Cutaneous LeishmaniasisPhase 3NCT01790659
Phase 3 Study of Walter Reed (WR) 279,396 and Paromomycin Alone for the Treatment of Cutaneous Leishmaniasis in Panama
A Phase 3 study testing WR 279,396 and Paromomycin in people with Cutaneous Leishmaniasis, run by U.S. Army Medical Research and Development Command at 1 site in Panama.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Cutaneous Leishmaniasis
- What is being tested?
- WR 279,396 and Paromomycin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 399 participants
- Where
- 1 sitePanama
- Study dates
- May 2013to Jan 2016
- 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 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Panama1 site
Instituto Conmemorativo Gorgas de Estudios de la Salud,
Panama City
About this study
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
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.
Read the 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.
- Conditions
- Cutaneous Leishmaniasis
- Being tested
- WR 279,396, Paromomycin
- Keywords
- leishmaniasis, cutaneous leishmaniasis, Leishmania panamensis, L panamensis, Paromomycin, Paromomycin/Gentamicin
- Medical subject headings
- Leishmaniasis, Cutaneous, Leishmaniasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WR 279,396Drug
Also called Paromomycin/Gentamicin topical cream
WR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5%
ParomomycinDrug
Paromomycin alone
| Study group | Role | What they receive |
|---|---|---|
| WR 279,396 | Experimental | (Paromomycin and Gentamicin Topical Cream) Receives: Drug: WR 279,396 |
| Paromomycin | Experimental | Paromomycin alone Receives: Drug: Paromomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of Participants With Final Clinical Cure
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.
Measured: 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
Secondary outcomes (5)
Percentage of Subjects With All Lesions Cured
- 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)
Measured: 100 ± 14 days
Percentage of All Lesions Cured at Day 168 (Ignores Per Subject Cure Rate)
Percentage of all lesions meeting criteria for clinical cure during the study at 168 day mark for mITT subjects
Measured: Day 168
Area of Ulceration (mm^2) of the Index Lesion at Each Measurement Time Point
Area of ulceration (mm^2) of the index lesion at each measurement time point for mITT subjects
Measured: 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) All Treated Lesions at Each Measurement Time Point
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.
Measured: 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
Median Time to Initial Clinical Cure for Index Lesions
Median time to initial clinical cure for index lesions (100% re-epithelialization of the index lesion)
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2013 (estimated)
- Study startMay 2013
- Primary completionJan 2016
- Study completionJan 2016
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.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 399 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Nestor Sosa, MD, FACP, Principal investigator, Instituto Conmemorativo Gorgas de Estudios de la Salud
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01790659
- Sponsor's protocol ID
- S-12-21
- Status last verified
- Jan 2018
- First submitted
- 5 Feb 2013
- Last updated
- 14 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01790659
- Acronym / sponsor ID
- S-12-21
- Conditions
- Cutaneous Leishmaniasis
- Keywords
- leishmaniasis, cutaneous leishmaniasis, Leishmania panamensis, L panamensis, Paromomycin, Paromomycin/Gentamicin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 399 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Study start
- May 2013
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 13 Feb 2013 (estimated)
- Results
- Posted 23 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| WR 279,396 | Experimental | Drug: WR 279,396(Paromomycin and Gentamicin Topical Cream) |
| Paromomycin | Experimental | Drug: ParomomycinParomomycin alone |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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
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 279,396Also: Paromomycin/Gentamicin topical creamWR 279,396 is a topical cream of paromomycin 15% and gentamicin 0.5% | Drug | WR 279,396 |
| ParomomycinParomomycin alone | Drug | Paromomycin |
Primary outcome
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.
5 secondary outcomes
Percentage of Subjects With All Lesions Cured
Time frame: 100 ± 14 days
Percentage of All Lesions Cured at Day 168 (Ignores Per Subject Cure Rate)
Time frame: Day 168
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) 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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Nestor Sosa, MD, FACP principal investigator
Instituto Conmemorativo Gorgas de Estudios de la Salud
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 and Paromomycin in people with Cutaneous Leishmaniasis, run by U.S. Army Medical Research and Development Command at 1 site in Panama.
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 7 inclusion and 8 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 Feb 2018. 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 Panama. 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. 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 23 Aug 2017). 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?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Feb 2018.