WR 279,396 Open Label Treatment Protocol in Tunisia

Study Overview
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Brief Summary
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The U.S. Army has recently completed a Phase 3 clinical trial in Tunisia. This is an open-label single site trial designed to expand our safety database and capture additional efficacy (final clinical cure rate of an index lesion) of WR 279,396 Topical Cream in Tunisian subjects with non-complicated, non-severe Cutaneous Leishmaniasis (CL). Subjects will be patients who visit Ministry of Health sponsored clinics in Tunisia who present with at least one CL lesion that is ulcerated and amenable to topical treatment. Potential trial subjects will be consented and screened for eligibility including medical history, physical exam, lesion parasitology, and renal and liver function tests. If eligible for the study, subjects will receive WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream) (target n = 110). The cream will be applied topically to all CL lesions once daily for 20 days by an investigator or study nurse. If a subject develops a new lesion during the study, the new lesion may also be treated with the topical cream.

Detailed Description
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Subjects will have an in-clinic follow-up on Days 28 +/- 2 days, 42 +/- 4 days and 98 +/- 8 days to assess safety and cure rates. Safety variables including adverse events (AEs) and serious adverse events (SAEs) will be collected through Day 98. For the primary efficacy evaluation, the index ulcerative lesion will be assessed for clinical response by measurement of the length and width of area of ulceration. All other treated lesions will also be assessed for cure as secondary efficacy endpoints with ulcerated and non-ulcerated lesions being evaluated independently. An ulcerated lesion will be considered to be completely cured if 100% reepithelialization is observed. The length and width of non-ulcerated lesions (nodules, plaques) will also be measured and evaluated for cure (ie, absence of signs of an active lesion). The primary efficacy endpoint is the final clinical cure rate calculated by the number of index lesions that had 100% reepithelialization at Day 98 divided by the total number of index lesions that received at least one topical treatment of WR 279,396.

Official Title
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Open-label Treatment of Non-complicated, Non-severe, Cutaneous Leishmaniasis in Tunisia With WR 279,396 (Paromomycin + Gentamicin Topical Cream) )

Conditions
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Cutaneous Leishmaniasis

Intervention / Treatment
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* Drug: WR 279,396 topical cream


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age Subject has a 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) positive culture for promastigotes. Subject has a parasitologically confirmed lesion that satisfies the following criteria for an Index lesion: ulcerative in character lesion size ≥ 1 cm and ≤5 cm (including the area of induration surrounding the lesion) not located on the ear, or on a location that in the opinion of the PI is difficult to maintain application of study drug topically. Subject has < 7 leishmaniasis total lesions. Subject is willing to forego other forms of treatments for CL including other investigational treatments during the study. In the opinion of the investigator, the subject (or their legal guardian) is capable of understanding and complying with the protocol. Exclusion Criteria: Female with a positive serum pregnancy test or who is breast feeding. History of clinically significant medical problems in the investigator's judgment that might interact, either negatively or positively, with topical treatment of leishmaniasis including any immunocompromising condition. Age adjusted blood creatinine or blood urea nitrogen (BUN) levels indicative of clinically significant renal disease or aspartate amino transferase (AST), alanine amino transferase (ALT), or total bilirubin that suggest clinically significant hepatic impairment as judged by the PI or subinvestigator. Note: This study is designed to evaluate populations who may have some renal or hepatic dysfunction as the drug has not been shown to have serum levels that would be expected to show renal or hepatic toxicity and treatment of the general population presenting with CL is highly desired based on its safety profile compared to other leishmanial drugs. Evidence of disseminated leishmaniasis. Received treatment for leishmaniasis with antimonials or any medication likely, in the opinion of the PI, to modify the course of the Leishmania infection within 56 days of starting study treatments. History of known or suspected hypersensitivity or idiosyncratic reactions to aminoglycosides.

Ages Eligible for Study
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Minimum Age: 18 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: WR 279,396 topical cream<br>120 subjects will be enrolled to this open label study to receive WR 279,396 topical cream | Drug: WR 279,396 topical cream<br>* WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin that will be applied to each lesion once a day for 20 days and covered with a sterile gauze and tape dressing.<br>* Other names: Topical Paromomycin + Gentamicin Cream;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Final Clinical Cure Rate for the Index Lesion | Number of index lesions with 100% reepithelialization at Day 98. | Final clincial cure is measured at day 98 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area of Index Lesions Throughout the Study | Area (mm^2) of index lesion on Days 0, 20, 28, 42, and 98. | Measured at day 0, 20, 28, 42, and 98 | 
| Number of Index Lesions With Reepithelialization Throughout the Study | Number of index lesions with 100% reepithelialization on Days 28 and 42. | Measured at day 28 and 42 | 
| Area of All Ulcerated Lesions Throughout the Study | Area of all ulcerated lesions on Days 20, 28, 42, and 98. | Measured at day 20, 28, 42 and 98 | 
| Number of All Ulcerated Lesions With Reepithelialization on Day 28 | Final cure rate for all ulcerated lesions (100% reepithelialization for ulcerative lesions) on Day 28 | Measured on day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cutaneous leishmaniasis, topical treatment, Tunisia