WR 279,396 Open Label Treatment Protocol in Tunisia - Full Text View

Purpose

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.

Condition	Intervention	Phase
Cutaneous Leishmaniasis	Drug: WR 279,396 topical cream	Phase 2


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Open-label Treatment of Non-complicated, Non-severe, Cutaneous Leishmaniasis in Tunisia With WR 279,396 (Paromomycin + Gentamicin Topical Cream) )

Resource links provided by NLM:

MedlinePlus related topics: Leishmaniasis

Drug Information available for: Paromomycin sulfate Gentamicin Gentamicin sulfate Paromomycin

Genetic and Rare Diseases Information Center resources: Leishmaniasis

U.S. FDA Resources

Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:

Final Clinical Cure Rate for the Index Lesion [ Time Frame: Final clincial cure is measured at day 98 ] [ Designated as safety issue: No ]
Number of index lesions with 100% reepithelialization at Day 98.

Secondary Outcome Measures:

Area of Index Lesions Throughout the Study [ Time Frame: Measured at day 0, 20, 28, 42, and 98 ] [ Designated as safety issue: No ]
Area (mm^2) of index lesion on Days 0, 20, 28, 42, and 98.
Number of Index Lesions With Reepithelialization Throughout the Study [ Time Frame: Measured at day 28 and 42 ] [ Designated as safety issue: No ]
Number of index lesions with 100% reepithelialization on Days 28 and 42.
Area of All Ulcerated Lesions Throughout the Study [ Time Frame: Measured at day 20, 28, 42 and 98 ] [ Designated as safety issue: No ]
Area of all ulcerated lesions on Days 20, 28, 42, and 98.
Number of All Ulcerated Lesions With Reepithelialization on Day 28 [ Time Frame: Measured on day 28 ] [ Designated as safety issue: No ]
Final cure rate for all ulcerated lesions (100% reepithelialization for ulcerative lesions) on Day 28


Enrollment:	50
Study Start Date:	December 2011
Study Completion Date:	June 2012
Primary Completion Date:	June 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: WR 279,396 topical cream 120 subjects will be enrolled to this open label study to receive WR 279,396 topical cream	Drug: WR 279,396 topical cream 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. Other Names: WR 279, 396 Topical Paromomycin + Gentamicin Cream

Detailed Description:

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01494350

Locations


Tunisia
Central Clinic-Sidi Bouzid
Tunis, Tunisia

Sponsors and Collaborators

U.S. Army Medical Research and Materiel Command

Walter Reed Army Institute of Research (WRAIR)

Investigators


Principal Investigator:	Afif Ben Salah, M.D., Ph.D.	Institute Pasteur Tunisia

More Information


Responsible Party:	U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:	NCT01494350 History of Changes
Other Study ID Numbers:	S-10-0006; A-16898.3
Study First Received:	November 30, 2011
Results First Received:	December 9, 2014
Last Updated:	December 18, 2014
Health Authority:	United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:


cutaneous leishmaniasis topical treatment Tunisia

Additional relevant MeSH terms:


Leishmaniasis Leishmaniasis, Cutaneous Euglenozoa Infections Protozoan Infections Parasitic Diseases Skin Diseases, Parasitic Skin Diseases, Infectious Skin Diseases Paromomycin	Gentamicins Amebicides Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents Anti-Bacterial Agents Protein Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 26, 2016