WR 279,396 Open Label Treatment Protocol in Tunisia

• Sponsor: U.S. Army Medical Research and Development Command (U.S. Fed)
• Overall Status: Terminated
• CT.gov ID: NCT01494350
• Collaborator: Walter Reed Army Institute of Research (WRAIR) (U.S. Fed)
• Enrollment: 50
• Location: 1
• Arm: 1
• Duration (Months): 6
• Patients Per Site Per Month: 8.3

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Cutaneous Leishmaniasis	Drug: WR 279,396 topical cream	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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) )
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: WR 279,396 topical cream 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

Outcome Measures

Primary Outcome Measures

1. Final Clinical Cure Rate for the Index Lesion [Final clincial cure is measured at day 98]

   Number of index lesions with 100% reepithelialization at Day 98.

Secondary Outcome Measures

1. Area of Index Lesions Throughout the Study [Measured at day 0, 20, 28, 42, and 98]

   Area (mm^2) of index lesion on Days 0, 20, 28, 42, and 98.

2. Number of Index Lesions With Reepithelialization Throughout the Study [Measured at day 28 and 42]

   Number of index lesions with 100% reepithelialization on Days 28 and 42.

3. Area of All Ulcerated Lesions Throughout the Study [Measured at day 20, 28, 42 and 98]

   Area of all ulcerated lesions on Days 20, 28, 42, and 98.

4. Number of All Ulcerated Lesions With Reepithelialization on Day 28 [Measured on day 28]

   Final cure rate for all ulcerated lesions (100% reepithelialization for ulcerative lesions) on Day 28

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Central Clinic-Sidi Bouzid	Tunis		Tunisia

Sponsors and Collaborators

• U.S. Army Medical Research and Development Command
• Walter Reed Army Institute of Research (WRAIR)

Investigators

• Principal Investigator: Afif Ben Salah, M.D., Ph.D., Institute Pasteur Tunisia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: U.S. Army Medical Research and Development Command
• ClinicalTrials.gov Identifier: NCT01494350
• Other Study ID Numbers: S-10-0006; A-16898.3
• First Posted: Dec 19, 2011
• Last Update Posted: Dec 19, 2014
• Last Verified: Dec 1, 2014

• Keywords provided by U.S. Army Medical Research and Development Command: cutaneous leishmaniasis; topical treatment; Tunisia
• Additional relevant MeSH terms: Leishmaniasis; Leishmaniasis, Cutaneous; Gentamicins; Paromomycin

Study Results

Participant Flow

Recruitment Details	184 total screened and there were 134 screen failures.

Arm/Group Title	WR 279,396 Topical Cream
Arm/Group Description	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.
Period Title: Overall Study
STARTED	50
COMPLETED	49
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	WR 279,396 Topical Cream
Arm/Group Description	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.
Overall Participants	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.7 (13.1)
Sex: Female, Male (Count of Participants)
Female	30 60%
Male	20 40%
Race/Ethnicity, Customized (participants) [Number]
North African	50 100%
Number of lesions per subject (lesions) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [lesions]	1.96 (1.48)

Outcome Measures

1. Primary Outcome

Title	Final Clinical Cure Rate for the Index Lesion
Description	Number of index lesions with 100% reepithelialization at Day 98.
Time Frame	Final clincial cure is measured at day 98

Outcome Measure Data

Analysis Population Description

modified intent to treat (mITT)

Arm/Group Title	WR 279,396 Topical Cream
Arm/Group Description	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.
Measure Participants	50
Measure index lesions	50
Number [lesions]	48

2. Secondary Outcome

Title	Area of Index Lesions Throughout the Study
Description	Area (mm^2) of index lesion on Days 0, 20, 28, 42, and 98.
Time Frame	Measured at day 0, 20, 28, 42, and 98

Outcome Measure Data

Analysis Population Description

modified intent to treat (mITT). Baseline for this outcome measure does not include one subject (1 index lesion) who withdrew on Day 18.

Arm/Group Title	WR 279,396 Topical Cream
Arm/Group Description	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.
Measure Participants	49
Measure Index lesions	49
Baseline (Day 0)	121 (106)
Day 20	393 (315)
Day 28	203 (238)
Day 42	38.9 (83.2)
Day 98	7.88 (55.1)

3. Secondary Outcome

Title	Number of Index Lesions With Reepithelialization Throughout the Study
Description	Number of index lesions with 100% reepithelialization on Days 28 and 42.
Time Frame	Measured at day 28 and 42

Outcome Measure Data

Analysis Population Description

modified intent to treat (mITT). This outcome measure does not include one subject (2 lesions) who withdrew on Day 18.

Arm/Group Title	WR 279,396 Topical Cream
Arm/Group Description	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.
Measure Participants	49
Measure Index lesions	49
Day 28	8
Day 42	28

4. Secondary Outcome

Title	Area of All Ulcerated Lesions Throughout the Study
Description	Area of all ulcerated lesions on Days 20, 28, 42, and 98.
Time Frame	Measured at day 20, 28, 42 and 98

Outcome Measure Data

Analysis Population Description

modified intent to treat (mITT). Baseline for this outcome measure does not include one subject (2 lesions) who withdrew on Day 18.

Arm/Group Title	WR 279,396 Topical Cream
Arm/Group Description	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.
Measure Participants	49
Measure lesions	96
Baseline (Day 0)	82.6 (90.4)
Day 20	288 (275)
Day 28	149 (198)
Day 42	22.1 (63.3)
Day 98	4.02 (39.4)

5. Secondary Outcome

Title	Number of All Ulcerated Lesions With Reepithelialization on Day 28
Description	Final cure rate for all ulcerated lesions (100% reepithelialization for ulcerative lesions) on Day 28
Time Frame	Measured on day 28

Outcome Measure Data

Analysis Population Description

modified intent to treat (mITT). This outcome measure does not include one subject (2 lesions) who withdrew on Day 18.

Arm/Group Title	WR 279,396 Topical Cream
Arm/Group Description	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.
Measure Participants	49
Measure Lesions	96
Number [lesions]	23

Adverse Events

Time Frame	98 days
Arm/Group Title	WR 279,396 Topical Cream
Arm/Group Description	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.
All Cause Mortality
	WR 279,396 Topical Cream
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	WR 279,396 Topical Cream
	Affected / at Risk (%)	# Events
Total	0/50 (0%)
Other (Not Including Serious) Adverse Events
	WR 279,396 Topical Cream
	Affected / at Risk (%)	# Events
Total	39/50 (78%)
General disorders
Application site erythema	12/50 (24%)
Application site vesicles	27/50 (54%)
Oedema	1/50 (2%)
Pain	1/50 (2%)
Superinfection	1/50 (2%)
Infections and infestations
Bronchitis acute	2/50 (4%)
Injury, poisoning and procedural complications
Scratch	1/50 (2%)
Thermal burn	1/50 (2%)
Investigations
Alanine aminotrasnsferase increased	1/50 (2%)
Blood urea increased	1/50 (2%)
Skin and subcutaneous tissue disorders
Dermatitis contact	10/50 (20%)
Skin irritation	9/50 (18%)

Limitations/Caveats

This study was closed prematurely due study team and travel restrictions but not due to any safety issues with the study subjects. Only a total of 50 of the 110 planned subjects were enrolled in the study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.