Phase 3 Study of Walter Reed (WR) 279,396 and Paromomycin Alone for the Treatment of Cutaneous Leishmaniasis in Panama
Information source: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cutaneous Leishmaniasis
Intervention: WR 279,396 (Drug); Paromomycin (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: U.S. Army Medical Research and Materiel Command Official(s) and/or principal investigator(s): Nestor Sosa, MD, FACP, Principal Investigator, Affiliation: Instituto Conmemorativo Gorgas de Estudios de la Salud
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.
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: final clinical cure change from baseline
Secondary outcome: Percentage of subjects with all lesions curedPercentage of all lesions cured at Day 168 (ignores per subject cure rate) Area of ulceration of the index lesion at each measurement time point Area of ulceration all treated lesions at each measurement time point Ulcerated lesion cure rate at each measurement time point Median time to initial clinical cure adverse events (AEs) /serious adverse events (SAEs) (clinical signs and symptoms) Significant lab abnormalities
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
Minimum age: 2 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Instituto Conmemorativo Gorgas de Estudios de la Salud,, Panama City, Panama; Recruiting Zeuz Capitan, MSc, Phone: 507-527-4950, Email: drnsosa@gmail.com Jessica Rodriguez, MSc, Phone: 507-527-4950 Nestor Sosa, MD, Principal Investigator
Additional Information
Starting date: May 2013
Last updated: July 10, 2015
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