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

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.

Study Overview

• Status: Terminated
• Conditions: Cutaneous Leishmaniasis
• Intervention / Treatment: Drug: Paromomycin +Gentamicin topical cream

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20307
      • Walter Reed Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paromomycin +Gentamicin topical cream; WR279,396 topically twice a day for 20 days	Drug: Paromomycin +Gentamicin topical cream; 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.; Other Names: WR279,396

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Collaborators: Walter Reed Army Medical Center
• Investigators: Principal Investigator: COL Naomi Aronson, M.D., Uniformed Services Univ of the Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2006
• Primary Completion (Actual): June 8, 2007
• Study Completion (Actual): June 24, 2010

Study Registration Dates

• First Submitted: February 22, 2008
• First Submitted That Met QC Criteria: April 8, 2008
• First Posted (Estimate): April 14, 2008

Study Record Updates

• Last Update Posted (Actual): January 22, 2019
• Last Update Submitted That Met QC Criteria: August 9, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Treatment; cutaneous; leishmaniasis; Old World; Leishmania major
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Euglenozoa Infections; Leishmaniasis; Leishmaniasis, Cutaneous; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Gentamicins; Paromomycin
• Other Study ID Numbers: A-13225

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided