WR 279,396 Open Label Treatment Protocol in Tunisia
Condition: Cutaneous Leishmaniasis
MeSH terms: Leishmaniasis; Leishmaniasis, Cutaneous
Intervention: WR 279,396 topical cream
Intervention description: 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.
Intervention MeSH terms: Gentamicins; Paromomycin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cutaneous leishmaniasis; topical treatment; Tunisia

Summary:

      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.
    

Eligibility criteria:

        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.