, Treatment