Cutaneous Leishmaniasis
Conditions
Keywords
cutaneous leishmaniasis, topical treatment, Tunisia
Brief summary
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.
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.
Interventions
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.
Sponsors
Walter Reed Army Institute of Research (WRAIR)
U.S. Army Medical Research and Development Command
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Final Clinical Cure Rate for the Index Lesion | Final clincial cure is measured at day 98 | Number of index lesions with 100% reepithelialization at Day 98. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area of Index Lesions Throughout the Study | Measured at day 0, 20, 28, 42, and 98 | Area (mm\^2) of index lesion on Days 0, 20, 28, 42, and 98. |
| Number of Index Lesions With Reepithelialization Throughout the Study | Measured at day 28 and 42 | Number of index lesions with 100% reepithelialization on Days 28 and 42. |
| Area of All Ulcerated Lesions Throughout the Study | Measured at day 20, 28, 42 and 98 | Area of all ulcerated lesions on Days 20, 28, 42, and 98. |
| Number of All Ulcerated Lesions With Reepithelialization on Day 28 | Measured on day 28 | Final cure rate for all ulcerated lesions (100% reepithelialization for ulcerative lesions) on Day 28 |
Countries
Tunisia
Participant flow
Recruitment details
184 total screened and there were 134 screen failures.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Worsening of lesion | 1 |
Baseline characteristics
| Characteristic | WR 279,396 Topical Cream |
|---|---|
| Age, Continuous | 38.7 years STANDARD_DEVIATION 13.1 |
| Number of lesions per subject | 1.96 lesions STANDARD_DEVIATION 1.48 |
| Race/Ethnicity, Customized North African | 50 participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 50 |
| serious Total, serious adverse events | 0 / 50 |
Outcome results
Primary
Final Clinical Cure Rate for the Index Lesion
Number of index lesions with 100% reepithelialization at Day 98.
Time frame: Final clincial cure is measured at day 98
Population: modified intent to treat (mITT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WR 279,396 Topical Cream | Final Clinical Cure Rate for the Index Lesion | 48 lesions |
Secondary
Area of All Ulcerated Lesions Throughout the Study
Area of all ulcerated lesions on Days 20, 28, 42, and 98.
Time frame: Measured at day 20, 28, 42 and 98
Population: modified intent to treat (mITT). Baseline for this outcome measure does not include one subject (2 lesions) who withdrew on Day 18.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| WR 279,396 Topical Cream | Area of All Ulcerated Lesions Throughout the Study | Day 98 | 4.02 mm^2 | Standard Deviation 39.4 |
| WR 279,396 Topical Cream | Area of All Ulcerated Lesions Throughout the Study | Baseline (Day 0) | 82.6 mm^2 | Standard Deviation 90.4 |
| WR 279,396 Topical Cream | Area of All Ulcerated Lesions Throughout the Study | Day 20 | 288 mm^2 | Standard Deviation 275 |
| WR 279,396 Topical Cream | Area of All Ulcerated Lesions Throughout the Study | Day 28 | 149 mm^2 | Standard Deviation 198 |
| WR 279,396 Topical Cream | Area of All Ulcerated Lesions Throughout the Study | Day 42 | 22.1 mm^2 | Standard Deviation 63.3 |
Secondary
Area of Index Lesions Throughout the Study
Area (mm\^2) of index lesion on Days 0, 20, 28, 42, and 98.
Time frame: Measured at day 0, 20, 28, 42, and 98
Population: modified intent to treat (mITT). Baseline for this outcome measure does not include one subject (1 index lesion) who withdrew on Day 18.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| WR 279,396 Topical Cream | Area of Index Lesions Throughout the Study | Baseline (Day 0) | 121 mm^2 | Standard Deviation 106 |
| WR 279,396 Topical Cream | Area of Index Lesions Throughout the Study | Day 20 | 393 mm^2 | Standard Deviation 315 |
| WR 279,396 Topical Cream | Area of Index Lesions Throughout the Study | Day 28 | 203 mm^2 | Standard Deviation 238 |
| WR 279,396 Topical Cream | Area of Index Lesions Throughout the Study | Day 42 | 38.9 mm^2 | Standard Deviation 83.2 |
| WR 279,396 Topical Cream | Area of Index Lesions Throughout the Study | Day 98 | 7.88 mm^2 | Standard Deviation 55.1 |
Secondary
Number of All Ulcerated Lesions With Reepithelialization on Day 28
Final cure rate for all ulcerated lesions (100% reepithelialization for ulcerative lesions) on Day 28
Time frame: Measured on day 28
Population: modified intent to treat (mITT). This outcome measure does not include one subject (2 lesions) who withdrew on Day 18.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| WR 279,396 Topical Cream | Number of All Ulcerated Lesions With Reepithelialization on Day 28 | 23 lesions |
Secondary
Number of Index Lesions With Reepithelialization Throughout the Study
Number of index lesions with 100% reepithelialization on Days 28 and 42.
Time frame: Measured at day 28 and 42
Population: modified intent to treat (mITT). This outcome measure does not include one subject (2 lesions) who withdrew on Day 18.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| WR 279,396 Topical Cream | Number of Index Lesions With Reepithelialization Throughout the Study | Day 28 | 8 lesions |
| WR 279,396 Topical Cream | Number of Index Lesions With Reepithelialization Throughout the Study | Day 42 | 28 lesions |