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Trial record 35 of 277 for:    Panama

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

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ClinicalTrials.gov Identifier: NCT01790659
Recruitment Status : Completed
First Posted : February 13, 2013
Results First Posted : August 23, 2017
Last Update Posted : February 14, 2018
Sponsor:
Information provided by (Responsible Party):
U.S. Army Medical Research and Development Command

Tracking Information
First Submitted Date  ICMJE February 5, 2013
First Posted Date  ICMJE February 13, 2013
Results First Submitted Date  ICMJE October 11, 2016
Results First Posted Date  ICMJE August 23, 2017
Last Update Posted Date February 14, 2018
Study Start Date  ICMJE May 2013
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 17, 2018)
Percent of Participants With Final 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 ]
The primary efficacy endpoint is percent 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 11, 2013)
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 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.
Change History Complete list of historical versions of study NCT01790659 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2018)
  • Percentage of Subjects With All Lesions Cured [ Time Frame: 100 ± 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 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 ]
    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 Final Clinical Study Report; any inconsistencies can't be changed.
  • 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2013)
  • 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 ]
    • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
    (cure is defined as 100% re-epithelialization of an ulcerated lesion)
  • Median time to initial clinical cure [ Time Frame: to be determined ]
    (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) ]
    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 ]
    Any clinically significant changes in lab values from baseline
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 3 Study of Walter Reed (WR) 279,396 and Paromomycin Alone for the Treatment of Cutaneous Leishmaniasis in Panama
Official Title  ICMJE 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
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Cutaneous Leishmaniasis
Intervention  ICMJE
  • Drug: WR 279,396
    WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%
    Other Name: Paromomycin/Gentamicin topical cream
  • Drug: Paromomycin
    Paromomycin alone
Study Arms  ICMJE
  • Experimental: WR 279,396
    (Paromomycin and Gentamicin Topical Cream)
    Intervention: Drug: WR 279,396
  • Experimental: Paromomycin
    Paromomycin alone
    Intervention: Drug: Paromomycin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 19, 2017)
399
Original Estimated Enrollment  ICMJE
 (submitted: February 11, 2013)
300
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Panama
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01790659
Other Study ID Numbers  ICMJE S-12-21
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party U.S. Army Medical Research and Development Command
Study Sponsor  ICMJE U.S. Army Medical Research and Development Command
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Nestor Sosa, MD, FACP Instituto Conmemorativo Gorgas de Estudios de la Salud
PRS Account U.S. Army Medical Research and Development Command
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP