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

• ClinicalTrials.gov Identifier: NCT00657917
• Recruitment Status: Terminated
• First Posted: April 14, 2008
• Results First Posted: January 22, 2019
• Last Update Posted: January 22, 2019
• Sponsor: U.S. Army Medical Research and Development Command
• Collaborator: Walter Reed Army Medical Center
• Information provided by (Responsible Party): U.S. Army Medical Research and Development Command

Tracking Information

• First Submitted Date: February 22, 2008
• First Posted Date: April 14, 2008
• Results First Submitted Date: May 2, 2017
• Results First Posted Date: January 22, 2019
• Last Update Posted Date: January 22, 2019
• Actual Study Start Date: December 20, 2006
• Actual Primary Completion Date: June 8, 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 9, 2018)

The Appearance of Complete Epithelialization of Ulcerative Lesions Caused by Old World Cutaneous Leishmaniasis With no Relapse [ Time Frame: 180 days ]

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.

• Original Primary Outcome Measures (submitted: April 8, 2008): The primary outcome is the re-epithelialization of ulcerative lesions caused by Old World cutaneous leishmaniasis with no relapse [ Time Frame: 180 days ]

Current Secondary Outcome Measures (submitted: August 9, 2018)

• Number of Relapses [ Time Frame: 180 days ]
  Evaluate the number of relapses occurring by day 180
• Safety and Tolerability (SAE's and AE's) [ Time Frame: 180 days ]
  Evaluate safety and tolerability as measured by completion of a full prescribed treatment course, treatment interruptions, SAE's and AE's

• Original Secondary Outcome Measures (submitted: April 8, 2008): the secondary outcome is to determine if there are any local or systemic signs of toxicity, and if so to grade them. [ Time Frame: 180 days ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Topical Treatment of Recalcitrant Ulcerative Old World Leishmaniasis With WR 279,396
• Official Title: Topical Treatment of Recalcitrant Ulcerative Old World Leishmaniasis With WR 279,396
• Brief Summary: 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: 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
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cutaneous Leishmaniasis

Intervention

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 Name: WR279,396

Study Arms

Experimental: Paromomycin +Gentamicin topical cream

WR279,396 topically twice a day for 20 days

Intervention: Drug: Paromomycin +Gentamicin topical cream

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: March 1, 2011): 1
• Original Estimated Enrollment (submitted: April 8, 2008): 10
• Actual Study Completion Date: June 24, 2010
• Actual Primary Completion Date: June 8, 2007 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00657917
• Other Study ID Numbers: A-13225
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: U.S. Army Medical Research and Development Command
• Original Responsible Party: Director, Division of Regulated Activities and Compliance, U.S. Army Medical Materiel Development Activity
• Current Study Sponsor: U.S. Army Medical Research and Development Command
• Original Study Sponsor: Same as current
• Collaborators: Walter Reed Army Medical Center

Investigators

• Principal Investigator: COL Naomi Aronson, M.D.; Uniformed Services Univ of the Health Sciences

• PRS Account: U.S. Army Medical Research and Development Command
• Verification Date: August 2018