Cutaneous LeishmaniasisPhase 2NCT00703924
Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: A Phase 2 Study in the Old World
A Phase 2 study testing WR 279,396 in people with Cutaneous Leishmaniasis, run by U.S. Army Medical Research and Development Command at 2 sites in 2 countries.
Trial summary
This study is to determine the effectiveness and safety of WR 279,396, a topical cream for the treatment of cutaneous leishmaniasis. This study is to be conducted with a placebo control under double-blind conditions in a local population group in Tunisia where leishmaniasis is endemic. Read more about this study
- Who is it for?
- Ages 5 to 75 years
- Conditions the study is for
- Cutaneous Leishmaniasis
- What is being tested?
- WR 279,396
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 92 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Mar 2003to Nov 2005
- Phase
- Phase 2
- 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 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 5-75 years
- Lesions must measure at least 1 cm and be primarily ulcerative
- Have cutaneous leishmaniasis proven parasitologically in the lesion selected for study
- Must have given written informed consent to participate in the study
Who cannot join
- Known drug intolerance to aminoglycosides in the patient or immediate family
- Previous use of antileishmanial drugs (within 3 months) or present use of routinely nephrotoxic or ototoxic drugs
- Patients with tuberculosis under treatment
- Potential for follow-up: have less than 7 months time remaining in present address and/or plan to leave the area for more than 30 days
- Extent of disease: more than 5 lesions or lesion equal to or greater than 5 cm or a lesion less than 5 cm from the eye, or a lesion in the face that, in the opinion of the attending dermatologist could potentially cause significant disfigurement
- Location of disease: mucosal involvement
Show all 14Show fewer
- Disseminated disease: clinically significant lymphadenitis with nodules that are painful and greater than 1 cm in size in the lymphatic drainage of the ulcer
- Concomitant medical problems: significant medical problems of the kidney or liver as determined by history and by the following laboratory studies:
- Hearing abnormality
- Ongoing pregnancy or have plans to become pregnant
- Females of child bearing age (Tunisia Only)
- Signs or symptoms of peripheral neuropathy
- Kidney: clinically significant abnormalities of urine analysis, serum levels of creatinine, BUN, total proteins greater than the upper limit of normal for the laboratory.
- Liver: AST or ALT greater than the upper limit of normal for the laboratory General: glucose, Na+, or K+ greater than the upper limit of normal for the laboratory
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: a Phase 2 Study in the Old World
This study is to determine the effectiveness and safety of WR 279,396, a topical cream for the treatment of cutaneous leishmaniasis. This study is to be conducted with a placebo control under double-blind conditions in a local population group in Tunisia where leishmaniasis is endemic.
Read the detailed description
WR 279,396 is a paromomycin-based topical cream that has shown some suggestion of being effective for the treatment of non-serious, non-complicated cutaneous leishmaniasis in previous clinical studies. The goal of this study is to expand those observations in a larger, more rigorous study to clearly define the efficacy of this product and collect information about adverse effects. Subjects will be randomized to receive either WR 279,396 or vehicle placebo; applied twice a day for 20 days.
- Conditions
- Cutaneous Leishmaniasis
- Being tested
- WR 279,396, Placebo
- Keywords
- cutaneous leishmaniasis topical treatment safety efficacy
- 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 279,396Drug
Also called Paromomycin topical cream
A topical cream containing 15% paromomycin and 0.5% gentamicin. Approximately 0.0005 mL per mm2 of skin lesion
PlaceboDrug
Also called Topical vehicle placebo
Topical cream vehicle. Approximately 0.0005 mL per mm2 of skin lesion
| Study group | Role | What they receive |
|---|---|---|
| WR 279,396 | Experimental | WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin Receives: Drug: WR 279,396 |
| Placebo | Placebo comparator | Topical cream vehicle containing all of the components in WR 279,396 except the active ingredients. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Clinical Response (CCR) of Lesion at Days 50, 100 and 180 (+7 Days)
CCR is defined as at least 50% reduction, from baseline, in index lesion area of ulceration at study days 50, 100 and 180 (+ 7 days). Randomized subjects were compared using the uncorrected Fisher's exact test. Confidence intervals (95%) were constructed on the difference between the two group proportions. The log-rank test was used to compare the time to complete re-epithelialization of the index lesion without relapse. Cure of all subjects lesions was also compared using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable. The Breslow-Day test was used to examine whether the effect of WR 279,396 varied between subgroups
Measured: 180 days
Safety of WR 279,396 (AEs and SAEs)
Safety was evaluated on each day during daily administration of the topical products. Subjects were observed and questioned for the occurrence of solicited local side effects (eg, pain, erythema, edema) and solicited systemic side effects (eg, vertigo, tinnitus, diminished hearing). Non-solicited AE evaluations included spontaneous reports from subjects and clinical observations.
Measured: 180 days
Secondary outcomes (3)
Time to Complete Re-epithelialization of the Index Lesion Ulcer Without Relapse
100% re-epithelialization of the index lesion without having had a relapse. The log-rank test was used to compare the time to complete re-epithelialization.
Measured: 180 days
Final Cure Rate by Subject of All Lesions
Final cure rate by subject was determined using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable.
Measured: 180 days
Rate of Relapse
Relapse is defined as enlargement of the index lesion compared to previous measurement at any time after day 50 (+ 7 days) or not demonstrating CCR by study day 180. CCR was compared using uncorrected Fisher's exact test.
Confidence intervals (95%) were constructed on the difference between the two group proportions. The log-rank test was used to compare the time to complete re-epithelialization of the index lesion without relapse. Cure of all subjects lesions was also compared using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable.
Measured: 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2008 (estimated)
- Study startMar 2003
- Primary completionNov 2004
- Study completionNov 2005
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- U.S. Army Medical Research and Development Command
- Sponsor type
- US federal agency
- Collaborators
- Walter Reed Army Institute of Research (WRAIR)
- Responsible party
- Sponsor
- Investigators
- Afif Ben Salah, M.D., Ph.D., Principal investigator, Institute Pasteur Tunisia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00703924
- Sponsor's protocol ID
- A-9768.1
- Other IDs
- IND 50098
- Status last verified
- Apr 2017
- First submitted
- 20 Jun 2008
- Last updated
- 30 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Data will be shared with WRAIR
Publications
Ben Salah A, Buffet PA, Morizot G, Ben Massoud N, Zaatour A, Ben Alaya N, Haj Hamida NB, El Ahmadi Z, Downs MT, Smith PL, Dellagi K, Grogl M. WR279,396, a third generation aminoglycoside ointment for the treatment of Leishmania major cutaneous leishmaniasis: a phase 2, randomized, double blind, placebo controlled study. PLoS Negl Trop Dis. 2009;3(5):e432. doi: 10.1371/journal.pntd.0000432. Epub 2009 May 5.
PubMed 19415122
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Topical Treatment of Cutaneous Leishmaniasis With WR 279,396: a Phase 2 Study in the Old World
- ClinicalTrials.gov ID
- NCT00703924
- Acronym / sponsor ID
- A-9768.1
- Conditions
- Cutaneous Leishmaniasis
- Keywords
- cutaneous leishmaniasis topical treatment safety efficacy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- U.S. Army Medical Research and Development CommandUS federal agency
- Collaborators
- Walter Reed Army Institute of Research (WRAIR)
- Study start
- Mar 2003
- Primary completion
- Nov 2004 (actual)
- Study completion
- Nov 2005 (actual)
- First posted
- 24 Jun 2008 (estimated)
- Results
- Posted 15 Feb 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 to determine the effectiveness and safety of WR 279,396, a topical cream for the treatment of cutaneous leishmaniasis. This study is to be conducted with a placebo control under double-blind conditions in a local population group in Tunisia where leishmaniasis is endemic.
Detailed description
WR 279,396 is a paromomycin-based topical cream that has shown some suggestion of being effective for the treatment of non-serious, non-complicated cutaneous leishmaniasis in previous clinical studies. The goal of this study is to expand those observations in a larger, more rigorous study to clearly define the efficacy of this product and collect information about adverse effects. Subjects will be randomized to receive either WR 279,396 or vehicle placebo; applied twice a day for 20 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| WR 279,396 | Experimental | Drug: WR 279,396WR 279,396 is a topical antibiotic cream containing paromomycin and gentamicin |
| Placebo | Placebo comparator | Drug: PlaceboTopical cream vehicle containing all of the components in WR 279,396 except the active ingredients. |
Who may qualify
- Ages
- 5 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Age 5-75 years
- Lesions must measure at least 1 cm and be primarily ulcerative
- Have cutaneous leishmaniasis proven parasitologically in the lesion selected for study
- Must have given written informed consent to participate in the study
Key exclusion criteria (14 listed)
- Known drug intolerance to aminoglycosides in the patient or immediate family
- Previous use of antileishmanial drugs (within 3 months) or present use of routinely nephrotoxic or ototoxic drugs
- Patients with tuberculosis under treatment
- Potential for follow-up: have less than 7 months time remaining in present address and/or plan to leave the area for more than 30 days
- Extent of disease: more than 5 lesions or lesion equal to or greater than 5 cm or a lesion less than 5 cm from the eye, or a lesion in the face that, in the opinion of the attending dermatologist could potentially cause significant disfigurement
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 topical creamA topical cream containing 15% paromomycin and 0.5% gentamicin. Approximately 0.0005 mL per mm2 of skin lesion | Drug | WR 279,396 |
| PlaceboAlso: Topical vehicle placeboTopical cream vehicle. Approximately 0.0005 mL per mm2 of skin lesion | Drug | Placebo |
Primary outcome
Complete Clinical Response (CCR) of Lesion at Days 50, 100 and 180 (+7 Days)
Time frame: 180 days
CCR is defined as at least 50% reduction, from baseline, in index lesion area of ulceration at study days 50, 100 and 180 (+ 7 days). Randomized subjects were compared using the uncorrected Fisher's exact test. Confidence intervals (95%) were constructed on the difference between the two group proportions. The log-rank test was used to compare the time to complete re-epithelialization of the index lesion without relapse. Cure of all subjects lesions was also compared using the Fisher's exact test. To adjust for baseline differences in the treatment groups, a linear model for the proportion of subjects achieving CCR was fit for each baseline variable of interest with covariates for treatment group and the baseline variable. The Breslow-Day test was used to examine whether the effect of WR 279,396 varied between subgroups
Safety of WR 279,396 (AEs and SAEs)
Time frame: 180 days
Safety was evaluated on each day during daily administration of the topical products. Subjects were observed and questioned for the occurrence of solicited local side effects (eg, pain, erythema, edema) and solicited systemic side effects (eg, vertigo, tinnitus, diminished hearing). Non-solicited AE evaluations included spontaneous reports from subjects and clinical observations.
3 secondary outcomes
Time to Complete Re-epithelialization of the Index Lesion Ulcer Without Relapse
Time frame: 180 days
Final Cure Rate by Subject of All Lesions
Time frame: 180 days
Rate of Relapse
Time frame: 180 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19415122Ben Salah A, Buffet PA, Morizot G, Ben Massoud N, Zaatour A, Ben Alaya N, Haj Hamida NB, El Ahmadi Z, Downs MT, Smith PL, Dellagi K, Grogl M. WR279,396, a third generation aminoglycoside ointment for the treatment of Leishmania major cutaneous leishmaniasis: a phase 2, randomized, double blind, placebo controlled study. PLoS Negl Trop Dis. 2009;3(5):e432. doi: 10.1371/journal.pntd.0000432. Epub 2009 May 5.
- Individual participant dataSharing planned: Yes. Data will be shared with WRAIR
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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
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing WR 279,396 in people with Cutaneous Leishmaniasis, run by U.S. Army Medical Research and Development Command at 2 sites in 2 countries.
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 4 inclusion and 14 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 30 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France, 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 15 Feb 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?
Complete Clinical Response (CCR) of Lesion at Days 50, 100 and 180 (+7 Days) (time frame: 180 days). The study lists 2 primary outcomes in all. 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 NCT00703924, 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 30 May 2017.