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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2014 by U.S. Army Medical Research and Materiel Command
Sponsor:
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT01790659
First received: February 5, 2013
Last updated: December 17, 2014
Last verified: December 2014
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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 ] [ Designated as safety issue: No ]

    The primary efficacy endpoint is percentage 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: 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 ] [ Designated as safety issue: No ]
    • 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 100 (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 ] [ Designated as safety issue: No ]
  • Area of ulceration 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 ] [ Designated as safety issue: No ]
  • Area of ulceration 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 ] [ Designated as safety issue: No ]
  • Ulcerated lesion cure rate 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 ] [ Designated as safety issue: No ]
    (cure is defined as 100% re-epithelialization of an ulcerated lesion)

  • Median time to initial clinical cure [ Time Frame: to be determined ] [ Designated as safety issue: No ]
    (100% re-epithelialization of the index lesion)

  • adverse events (AEs) /serious adverse events (SAEs) (clinical signs and symptoms) [ Time Frame: AEs will be assessed at baseline, days 2-9 daily, day 20, day 35, 49, 63, 100, and 168 (if applicable) ] [ Designated as safety issue: Yes ]
    AEs including application site reactions including elicited examination for pain, and clinician examination for erythema/redness, swelling/edema, and vesicles. Physical examination findings of evidence of mucosal leishmaniasis will be reported as an AE

  • Significant lab abnormalities [ Time Frame: baseline screening and day 20 ] [ Designated as safety issue: Yes ]
    Any clinically significant changes in lab values from baseline


Estimated Enrollment: 400
Study Start Date: May 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: December 2015 (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

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01790659

Locations
Panama
Instituto Conmemorativo Gorgas de Estudios de la Salud, Recruiting
Panama City, Panama
Contact: Zeuz Capitan, MSc    507-527-4950    drnsosa@gmail.com   
Contact: Jessica Rodriguez, MSc    507-527-4950      
Principal Investigator: Nestor Sosa, MD         
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

No publications provided

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01790659     History of Changes
Other Study ID Numbers: S-12-21
Study First Received: February 5, 2013
Last Updated: December 17, 2014
Health Authority: United States: Food and Drug Administration
Panama: Ministry of Health
Panama: Commemorative Institute GORGAS of Studies of Health

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
Parasitic Diseases
Protozoan Infections
Skin Diseases
Skin Diseases, Infectious
Skin Diseases, Parasitic
Gentamicins
Paromomycin
Amebicides
Anti-Bacterial Agents
Anti-Infective Agents
Antiparasitic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Synthesis Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on July 05, 2015