Cutaneous LeishmaniasisPhase 3NCT00606580
Phase 3 Study to Evaluate WR 279,396 vs. Paromomycin Alone to Treat Cutaneous Leishmaniasis (in Tunisia)
A Phase 3 study testing WR 279,396 topical cream and Paromomycin Alone topical cream in people with Cutaneous Leishmaniasis, run by U.S. Army Medical Research and Development Command at 1 site in Tunisia.
Trial summary
This study will test the ability of the topical cream WR 279,396 to treat the skin lesions caused by the parasite called leishmania. WR 279,396 is an antibiotic preparation that contains paromomycin + gentamicin. Read more about this study
- Who is it for?
- Ages 5 to 65 years
- Conditions the study is for
- Cutaneous Leishmaniasis
- What is being tested?
- WR 279,396 topical cream and Paromomycin Alone topical cream
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 375 participants
- Where
- 1 siteTunisia
- Study dates
- Jan 2008to Jul 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The subject was age 5 years or older, but less than 65 years.
- The subject was able to understand the information provided to him/her and give written informed consent. Consent was obtained from the parent/guardian of subjects who were < 18 years old. Children 12 to < 18 years old were asked to sign the written assent form. Witnessed verbal assent was obtained from subjects 5 to 11 years old.
- The subject was a male or female who was generally healthy.
- The subject had cutaneous lesions diagnosed as leishmaniasis in the index lesion by: (1) the identification of promastigotes in a culture of an aspirated lesion, or (2) the microscopic identification of Leishmania amastigotes on a DifQuik or Giemsa stained smear obtained from a lesion scraping.
- The subject had five or fewer cutaneous lesions.
- The subject had one lesion, which would be designated as the index lesion, that was ≥ 1 and < 5 cm in its greatest diameter and primarily ulcerative, ie, not purely verrucous or nodular.
- The subject was willing to forego other forms of treatment for CL, including other investigational treatment during the study.
- In the opinion of the principal investigator, the subject or subject's parent/guardian was capable of understanding and complying with the protocol
Who cannot join
- The subject received previous treatment for leishmaniasis (including WR 279,396) within the last 6-months, with the exception of mercurochrome.
- The subject had difficulty complying with instructions on maintaining the dressing, eg, due to life style activities or age.
- The subject had only a single lesion whose characteristics included any of the following: verrucous or nodular lesion, ≥ 5 cm in its greatest diameter, < 1 cm or located on the ear, or other location that in the opinion of the principal investigator would be difficult to maintain application of study drug topically.
- The subject had a lesion due to Leishmania that involved the mucosa.
- The subject had signs or symptoms of disseminated disease, ie, clinically significant lymphadenitis with nodules that were painful and > 1 cm in the lymphatic drainage of the ulcer.
- The subject was a female with a positive urine pregnancy test, or who was breast feeding or lactating.
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- The subject had an active malignancy or had a history of a solid, metastatic or hematologic malignancy, with the exception of a basal or squamous cell carcinoma of the skin that had been removed.
- The subject had a significant organ abnormality or chronic disease that, in the opinion of the investigator, would warrant exclusion of the subject from the study or would prevent the subject from completing the study.
- The subject was receiving any of the following medications: any medication containing pentavalent antimony, including stibogluconate sodium (Pentostam®) and meglumine antimoniate (Glucantime®); amphotericin B, including liposomal amphotericin B and amphotericin B deoxycholate; other medications containing paromomycin (administered IV or topically); methylbenzethonium chloride, fluconazole, ketoconazole, itraconazole; pentamidine; or allopurinol.
- The subject or the subject's parent/guardian was unable to understand verbal and/or written Arabic, English, or French (languages in which certified translations of the informed consent were available).
- The subject presented with an immuno-compromising condition, including recidivant leishmaniasis (during the past 2 years), or diabetes.
- The subject had a history of known or suspected idiosyncratic reactions or hypersensitivity to aminoglycosides.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pivotal, Randomized, Double-blind, Vehicle-controlled Study to Evaluate WR 279,396 and Paromomycin Alone to Treat Cutaneous Leishmaniasis (in Tunisia)
This study will test the ability of the topical cream WR 279,396 to treat the skin lesions caused by the parasite called leishmania. WR 279,396 is an antibiotic preparation that contains paromomycin + gentamicin. This cream will be compared to the effect of a topical cream containing paromomycin alone and to a placebo cream that contains no antibiotics. Therefore, this study will have three groups of patients, and they will be assigned to one of these treatments randomly. The study will be carried out without the patient or the physician knowing which cream is being used for which patient. The goal is to determine if WR 279,396 cream or the paromomycin cream is better than placebo, and if WR 279,396 is better than paromomycin alone.
Read the detailed description
This is an efficacy study to test the ability of WR 279,396 topical cream to treat uncomplicated cutaneous leishmaniasis caused primarily by Leishmania major in adults and children in Tunisia where the disease in endemic. A total of 375 volunteers will be randomized to the three arms described above to determine product efficacy. Safety data in all three arms will also be collected.
- Conditions
- Cutaneous Leishmaniasis
- Being tested
- WR 279,396 topical cream, Paromomycin Alone topical cream, Vehicle placebo cream
- Keywords
- cutaneous leishmaniasis, topical treatment, Tunisia
- Medical subject headings
- Leishmaniasis, Cutaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WR 279,396 topical creamDrug
WR 279,396 is a topical antibiotic cream containing 15% paromomycin and 0.5% gentamicin that will be applied to each lesion once a day and covered with a sterile gauze and tape dressing.
Paromomycin Alone topical creamDrug
The antibiotic paromomycin 15% in the same topical cream used in arm 1 will be applied to lesions daily and covered with a protective sterile gauze and tape dressing.
Vehicle placebo creamDrug
Applied daily to cutaneous leishmaniasis lesions, primarily ulcerative, and covered with a protective, sterile gauze and tape dressing.
| Study group | Role | What they receive |
|---|---|---|
| WR 279,396 Topical Treament | Experimental | WR 279,396 topical cream (15% paromomycin + 0.5% gentamicin topical cream) Receives: Drug: WR 279,396 topical cream |
| Paromomycin Alone Topical treatment | Experimental | Paromomycin Alone topical cream (15% paromomycin topical cream) Receives: Drug: Paromomycin Alone topical cream |
| Vehicle Placebo Cream | Placebo comparator | The cream base without the addition of paromomycin or gentamicin Receives: Drug: Vehicle placebo cream |
What is being measured
The primary outcome is the main question the study is designed to answer.
Final Clinical Cure Rate
Final clinical cure was defined as an index lesion that met the criteria for initial clinical cure without relapse. Definitions for index lesion outcomes were as follows:
- Initial Clinical Improvement: At least 50% to 99% reduction in the size of the measured lesion from the baseline measurement by the Day 42 evaluation.
- Initial Clinical Cure: 100% re-epithelialization (ie, a 0 x 0 length x width measurement) of the lesion at the nominal Day 42 evaluation, or initial clinical improvement followed by 100% re-epithelialization by Day 98.
- Relapse: Initial clinical cure followed by re-ulceration by Day 168, or initial clinical improvement followed by lesion enlargement by Day 168.
- Final Clinical Cure: Initial clinical cure without relapse through study Day 168.Clinical Failure: Lack of at least initial clinical improvement by Day 42, or relapse.
Measured: Day 42, 98, and 168
Secondary outcomes (11)
Final Clinical Cure Rate (Per Protocol Dataset)
Final clinical cure was defined as an index lesion that met the criteria for initial clinical cure without relapse. Definitions for index lesion outcomes as described in the primary outcome measure.
Measured: Day 42, 98, and 168
Estimated Percentage Subjects With Re-epithelialization of the Index Lesion Without Relapse
For the first of the above analyses, subjects were considered to have endpoint events at the first assessment on or before Day 42 where complete re-epithelialization occurred at the index lesion that was not followed by a later assessment where ulceration was present. Subjects who did not have complete re-epithelialization by Day 42 or who relapsed after Day 42 were censored in the analysis at the Day 42 assessment. This analysis was only to be conducted through Day 42.
Measured: Day 42
Estimated Percentage of Subjects With Re-epithelialization of the Index Lesion Without Relapse at Various Times of Follow-up
Measured: Days 42, 49, and 98
Estimated Percentage of All Treated Ulcerated Lesions Without Relapse at Day 42
Measured: Days 42
Estimated Percentage of All Treated Ulcerated Lesions Without Relapse at Day 49
Measured: Days 49
Estimated Percentage of All Treated Ulcerated Lesions Without Relapse at Day 98
Measured: Days 98
Number of Subjects Achieving Initial Clinical Improvement of the Index Lesion
Measured: Day 42
Number of Subjects Achieving Re-epithelialization of the Index Lesion Without Relapse
Number of Subjects Achieving Re-epithelialization of the Index Lesion by Day 42 without Relapse from Day 42 Onward, Imputing Relapse for any Subject with a Missing Visit after Day 42
Measured: Day 168
Number of Subjects Achieving Re-epithelialization of All Treated Ulcerated Lesions Without Subsequent Relapse
Number of Subjects Achieving Re-epithelialization of All Treated Ulcerated Lesions at Day 42 without Subsequent Relapse from Day 42 Onward,
Measured: Day 168
Number of All Ulcerated Lesions Achieving 100% Re-epithelialization by Day 42
Measured: Day 42
Number of Subjects With a Relapse on or After Day 42
Measured: Day 168
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2008 (estimated)
- Study startJan 2008
- Primary completionJul 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cutaneous LeishmaniasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 375 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Afif Ben Salah, M.D., Ph.D., Principal investigator, Institute Pasteur Tunisia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00606580
- Sponsor's protocol ID
- A-14134
- Status last verified
- Jun 2014
- First submitted
- 21 Jan 2008
- Last updated
- 14 Jul 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ben Salah A, Ben Messaoud N, Guedri E, Zaatour A, Ben Alaya N, Bettaieb J, Gharbi A, Belhadj Hamida N, Boukthir A, Chlif S, Abdelhamid K, El Ahmadi Z, Louzir H, Mokni M, Morizot G, Buffet P, Smith PL, Kopydlowski KM, Kreishman-Deitrick M, Smith KS, Nielsen CJ, Ullman DR, Norwood JA, Thorne GD, McCarthy WF, Adams RC, Rice RM, Tang D, Berman J, Ransom J, Magill AJ, Grogl M. Topical paromomycin with or without gentamicin for cutaneous leishmaniasis. N Engl J Med. 2013 Feb 7;368(6):524-32. doi: 10.1056/NEJMoa1202657.
PubMed 23388004
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pivotal, Randomized, Double-blind, Vehicle-controlled Study to Evaluate WR 279,396 and Paromomycin Alone to Treat Cutaneous Leishmaniasis (in Tunisia)
- ClinicalTrials.gov ID
- NCT00606580
- Acronym / sponsor ID
- A-14134
- Conditions
- Cutaneous Leishmaniasis
- Keywords
- cutaneous leishmaniasis, topical treatment, Tunisia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 375 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Study start
- Jan 2008
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 4 Feb 2008 (estimated)
- Results
- Posted 14 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test the ability of the topical cream WR 279,396 to treat the skin lesions caused by the parasite called leishmania. WR 279,396 is an antibiotic preparation that contains paromomycin + gentamicin. This cream will be compared to the effect of a topical cream containing paromomycin alone and to a placebo cream that contains no antibiotics. Therefore, this study will have three groups of patients, and they will be assigned to one of these treatments randomly. The study will be carried out without the patient or the physician knowing which cream is being used for which patient. The goal is to determine if WR 279,396 cream or the paromomycin cream is better than placebo, and if WR 279,396 is better than paromomycin alone.
Detailed description
This is an efficacy study to test the ability of WR 279,396 topical cream to treat uncomplicated cutaneous leishmaniasis caused primarily by Leishmania major in adults and children in Tunisia where the disease in endemic. A total of 375 volunteers will be randomized to the three arms described above to determine product efficacy. Safety data in all three arms will also be collected.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| WR 279,396 Topical Treament | Experimental | Drug: WR 279,396 topical creamWR 279,396 topical cream (15% paromomycin + 0.5% gentamicin topical cream) |
| Paromomycin Alone Topical treatment | Experimental | Drug: Paromomycin Alone topical creamParomomycin Alone topical cream (15% paromomycin topical cream) |
| Vehicle Placebo Cream | Placebo comparator | Drug: Vehicle placebo creamThe cream base without the addition of paromomycin or gentamicin |
Who may qualify
- Ages
- 5 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- The subject was age 5 years or older, but less than 65 years.
- The subject was able to understand the information provided to him/her and give written informed consent. Consent was obtained from the parent/guardian of subjects who were < 18 years old. Children 12 to < 18 years old were asked to sign the written assent form. Witnessed verbal assent was obtained from subjects 5 to 11 years old.
- The subject was a male or female who was generally healthy.
- The subject had cutaneous lesions diagnosed as leishmaniasis in the index lesion by: (1) the identification of promastigotes in a culture of an aspirated lesion, or (2) the microscopic identification of Leishmania amastigotes on a DifQuik or Giemsa stained smear obtained from a lesion scraping.
- The subject had five or fewer cutaneous lesions.
Key exclusion criteria (12 listed)
- The subject received previous treatment for leishmaniasis (including WR 279,396) within the last 6-months, with the exception of mercurochrome.
- The subject had difficulty complying with instructions on maintaining the dressing, eg, due to life style activities or age.
- The subject had only a single lesion whose characteristics included any of the following: verrucous or nodular lesion, ≥ 5 cm in its greatest diameter, < 1 cm or located on the ear, or other location that in the opinion of the principal investigator would be difficult to maintain application of study drug topically.
- The subject had a lesion due to Leishmania that involved the mucosa.
- The subject had signs or symptoms of disseminated disease, ie, clinically significant lymphadenitis with nodules that were painful and > 1 cm in the lymphatic drainage of the ulcer.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| WR 279,396 topical creamWR 279,396 is a topical antibiotic cream containing 15% paromomycin and 0.5% gentamicin that will be applied to each lesion once a day and covered with a sterile gauze and tape dressing. | Drug | WR 279,396 Topical Treament |
| Paromomycin Alone topical creamThe antibiotic paromomycin 15% in the same topical cream used in arm 1 will be applied to lesions daily and covered with a protective sterile gauze and tape dressing. | Drug | Paromomycin Alone Topical treatment |
| Vehicle placebo creamApplied daily to cutaneous leishmaniasis lesions, primarily ulcerative, and covered with a protective, sterile gauze and tape dressing. | Drug | Vehicle Placebo Cream |
Primary outcome
Final Clinical Cure Rate
Time frame: Day 42, 98, and 168
Final clinical cure was defined as an index lesion that met the criteria for initial clinical cure without relapse. Definitions for index lesion outcomes were as follows: * Initial Clinical Improvement: At least 50% to 99% reduction in the size of the measured lesion from the baseline measurement by the Day 42 evaluation. * Initial Clinical Cure: 100% re-epithelialization (ie, a 0 x 0 length x width measurement) of the lesion at the nominal Day 42 evaluation, or initial clinical improvement followed by 100% re-epithelialization by Day 98. * Relapse: Initial clinical cure followed by re-ulceration by Day 168, or initial clinical improvement followed by lesion enlargement by Day 168. * Final Clinical Cure: Initial clinical cure without relapse through study Day 168.Clinical Failure: Lack of at least initial clinical improvement by Day 42, or relapse.
11 secondary outcomes
Final Clinical Cure Rate (Per Protocol Dataset)
Time frame: Day 42, 98, and 168
Estimated Percentage Subjects With Re-epithelialization of the Index Lesion Without Relapse
Time frame: Day 42
Estimated Percentage of Subjects With Re-epithelialization of the Index Lesion Without Relapse at Various Times of Follow-up
Time frame: Days 42, 49, and 98
Estimated Percentage of All Treated Ulcerated Lesions Without Relapse at Day 42
Time frame: Days 42
Estimated Percentage of All Treated Ulcerated Lesions Without Relapse at Day 49
Time frame: Days 49
Estimated Percentage of All Treated Ulcerated Lesions Without Relapse at Day 98
Time frame: Days 98
Number of Subjects Achieving Initial Clinical Improvement of the Index Lesion
Time frame: Day 42
Number of Subjects Achieving Re-epithelialization of the Index Lesion Without Relapse
Time frame: Day 168
Number of Subjects Achieving Re-epithelialization of All Treated Ulcerated Lesions Without Subsequent Relapse
Time frame: Day 168
Number of All Ulcerated Lesions Achieving 100% Re-epithelialization by Day 42
Time frame: Day 42
Number of Subjects With a Relapse on or After Day 42
Time frame: Day 168
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23388004Ben Salah A, Ben Messaoud N, Guedri E, Zaatour A, Ben Alaya N, Bettaieb J, Gharbi A, Belhadj Hamida N, Boukthir A, Chlif S, Abdelhamid K, El Ahmadi Z, Louzir H, Mokni M, Morizot G, Buffet P, Smith PL, Kopydlowski KM, Kreishman-Deitrick M, Smith KS, Nielsen CJ, Ullman DR, Norwood JA, Thorne GD, McCarthy WF, Adams RC, Rice RM, Tang D, Berman J, Ransom J, Magill AJ, Grogl M. Topical paromomycin with or without gentamicin for cutaneous leishmaniasis. N Engl J Med. 2013 Feb 7;368(6):524-32. doi: 10.1056/NEJMoa1202657.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Afif Ben Salah, M.D., Ph.D. principal investigator
Institute Pasteur Tunisia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing WR 279,396 topical cream and Paromomycin Alone topical cream in people with Cutaneous Leishmaniasis, run by U.S. Army Medical Research and Development Command at 1 site in Tunisia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Tunisia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jul 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Final Clinical Cure Rate (time frame: Day 42, 98, and 168). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00606580, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2014.