Back to resultsTopical Treatment of Cutaneous Leishmaniasis With WR 279,396: A Phase 2 Study in the Old World
Primary Purpose
Cutaneous Leishmaniasis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
WR 279,396
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Cutaneous Leishmaniasis focused on measuring cutaneous leishmaniasis topical treatment safety efficacy
Eligibility Criteria
Inclusion Criteria:
- Age 5-75 years
- Lesions must measure at least 1 cm and be primarily ulcerative
- Have cutaneous leishmaniasis proven parasitologically in the lesion selected for study
- Must have given written informed consent to participate in the study
Exclusion Criteria:
- Known drug intolerance to aminoglycosides in the patient or immediate family
- Previous use of antileishmanial drugs (within 3 months) or present use of routinely nephrotoxic or ototoxic drugs
- Patients with tuberculosis under treatment
- Potential for follow-up: have less than 7 months time remaining in present address and/or plan to leave the area for more than 30 days
- Extent of disease: more than 5 lesions or lesion equal to or greater than 5 cm or a lesion less than 5 cm from the eye, 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 greater than 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:
- Hearing abnormality
- Ongoing pregnancy or have plans to become pregnant
- Females of child bearing age (Tunisia Only)
- Signs or symptoms of peripheral neuropathy
Kidney: clinically significant abnormalities of urine analysis, serum levels of creatinine, BUN, total proteins greater than the upper limit of normal for the laboratory.
Liver: AST or ALT greater than the upper limit of normal for the laboratory General: glucose, Na+, or K+ greater than the upper limit of normal for the laboratory
Sites / Locations
- Medical Center Institut Pasteur
- Institue Pasteur
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
WR 279,396
Placebo
Arm Description
WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin
Topical cream vehicle containing all of the components in WR 279,396 except the active ingredients.
Outcomes
Primary Outcome Measures
Complete Clinical Response (CCR) of Lesion at Days 50, 100 and 180 (+7 Days)
CCR is defined as at least 50% reduction, from baseline, in index lesion area of ulceration at study days 50, 100 and 180 (+ 7 days). Randomized subjects were compared using the uncorrected Fisher's exact test. Confidence intervals (95%) were constructed on the difference between the two group proportions. The log-rank test was used to compare the time to complete re-epithelialization of the index lesion without relapse. Cure of all subjects lesions was also compared using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable. The Breslow-Day test was used to examine whether the effect of WR 279,396 varied between subgroups
Safety of WR 279,396 (AEs and SAEs)
Safety was evaluated on each day during daily administration of the topical products. Subjects were observed and questioned for the occurrence of solicited local side effects (eg, pain, erythema, edema) and solicited systemic side effects (eg, vertigo, tinnitus, diminished hearing). Non-solicited AE evaluations included spontaneous reports from subjects and clinical observations.
Secondary Outcome Measures
Time to Complete Re-epithelialization of the Index Lesion Ulcer Without Relapse
100% re-epithelialization of the index lesion without having had a relapse. The log-rank test was used to compare the time to complete re-epithelialization.
Final Cure Rate by Subject of All Lesions
Final cure rate by subject was determined using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable.
Rate of Relapse
Relapse is defined as enlargement of the index lesion compared to previous measurement at any time after day 50 (+ 7 days) or not demonstrating CCR by study day 180. CCR was compared using uncorrected Fisher's exact test.
Confidence intervals (95%) were constructed on the difference between the two group proportions. The log-rank test was used to compare the time to complete re-epithelialization of the index lesion without relapse. Cure of all subjects lesions was also compared using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable.
Full Information
NCT ID
NCT00703924
First Posted
June 20, 2008
Last Updated
April 25, 2017
Sponsor
U.S. Army Medical Research and Development Command
Collaborators
Walter Reed Army Institute of Research (WRAIR)
1. Study Identification
Unique Protocol Identification Number
NCT00703924
Brief Title
Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: A Phase 2 Study in the Old World
Official Title
Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: a Phase 2 Study in the Old World
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
March 2003 (undefined)
Primary Completion Date
November 2004 (Actual)
Study Completion Date
November 2005 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
U.S. Army Medical Research and Development Command
Collaborators
Walter Reed Army Institute of Research (WRAIR)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is to determine the effectiveness and safety of WR 279,396, a topical cream for the treatment of cutaneous leishmaniasis. This study is to be conducted with a placebo control under double-blind conditions in a local population group in Tunisia where leishmaniasis is endemic.
Detailed Description
WR 279,396 is a paromomycin-based topical cream that has shown some suggestion of being effective for the treatment of non-serious, non-complicated cutaneous leishmaniasis in previous clinical studies. The goal of this study is to expand those observations in a larger, more rigorous study to clearly define the efficacy of this product and collect information about adverse effects. Subjects will be randomized to receive either WR 279,396 or vehicle placebo; applied twice a day for 20 days.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cutaneous Leishmaniasis
Keywords
cutaneous leishmaniasis topical treatment safety efficacy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
92 (Actual)
8. Arms, Groups, and Interventions
Arm Title
WR 279,396
Arm Type
Experimental
Arm Description
WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Topical cream vehicle containing all of the components in WR 279,396 except the active ingredients.
Intervention Type
Drug
Intervention Name(s)
WR 279,396
Other Intervention Name(s)
Paromomycin topical cream
Intervention Description
A topical cream containing 15% paromomycin and 0.5% gentamicin. Approximately 0.0005 mL per mm2 of skin lesion
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Topical vehicle placebo
Intervention Description
Topical cream vehicle. Approximately 0.0005 mL per mm2 of skin lesion
Primary Outcome Measure Information:
Title
Complete Clinical Response (CCR) of Lesion at Days 50, 100 and 180 (+7 Days)
Description
CCR is defined as at least 50% reduction, from baseline, in index lesion area of ulceration at study days 50, 100 and 180 (+ 7 days). Randomized subjects were compared using the uncorrected Fisher's exact test. Confidence intervals (95%) were constructed on the difference between the two group proportions. The log-rank test was used to compare the time to complete re-epithelialization of the index lesion without relapse. Cure of all subjects lesions was also compared using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable. The Breslow-Day test was used to examine whether the effect of WR 279,396 varied between subgroups
Time Frame
180 days
Title
Safety of WR 279,396 (AEs and SAEs)
Description
Safety was evaluated on each day during daily administration of the topical products. Subjects were observed and questioned for the occurrence of solicited local side effects (eg, pain, erythema, edema) and solicited systemic side effects (eg, vertigo, tinnitus, diminished hearing). Non-solicited AE evaluations included spontaneous reports from subjects and clinical observations.
Time Frame
180 days
Secondary Outcome Measure Information:
Title
Time to Complete Re-epithelialization of the Index Lesion Ulcer Without Relapse
Description
100% re-epithelialization of the index lesion without having had a relapse. The log-rank test was used to compare the time to complete re-epithelialization.
Time Frame
180 days
Title
Final Cure Rate by Subject of All Lesions
Description
Final cure rate by subject was determined using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable.
Time Frame
180 days
Title
Rate of Relapse
Description
Relapse is defined as enlargement of the index lesion compared to previous measurement at any time after day 50 (+ 7 days) or not demonstrating CCR by study day 180. CCR was compared using uncorrected Fisher's exact test.
Confidence intervals (95%) were constructed on the difference between the two group proportions. The log-rank test was used to compare the time to complete re-epithelialization of the index lesion without relapse. Cure of all subjects lesions was also compared using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable.
Time Frame
180 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 5-75 years
Lesions must measure at least 1 cm and be primarily ulcerative
Have cutaneous leishmaniasis proven parasitologically in the lesion selected for study
Must have given written informed consent to participate in the study
Exclusion Criteria:
Known drug intolerance to aminoglycosides in the patient or immediate family
Previous use of antileishmanial drugs (within 3 months) or present use of routinely nephrotoxic or ototoxic drugs
Patients with tuberculosis under treatment
Potential for follow-up: have less than 7 months time remaining in present address and/or plan to leave the area for more than 30 days
Extent of disease: more than 5 lesions or lesion equal to or greater than 5 cm or a lesion less than 5 cm from the eye, 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 greater than 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:
Hearing abnormality
Ongoing pregnancy or have plans to become pregnant
Females of child bearing age (Tunisia Only)
Signs or symptoms of peripheral neuropathy
Kidney: clinically significant abnormalities of urine analysis, serum levels of creatinine, BUN, total proteins greater than the upper limit of normal for the laboratory.
Liver: AST or ALT greater than the upper limit of normal for the laboratory General: glucose, Na+, or K+ greater than the upper limit of normal for the laboratory
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Afif Ben Salah, M.D., Ph.D.
Organizational Affiliation
Institute Pasteur Tunisia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical Center Institut Pasteur
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Institue Pasteur
City
Tunis
Country
Tunisia
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Data will be shared with WRAIR
Citations:
PubMed Identifier
19415122
Citation
Ben Salah A, Buffet PA, Morizot G, Ben Massoud N, Zaatour A, Ben Alaya N, Haj Hamida NB, El Ahmadi Z, Downs MT, Smith PL, Dellagi K, Grogl M. WR279,396, a third generation aminoglycoside ointment for the treatment of Leishmania major cutaneous leishmaniasis: a phase 2, randomized, double blind, placebo controlled study. PLoS Negl Trop Dis. 2009;3(5):e432. doi: 10.1371/journal.pntd.0000432. Epub 2009 May 5.
Results Reference
result
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Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: A Phase 2 Study in the Old World
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