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Phase 3 Study of Walter Reed (WR) 279,396 and Paromomycin Alone for the Treatment of Cutaneous Leishmaniasis in Panama

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01790659
First Posted: February 13, 2013
Last Update Posted: August 23, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
  Purpose
This study is a pivotal Phase 3, randomized, double-blind, 3-site, two-group trial assessing the efficacy and safety of WR 279,396 Topical Cream and Paromomycin Alone Topical Cream in subjects with CL in Panama. The primary objective of this study is to determine if WR 279,396 results in statistically superior final clinical cure rates of an index lesion when compared with Paromomycin Alone for the treatment of CL in Panama expected to be caused by L panamensis.

Condition Intervention Phase
Cutaneous Leishmaniasis Drug: WR 279,396 Drug: Paromomycin Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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)


Enrollment: 399
Study Start Date: May 2013
Study Completion Date: January 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Experimental: Paromomycin
Paromomycin alone
Drug: Paromomycin
Paromomycin alone

Detailed Description:

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.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   2 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female at least 2 years-of-age
  • Subject or legal guardian able to give written informed consent or assent, as appropriate
  • Diagnosis of CL in at least one lesion by at least one of the following methods: 1) positive culture for promastigotes or 2) microscopic identification of amastigotes in stained lesion tissue
  • At least one ulcerative lesion ≥ 1 cm and ≤ 5 cm that has a diagnosis of CL
  • Willing to forego other forms of treatments for CL including other investigational treatments during the study
  • In the opinion of the investigator, subject (or their legal guardian), subject is capable of understanding and complying with the protocol
  • If female and of child-bearing potential, must have a negative serum pregnancy test during screening and agree to use an acceptable method of birth control during the treatment phase and for 1 week after treatment is completed

Exclusion Criteria:

  • Lesion due to leishmania that involves the nasal or oral mucosa or any signs of mucosal disease that might be due to Leishmania
  • Only a single lesion on the ear with erosive cartilage
  • Signs and symptoms of disseminated disease in the opinion of the investigator
  • More than 10 lesions
  • Female who is breast-feeding
  • Significant organ abnormality, chronic disease such as diabetes, severe hearing loss, evidence of renal or hepatic dysfunction, or creatinine, aspartate aminotransferase (AST), or alanine aminotransferase (ALT) greater than 15% above the upper limit of normal (ULN) as defined by the clinical laboratory defined normal ranges
  • Received treatment for leishmaniasis including any medication with pentavalent antimony including sodium stibogluconate (Pentostam™), meglumine antimoniate (Glucantime™); amphotericin B (including liposomal amphotericin B and amphotericin B deoxycholate); or other medications containing paromomycin (administered parenterally or topically) or methylbenzethonium chloride (MBCL); gentamicin; fluconazole; ketoconazole; pentamidine; miltefosine, azithromycin or allopurinol that was completed within 56 days of starting study treatments
  • History of known or suspected hypersensitivity or idiosyncratic reactions to aminoglycosides
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01790659


Locations
Panama
Instituto Conmemorativo Gorgas de Estudios de la Salud,
Panama City, Panama
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
Investigators
Principal Investigator: Nestor Sosa, MD, FACP Instituto Conmemorativo Gorgas de Estudios de la Salud
  More Information

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01790659     History of Changes
Other Study ID Numbers: S-12-21
First Submitted: February 5, 2013
First Posted: February 13, 2013
Results First Submitted: October 11, 2016
Results First Posted: August 23, 2017
Last Update Posted: August 23, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by U.S. Army Medical Research and Materiel Command:
leishmaniasis
cutaneous leishmaniasis
Leishmania panamensis
L panamensis
Paromomycin
Paromomycin/Gentamicin

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