Phase 3 Study of Walter Reed (WR) 279,396 and Paromomycin Alone for the Treatment of Cutaneous Leishmaniasis in Panama
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-blind, Pivotal Phase 3 Study of WR 279,396 (Paromomycin + Gentamicin Topical Cream) and Paromomycin Alone Topical Cream for the Treatment of Cutaneous Leishmaniasis in Panama|
- Final Clinical Cure Change From Baseline [ Time Frame: baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days ]
The primary efficacy endpoint is number of subjects with final clinical cure. Final clinical cure is defined as follows:
- Subject has initial clinical cure (100% re-epithelialization of index lesion by nominal Day 63); OR,
- Subject has initial clinical improvement (> 50% re-epithelialization of index lesion by nominal Day 63) followed by 100% re-epithelialization of the index lesion on or before nominal Day 100; AND,
- Subject has no relapse of index lesion.
- Percentage of Subjects With All Lesions Cured [ Time Frame: 168 ± 14 days ]• Percentage of subjects with all lesions cured, defined as: Final clinical cure as defined in primary objective (which is based solely on the index lesion); AND, Cure of all other lesions by nominal Day 168 (100% re-epithelialization of all ulcerated lesions and resolution of all other types of lesions)
- Percentage of All Lesions Cured at Day 168 (Ignores Per Subject Cure Rate) [ Time Frame: Day 168 ]Percentage of all lesions meeting criteria for clinical cure during the study at 168 day mark for mITT subjects
- Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point [ Time Frame: baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days ]Area of ulceration (mm^2) of the index lesion at each measurement time point for mITT subjects
- Area of Ulceration (mm^2) All Treated Lesions at Each Measurement Time Point [ Time Frame: baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days ]Area of ulceration (mm^2) of all treated lesions from baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days for mITT subjects. Data presented is as presented in the FCSR; any inconsistencies can't be changed.
- Number of All Lesions Meeting Criteria for Clinical Cure [ Time Frame: baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days ]Number of all lesions meeting criteria for clinical cure at each visit - evaluable subjects. Cure is defined as 100% re-epithelialization of an ulcerated lesion
- Median Time to Initial Clinical Cure for Index Lesions [ Time Frame: When 100% re-epithelialization of the index lesion is observed at any visit Study Days (20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days ]Median time to initial clinical cure for index lesions (100% re-epithelialization of the index lesion)
|Study Start Date:||May 2013|
|Study Completion Date:||January 2016|
|Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Experimental: WR 279,396
(Paromomycin and Gentamicin Topical Cream)
Drug: WR 279,396
WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%
Other Name: Paromomycin/Gentamicin topical cream
Subjects will be recruited from three regions in Panama known to be endemic for L panamensis CL. Subjects will be screened over a period up to 28 days for eligibility including medical history, physical examination, leishmaniasis history, vital signs, clinical chemistry, prior medications, and parasitology for confirmation of ulcerative CL. If eligible, subjects will be randomized in a targeted 1:1 ratio (200 subjects per group) using site as a stratification variable to receive either WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream) or Paromomycin Alone (15% paromomycin topical cream) by topical application to CL lesions once daily for 20 days. Efficacy will be assessed by measuring the size of the index lesion ulcer, non-index lesions ulcers, and overall size of other non-ulcerated lesions at baseline (before the start of treatment), and on Study Days 20, 35 ± 2 days, 49 ± 4 days, 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days. A notation will be made if clinical evidence of parasite persistence is observed at the Day 63 and beyond visits including significant erythema and induration when a lesion has otherwise completely re-epithelialized to document any subjects removed from the study early if the investigator judges them to be in need of rescue treatment. A photograph will be taken of all lesions at baseline, Day 20 and each of the follow-up visits. Safety will be assessed by monitoring adverse events (AEs) from the start of treatment until study completion, lesion site reactions during treatment, physical examination of the nasal and oral mucosa for appearance of mucosal leishmaniasis on Days 63 ± 7 days, 100 ± 14 days, and 168 ± 14 days, concomitant medication use for the duration of the study, blood creatinine, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels on Study Day 20. After the sponsor's approval, biochemistry can be repeated in the case of abnormal results and if the causes of these results could not be determined. A repeat pregnancy test on Day 35. Recent infection with leishmaniasis prior to the start of the study may result in the development of lesions that were not present at the start of the study that did not receive treatment. New lesions may be treated at the discretion of the investigator with the topical cream to which the subject was assigned any time during the conduct of the study except that treatment must be completed by the Day 168 visit. If a new lesion is discovered at the final study visit, the subject will be referred to their primary physician for treatment.
Subjects who fail therapy (see definition of failure below) will be taken off study and may be administered rescue therapy at the discretion of the subject's personal physician. If the subject met the criteria for therapy failure but was undergoing treatment for new lesions, the subject can continue in the study (by signing a consent addendum) if the investigator decides it is in the best interest of the subject to do so.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01790659
|Instituto Conmemorativo Gorgas de Estudios de la Salud,|
|Panama City, Panama|
|Principal Investigator:||Nestor Sosa, MD, FACP||Instituto Conmemorativo Gorgas de Estudios de la Salud|