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A Study to Evaluate the Efficacy and Tolerance of WR279,396 for Old World Cutaneous Leishmaniasis

Primary Purpose

Old World Cutaneous Leishmaniasis

Status

Completed

Phase

Phase 2

Locations

Tunisia

Study Type

Interventional

Intervention

WR279,396 with Tegaderm Dressing

WR 279,396 with Gauze and Tape Dressing

About this trial

This is an interventional treatment trial for Old World Cutaneous Leishmaniasis focused on measuring Ointment to treat leishmania skin lesions

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: The study population will be selected from adults (18y) patients and children above 15y in Tunisia (Old World)

Age: 15 - 75 years old
Lesion character: each diameter (horizontal and vertical) of the lesion test must measure 7 mm, the lesion must be primarily ulcerative (i.e., not verrucous or nodular) and located in a biopsy friendly site of the body
Parasitological diagnosis: have cutaneous leishmaniasis proven parasitologically in lesion selected for inclusion in study (lesion test).
Informed consent: have given written informed consent to participate in the study: (i.e. patient or legal representative).

Exclusion Criteria:

Drug intolerance: history of known or suspected hypersensitivity or idiosyncratic reactions to aminoglycosides in the patient or immediate family members.
Previous use of antileishmanial drugs (within 2 months) or present use of routinely nephrotoxic or ototoxic drugs.
Potential for follow up: Have less than 4 months time remaining in present address and/or plans to leave the area for more than 30 days.
Extent of disease: More than 10 lesions or lesion ³ 5 cm or a lesion less than 2 cm from eye, in the ear, or a lesion in the face, that in the opinion of the attending dermatologist could potentially cause significant disfigurement.
Location of disease: mucosal involvement.
Disseminated disease: clinically significant lymphadenitis with nodules that are painful and > 1 cm in size in the lymphatic drainage of the ulcer.
Concomitant medical problems: significant medical problems of the kidney or liver as determined by history and by the following laboratory studies:
Kidney: clinically significant abnormalities of urine analysis, serum levels of Creatinine, BUN, total proteins > upper limit of normal for the laboratory.
Liver: AST or ALT > upper limit of normal for the laboratory.
General: glucose, Na, K, > upper limit of normal or < lower limit of normal for the laboratory. Volunteers in whom these normal laboratory values are exceeded by less than 25% will not be automatically excluded. These volunteers will be evaluated on the basis of history, physical, as well as laboratory values.
Scheduled or ongoing pregnancy as determined clinical and biological criteria.
Presence of signs or symptoms of peripheral neuropathy, myasthenia gravis or neuromuscular block

Sites / Locations

Institut Pasteur

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

WR279,396 with Tegaderm dressing

WR279,396 with Gauze and Tape Dressing

Arm Description

24 patients will be randomly allocated to WR279,396 treatment once-a-day for 20 days with using an occlusive polyurethane Tegaderm dressing

24 subjects will be randomly allocated to WR279,396 treatment once a day for 20 days without an optimized polyurethane dressing (gauze and tape only).

Outcomes

Primary Outcome Measures

Safety: Overview of Adverse Events

Safety of WR279,396 through the tracking of local, systemic and spontaneous adverse reactions

Secondary Outcome Measures

Clinical Responses of Index Lesions (100% Re-epithelialization)

Efficacy will be evaluated in terms of the number of lesions cured at D50 (D1 is the first day of treatment) with no relapse by Day 90. Complete clinical respoonse is defined as 100% re-epithelialization of the index lesion by Day 50 or a > 50% re-epithelialization by Day 50 followed by complete re-epithelialization on or before Day 90, with no relapse ever having occurred from Day 50 through Day 90.

Full Information

NCT ID

NCT01536795

First Posted

February 16, 2012

Last Updated

February 10, 2021

Sponsor

U.S. Army Medical Research and Development Command

1. Study Identification

Unique Protocol Identification Number

NCT01536795

Brief Title

A Study to Evaluate the Efficacy and Tolerance of WR279,396 for Old World Cutaneous Leishmaniasis

Official Title

Topical Treatment of Old World Cutaneous Leishmaniasis With WR279396 (Paromomycin/Gentamicin Ointment): Efficacy and Tolerance of a Regimen Using an Occlusive Polyurethane Dressing

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Completed

Study Start Date

October 2005 (Actual)

Primary Completion Date

February 2007 (Actual)

Study Completion Date

February 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

U.S. Army Medical Research and Development Command

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This Phase 2 study is to determine whether WR279396 with occlusion (a polyurethane dressing) is more effective than WR279396 without occlusion for once daily treatment. Extensive objective and subjective local tolerance data will also be captured during this trial, as well as surrogate markers (parasite loads and aminoglycosides concentration in the deep dermis) that may help to determine the optimal number and duration of treatments. The results from this study will help determine the most practical treatment schedule and will answer questions that are crucial to improve the present treatment regimen with WR279396 which is twice a day for 20 days.

Detailed Description

Forty-eight patients (48) with Old World cutaneous leishmaniasis will be randomly allocated to WR279396 treatment once a day for 20 days with an optimized polyurethane dressing (occlusion) (24 patients), or without occlusion (24 patients). All patients will be rescued with the standard of care accepted in Tunisia, if the patient is not cured. The active ingredients of WR279396 are two aminoglycosides - paromomycin sulphate (15%) and gentamicin sulphate (0.5%) - in a base (AQIC). Each subject will be followed for clinical cure for 90 days after the initiation of treatment. Cure is defined as 100% reepithelialization without relapse by 3 months. Tolerance will be evaluated by local adverse reactions and by laboratory signs of systemic events. In addition to the clinical evaluation of the CL lesions, the following parameters/clinical healing surrogates will be investigated: parasite load will be determined in superficial and deep lesional dermis samples at D0 and D10. The mean parasite reduction ratio (parasite load at D10/parasite load at D0) in each group will be compared; aminoglycoside concentrations in superficial and deep infiltrated dermis in each group will be compared.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Old World Cutaneous Leishmaniasis

Keywords

Ointment to treat leishmania skin lesions

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

WR279,396 with Tegaderm dressing

Arm Type

Experimental

Arm Description

24 patients will be randomly allocated to WR279,396 treatment once-a-day for 20 days with using an occlusive polyurethane Tegaderm dressing

Arm Title

WR279,396 with Gauze and Tape Dressing

Arm Type

Experimental

Arm Description

24 subjects will be randomly allocated to WR279,396 treatment once a day for 20 days without an optimized polyurethane dressing (gauze and tape only).

Intervention Type

Drug

Intervention Name(s)

WR279,396 with Tegaderm Dressing

Intervention Description

Ointment containing paromomycin sulphate (15%) and gentamicin sulphate (0.5%) - in a base (AQIC)applied for 20 days with polyurethane dressing

Intervention Type

Drug

Intervention Name(s)

WR 279,396 with Gauze and Tape Dressing

Intervention Description

Ointment containing paromomycin sulphate (15%) and gentamicin sulphate (0.5%) - in a base (AQIC)applied for 20 days

Primary Outcome Measure Information:

Title

Safety: Overview of Adverse Events

Description

Safety of WR279,396 through the tracking of local, systemic and spontaneous adverse reactions

Time Frame

During 20 day treatment period

Secondary Outcome Measure Information:

Title

Clinical Responses of Index Lesions (100% Re-epithelialization)

Description

Time Frame

Day 50, 90

Other Pre-specified Outcome Measures:

Title

Area of the Index Lesion's Ulceration by Study Day

Description

Area of the index lesion's ulceration over time in mm2

Time Frame

Days 1, 10, 20, 50 and 90

Title

Area of the Index Lesion's Induration by Study Day

Description

Area of the index lesion's induration over time in mm2

Time Frame

Days 1, 10, 20, 50 and 90

Title

Percentage Change in Induration Area From Baseline and Days 10, 20, 50 and 90

Description

Percentage of change of index lesion in induration area from baseline and days 10, 20, 50 and 90

Time Frame

Days 10, 20, 50 and 90

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: The study population will be selected from adults (18y) patients and children above 15y in Tunisia (Old World) Age: 15 - 75 years old Lesion character: each diameter (horizontal and vertical) of the lesion test must measure 7 mm, the lesion must be primarily ulcerative (i.e., not verrucous or nodular) and located in a biopsy friendly site of the body Parasitological diagnosis: have cutaneous leishmaniasis proven parasitologically in lesion selected for inclusion in study (lesion test). Informed consent: have given written informed consent to participate in the study: (i.e. patient or legal representative). Exclusion Criteria: Drug intolerance: history of known or suspected hypersensitivity or idiosyncratic reactions to aminoglycosides in the patient or immediate family members. Previous use of antileishmanial drugs (within 2 months) or present use of routinely nephrotoxic or ototoxic drugs. Potential for follow up: Have less than 4 months time remaining in present address and/or plans to leave the area for more than 30 days. Extent of disease: More than 10 lesions or lesion ³ 5 cm or a lesion less than 2 cm from eye, in the ear, or a lesion in the face, that in the opinion of the attending dermatologist could potentially cause significant disfigurement. Location of disease: mucosal involvement. Disseminated disease: clinically significant lymphadenitis with nodules that are painful and > 1 cm in size in the lymphatic drainage of the ulcer. Concomitant medical problems: significant medical problems of the kidney or liver as determined by history and by the following laboratory studies: Kidney: clinically significant abnormalities of urine analysis, serum levels of Creatinine, BUN, total proteins > upper limit of normal for the laboratory. Liver: AST or ALT > upper limit of normal for the laboratory. General: glucose, Na, K, > upper limit of normal or < lower limit of normal for the laboratory. Volunteers in whom these normal laboratory values are exceeded by less than 25% will not be automatically excluded. These volunteers will be evaluated on the basis of history, physical, as well as laboratory values. Scheduled or ongoing pregnancy as determined clinical and biological criteria. Presence of signs or symptoms of peripheral neuropathy, myasthenia gravis or neuromuscular block

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Afif Ben Salah,, MD, PhD

Organizational Affiliation

Institut Pasteur, Tunisia

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institut Pasteur

City

Tunis

Country

Tunisia

12. IPD Sharing Statement

Plan to Share IPD

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A Study to Evaluate the Efficacy and Tolerance of WR279,396 for Old World Cutaneous Leishmaniasis

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