WR 279, 396 Open Label Treatment Protocol in Tunisia

This study has suspended participant recruitment.
(Study enrollment on temporary hold by sponsor, for administrative reasons)
Sponsor:
Collaborator:
Walter Reed Army Institute of Research (WRAIR)
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT01494350
First received: November 30, 2011
Last updated: February 4, 2013
Last verified: February 2013
  Purpose

The U.S. Army has recently completed a Phase 3 clinical trial in Tunisia. This is an open-label single site trial designed to expand our safety database and capture additional efficacy (final clinical cure rate of an index lesion) of WR 279,396 Topical Cream in Tunisian subjects with non-complicated, non-severe Cutaneous Leishmaniasis (CL). Subjects will be patients who visit Ministry of Health sponsored clinics in Tunisia who present with at least one CL lesion that is ulcerated and amenable to topical treatment. Potential trial subjects will be consented and screened for eligibility including medical history, physical exam, lesion parasitology, and renal and liver function tests. If eligible for the study, subjects will receive WR 279,396 (15% paromomycin + 0.5% gentamicin topical cream) (target n = 110). The cream will be applied topically to all CL lesions once daily for 20 days by an investigator or study nurse. If a subject develops a new lesion during the study, the new lesion may also be treated with the topical cream.


Condition Intervention Phase
Cutaneous Leishmaniasis
Drug: WR 279,396 topical cream
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label Treatment of Non-complicated, Non-severe, Cutaneous Leishmaniasis in Tunisia With WR 279,396 (Paromomycin + Gentamicin Topical Cream) )

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 rate for the index lesion [ Time Frame: Final clincial cure is measured at day 98 ] [ Designated as safety issue: No ]
    Number of index lesions with 100% reepithelialization at Day 98 divided by the total number of index lesions that received any treatment.

  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Adverse events graded 1-4 captured during treatment day 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 ,19 and 20; also on follow up day 28 +/-, 42+/- 4 and 98 +/- 8 days ] [ Designated as safety issue: Yes ]
    Safety endpoints include all AEs including application site reactions graded 1-4 as per the predefined toxicity grading scale in the protocol.


Secondary Outcome Measures:
  • Lesion healing characteristics [ Time Frame: Measured at day 28, 42, and 98 ] [ Designated as safety issue: No ]
    Area of index lesion at each measurement time point.

  • Lesion healing characteristics-early reepithelialization [ Time Frame: Measured at day 28, 42 ] [ Designated as safety issue: No ]
    Proportion of index lesions with 100% reepithelialization at Days 28 and 42.

  • Lesion Healing Characteristics [ Time Frame: Measured at day 28, 42 and 98 ] [ Designated as safety issue: No ]
    Area of all ulcerated lesions at each measurement time point.

  • Lesion Healing characteristics [ Time Frame: Measured at day 98 ] [ Designated as safety issue: No ]
    Final cure rate for all ulcerated lesions (100% reepithelialization for ulcerative lesions) at Day 98

  • Lesion healing characteristics [ Time Frame: Measured at day 98 ] [ Designated as safety issue: No ]
    Loss of all lesion activity for non-ulcerative lesions at Day 98


Estimated Enrollment: 120
Study Start Date: December 2011
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
120 subjects will be enrolled to this open label study to receive WR 279,396 topical cream
Drug: WR 279,396 topical cream
WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin that will be applied to each lesion once a day for 20 days and covered with a sterile gauze and tape dressing.
Other Names:
  • WR 279, 396
  • Topical Paromomycin + Gentamicin Cream

Detailed Description:

Subjects will have an in-clinic follow-up on Days 28 +/- 2 days, 42 +/- 4 days and 98 +/- 8 days to assess safety and cure rates. Safety variables including adverse events (AEs) and serious adverse events (SAEs) will be collected through Day 98. For the primary efficacy evaluation, the index ulcerative lesion will be assessed for clinical response by measurement of the length and width of area of ulceration. All other treated lesions will also be assessed for cure as secondary efficacy endpoints with ulcerated and non-ulcerated lesions being evaluated independently. An ulcerated lesion will be considered to be completely cured if 100% reepithelialization is observed. The length and width of non-ulcerated lesions (nodules, plaques) will also be measured and evaluated for cure (ie, absence of signs of an active lesion). The primary efficacy endpoint is the final clinical cure rate calculated by the number of index lesions that had 100% reepithelialization at Day 98 divided by the total number of index lesions that received at least one topical treatment of WR 279,396.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • At least 18 years of age
  • Subject has a diagnosis of CL in at least one lesion by at least one of the following methods: 1) microscopic identification of amastigotes in stained lesion tissue, or 2) positive culture for promastigotes.
  • Subject has a parasitologically confirmed lesion that satisfies the following criteria for an Index lesion:

    • ulcerative in character
    • lesion size ≥ 1 cm and ≤5 cm (including the area of induration surrounding the lesion)
    • not located on the ear, or on a location that in the opinion of the PI is difficult to maintain application of study drug topically.
  • Subject has < 7 leishmaniasis total lesions.
  • Subject is willing to forego other forms of treatments for CL including other investigational treatments during the study.
  • In the opinion of the investigator, the subject (or their legal guardian) is capable of understanding and complying with the protocol.

Exclusion Criteria:

  • Female with a positive serum pregnancy test or who is breast feeding.
  • History of clinically significant medical problems in the investigator's judgment that might interact, either negatively or positively, with topical treatment of leishmaniasis including any immunocompromising condition.
  • Age adjusted blood creatinine or blood urea nitrogen (BUN) levels indicative of clinically significant renal disease or aspartate amino transferase (AST), alanine amino transferase (ALT), or total bilirubin that suggest clinically significant hepatic impairment as judged by the PI or subinvestigator. Note: This study is designed to evaluate populations who may have some renal or hepatic dysfunction as the drug has not been shown to have serum levels that would be expected to show renal or hepatic toxicity and treatment of the general population presenting with CL is highly desired based on its safety profile compared to other leishmanial drugs.
  • Evidence of disseminated leishmaniasis.
  • Received treatment for leishmaniasis with antimonials or any medication likely, in the opinion of the PI, to modify the course of the Leishmania infection 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: NCT01494350

Locations
Tunisia
Central Clinic-Sidi Bouzid
Tunis, Tunisia
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
Walter Reed Army Institute of Research (WRAIR)
Investigators
Principal Investigator: Afif Ben Salah, M.D., Ph.D. Institute Pasteur Tunisia
  More Information

No publications provided

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01494350     History of Changes
Other Study ID Numbers: S-10-0006; A-16898.3
Study First Received: November 30, 2011
Last Updated: February 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:
cutaneous leishmaniasis
topical treatment
Tunisia

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
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Amebicides
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on July 10, 2014