Mucosal LeishmaniasisPhase 2NCT06550609
Treatment of Bolivian L Braziliensis Mucosal Leishmaniasis With Inhaled Pentamidine Plus Oral Miltefosine
A Phase 2 study testing Miltefosine Oral Capsule in people with Mucosal Leishmaniasis, run by Fundacion Nacional de Dermatologia at 1 site in Bolivia.
Trial summary
This is a phase 2 study of the combination of inhaled-pentamidine plus oral miltefosine for Bolivian mucosal leishmaniasis. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Mucosal Leishmaniasis
- What is being tested?
- Miltefosine Oral Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteBolivia
- Study dates
- 4 Feb 2025to Feb 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Gender: Male or female
- Age: >12 yrs of age
- Weight: > 45 kg
- Consent: Prior to any investigations
- Mucosal disease: Involvement of the nares, nasal mucosa, palate, pharynx, larynx according to the ENT specialist.
- Parasitology: Parasitological confirmation of the lesion (s) will be made by visualization of Leishmania, culture of Leishmania, or molecular identification of Leishmania (PCR) from the biopsy or aspirate of the lesion (s); or a positive Leishmanin skin test plus a scar characteristic of cutaneous leishmaniasis, plus the epidemiologic antecedent of living now or in the past, in an endemic area.
Who cannot join
- Previous treatment for leishmaniasis: No specific or putatively specific therapy (Sb, pentamidine, amphotericin B, miltefosine, imidazoles, allopurinol) in the last 12 months. Patients may have been previously treated with the agents under investigation---miltefosine, pentamidine---if that treatment ended more than 12 months ago and the disease has not diminished in the last 6 months.
- Other diseases: Concomitant diseases by history that would be likely in the PI's opinion to interact, either positively or negatively, with treatment.
- Laboratory : Values of complete blood count, liver function (AST, ALT, alkaline phosphatase), renal function (creatinine, BUN), pancreatic function (lipase), or uric acid beyond 1.5 x Normal Range and that in the PI's opinion would be clinically meaningful.
- EKG: Clinically significant abnormalities.
- Contraception: Women of childbearing age are required to practice reproductive contraception for 5 months after initiating therapy: abstinence or effective contraception defined as 2 forms of contraception [a barrier method (diaphragm, condom, or cervical cap with spermicidal foam, gel, or cream) plus a 2nd barrier method or hormonal contraceptive or intrauterine device] from day 1 through 5 months post therapy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Bolivia1 site, 1 recruiting
- Recruiting
Hospital de Clinicas
La Paz, La Paz Department, 00000
Sandra Encinas, MD, 76764100
About this study
This is a phase 2 study of the combination of inhaled-pentamidine plus oral miltefosine for Bolivian mucosal leishmaniasis.
Read the detailed description
The 3 major forms of leishmaniasis are visceral, cutaneous, and mucosal disease. Of these, mucosal leishmaniasis (ML) arguably poses the most difficult therapeutic problem. Although visceral disease (VL) occurs in perhaps 300,000 persons a year and is rapidly fatal since TH1 immunity is lacking, visceral disease is well-treated by drugs. Whereras cutaneous disease (CL) is the most prevalent major form occurring in perhaps 1,000,000 persons a year, TH1 Immunity is present and CL self-resolves in 3-18 months.
CL is treated to speed healing of the cutaneous lesion and, for certain species, to try to prevent dissemination of parasites to the oro-nasal mucosa resulting in mucosal leishmaniasis .
Mucosal leishmaniasis (ML) is estimated to occur as a late sequella in approximately 3% of L braziliensis CL. If there are approximately 130,000 cases per year of L braziliensis cutaneous disease, and 3% of these are succeeded by ML, the approximately 4,000 yearly cases of L braziliensis ML makes ML far less common than VL or CL. However, and in spite of more TH1 immunity than cutaneous disease, self-cure of ML is so rare as to be reportable. The patient with ML experiences inexorable erosion of the cartilage of the nose, pharynx, palate, and larynx. ML has been difficult to treat with classical agents (a cure rate of approximately 71%) Thus, of the 3 common forms of leishmaniasis, ML is the form that combines disease severity with poor response to chemotherapy.
Mucosal disease is perhaps the most chemotherapeutically challenging presentation of the leishmaniases. Unlike cutaneous disease, ML results in significant medical morbidity leading to marked psycho-social difficulty, and even mortality. Unlike visceral disease which although mortal quickly responds to therapy, ML is difficult to cure and relapses are common.
Drug combinations are now accepted approaches for many infectious diseases. Since 2 drugs already have the disadvantages of increased cost and potential increased toxicity, use of non-parenteral agents is an important consideration for any proposed combination. As the only recognized oral antileishmanial agent, miltefosine is the drug on which antileishmanial combinations have been based for visceral disease and for cutaneous disease [thermotherapy plus miltefosine: Soto personal communication].
The goal for a miltefosine-based combination for ML would be to raise the ML miltefosine cure rate for "mild" nasal disease to >90% and to raise the miltefosine cure rate for anatomically extensive disease to >58%. Inhaled pentamidine is a non-parenteral agent which in our pilot study was very successful for mild disease (86% cure) but unsuccessful for moderate or severe disease. The combination of oral miltefosine and inhaled pentamidine is a completely non-parenteral regimen that should lead to >90% cure of mild ML disease and could lead to an improved cure rate of moderate-severe disease. Although two drugs will be administered, adverse events should not be additive because miltefosine does not affect the respiratory tract and inhaled pentamidine is minimally absorbed.
This proof-of-concept phase 2 trial will enroll 20 moderate-to-severe ML patients. The primary endpoint is the cure rate for moderate-severe patients in comparison to literature values for miltefosine alone. If mild ML patients present, up to 10 will also be enrolled. The secondary endpoint is demonstrating that the cure rate for mild disease is 90%-100%.
- Conditions
- Mucosal Leishmaniasis
- Being tested
- Miltefosine Oral Capsule
- Keywords
- Leishmaniasis, Mucosal leishmaniasis, Miltefosine, Pentamidine, Combined therapy
- Medical subject headings
- Leishmaniasis, Mucocutaneous, Leishmaniasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Miltefosine Oral CapsuleDrug
Also called Pentamidine isethionate inhaled
Miltefosine 3 pill per day during 28 days AND pentamidine inhaled 300 mg / d during 10 dosis
| Study group | Role | What they receive |
|---|---|---|
| Subjects treated | Experimental | Miltefosine TID for 28 days Inhaled pentamidine 300 mg on days 1,3,5,8,10,12,15,17,19,22 Receives: Drug: Miltefosine Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy
Clinical Score.Qualification compromise in five places (nose skin, nose mucosa, mouh-palate mucosa, pharynx and larynx usind four signs ( erythema, inflamation, infiltration and ulceration) with this scale: 0= absen5t, 1=mild, 2= moderate and 3= severe. Maximun score: 60
Measured: 25 months
Secondary outcomes (1)
Incidence of Treatment-Emergent Adverse Events
as Measured by the Number of Adverse Drug Reactions. Physical examination data will be listed at screening and at follow up time points. For laboratory data, the values that are below the lower limit or above the upper limit of the normal reference range will be flagged. Those values or changes in values, which are identified as being clinically significant, will be flagged and summarized separately. For physical examination data, any clinically relevant changes
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2024
- Study start4 Feb 2025
- Primary completionNov 2027 (estimated)
- Study completionFeb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Mucosal 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
- Not applicable
- Intervention model
- Single group
- Model description
- This proof-of-concept phase 2 trial will enroll 20 moderate-to-severe ML patients. The primary endpoint is the cure rate for moderate-severe patients in comparison to literature values for miltefosine alone. If mild ML patients present, up to 10 will also be enrolled. The secondary endpoint is demonstrating that the cure rate for mild disease is 90%-100%.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundacion Nacional de Dermatologia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jaime Soto, Fundacion Nacional de Dermatologia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06550609
- Sponsor's protocol ID
- ABF-BO-100-10
- Status last verified
- Feb 2025
- First submitted
- 8 Aug 2024
- Last updated
- 26 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cincura C, de Lima CMF, Machado PRL, Oliveira-Filho J, Glesby MJ, Lessa MM, Carvalho EM. Mucosal leishmaniasis: A Retrospective Study of 327 Cases from an Endemic Area of Leishmania (Viannia) braziliensis. Am J Trop Med Hyg. 2017 Sep;97(3):761-766. doi: 10.4269/ajtmh.16-0349. Epub 2017 Jul 19.
PubMed 28722607Piccica M, Lagi F, Bartoloni A, Zammarchi L. Efficacy and safety of pentamidine isethionate for tegumentary and visceral human leishmaniasis: a systematic review. J Travel Med. 2021 Aug 27;28(6):taab065. doi: 10.1093/jtm/taab065.
PubMed 33890115Soto J, Toledo J, Valda L, Balderrama M, Rea I, Parra R, Ardiles J, Soto P, Gomez A, Molleda F, Fuentelsaz C, Anders G, Sindermann H, Engel J, Berman J. Treatment of Bolivian mucosal leishmaniasis with miltefosine. Clin Infect Dis. 2007 Feb 1;44(3):350-6. doi: 10.1086/510588. Epub 2006 Dec 27.
PubMed 17205440Aronson N, Herwaldt BL, Libman M, Pearson R, Lopez-Velez R, Weina P, Carvalho E, Ephros M, Jeronimo S, Magill A. Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Am J Trop Med Hyg. 2017 Jan 11;96(1):24-45. doi: 10.4269/ajtmh.16-84256. Epub 2016 Dec 7. No abstract available.
PubMed 27927991Carvalho JP, Silva SN, Freire ML, Alves LL, Souza CSA, Cota G. The cure rate after different treatments for mucosal leishmaniasis in the Americas: A systematic review. PLoS Negl Trop Dis. 2022 Nov 17;16(11):e0010931. doi: 10.1371/journal.pntd.0010931. eCollection 2022 Nov.
PubMed 36395328
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Bolivian L Braziliensis Mucosal Leishmaniasis With Inhaled Pentamidine Plus Oral Miltefosine
- ClinicalTrials.gov ID
- NCT06550609
- Acronym / sponsor ID
- ABF-BO-100-10
- Conditions
- Mucosal Leishmaniasis
- Keywords
- Leishmaniasis, Mucosal leishmaniasis, Miltefosine, Pentamidine, Combined therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Fundacion Nacional de DermatologiaUniversity, hospital or other
- Study start
- 4 Feb 2025 (actual)
- Primary completion
- Nov 2027 (estimated)
- Study completion
- Feb 2028 (estimated)
- First posted
- 13 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 2 study of the combination of inhaled-pentamidine plus oral miltefosine for Bolivian mucosal leishmaniasis.
Detailed description
The 3 major forms of leishmaniasis are visceral, cutaneous, and mucosal disease. Of these, mucosal leishmaniasis (ML) arguably poses the most difficult therapeutic problem. Although visceral disease (VL) occurs in perhaps 300,000 persons a year and is rapidly fatal since TH1 immunity is lacking, visceral disease is well-treated by drugs. Whereras cutaneous disease (CL) is the most prevalent major form occurring in perhaps 1,000,000 persons a year, TH1 Immunity is present and CL self-resolves in 3-18 months.
CL is treated to speed healing of the cutaneous lesion and, for certain species, to try to prevent dissemination of parasites to the oro-nasal mucosa resulting in mucosal leishmaniasis .
Mucosal leishmaniasis (ML) is estimated to occur as a late sequella in approximately 3% of L braziliensis CL. If there are approximately 130,000 cases per year of L braziliensis cutaneous disease, and 3% of these are succeeded by ML, the approximately 4,000 yearly cases of L braziliensis ML makes ML far less common than VL or CL. However, and in spite of more TH1 immunity than cutaneous disease, self-cure of ML is so rare as to be reportable. The patient with ML experiences inexorable erosion of the cartilage of the nose, pharynx, palate, and larynx. ML has been difficult to treat with classical agents (a cure rate of approximately 71%) Thus, of the 3 common forms of leishmaniasis, ML is the form that combines disease severity with poor response to chemotherapy.
Mucosal disease is perhaps the most chemotherapeutically challenging presentation of the leishmaniases. Unlike cutaneous disease, ML results in significant medical morbidity leading to marked psycho-social difficulty, and even mortality. Unlike visceral disease which although mortal quickly responds to therapy, ML is difficult to cure and relapses are common.
Drug combinations are now accepted approaches for many infectious diseases. Since 2 drugs already have the disadvantages of increased cost and potential increased toxicity, use of non-parenteral agents is an important consideration for any proposed combination. As the only recognized oral antileishmanial agent, miltefosine is the drug on which antileishmanial combinations have been based for visceral disease and for cutaneous disease [thermotherapy plus miltefosine: Soto personal communication].
The goal for a miltefosine-based combination for ML would be to raise the ML miltefosine cure rate for "mild" nasal disease to >90% and to raise the miltefosine cure rate for anatomically extensive disease to >58%. Inhaled pentamidine is a non-parenteral agent which in our pilot study was very successful for mild disease (86% cure) but unsuccessful for moderate or severe disease. The combination of oral miltefosine and inhaled pentamidine is a completely non-parenteral regimen that should lead to >90% cure of mild ML disease and could lead to an improved cure rate of moderate-severe disease. Although two drugs will be administered, adverse events should not be additive because miltefosine does not affect the respiratory tract and inhaled pentamidine is minimally absorbed.
This proof-of-concept phase 2 trial will enroll 20 moderate-to-severe ML patients. The primary endpoint is the cure rate for moderate-severe patients in comparison to literature values for miltefosine alone. If mild ML patients present, up to 10 will also be enrolled. The secondary endpoint is demonstrating that the cure rate for mild disease is 90%-100%.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This proof-of-concept phase 2 trial will enroll 20 moderate-to-severe ML patients. The primary endpoint is the cure rate for moderate-severe patients in comparison to literature values for miltefosine alone. If mild ML patients present, up to 10 will also be enrolled. The secondary endpoint is demonstrating that the cure rate for mild disease is 90%-100%.
| Arm | Type | Receives |
|---|---|---|
| Subjects treated | Experimental | Drug: Miltefosine Oral CapsuleMiltefosine TID for 28 days Inhaled pentamidine 300 mg on days 1,3,5,8,10,12,15,17,19,22 |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Gender: Male or female
- Age: >12 yrs of age
- Weight: > 45 kg
- Consent: Prior to any investigations
- Mucosal disease: Involvement of the nares, nasal mucosa, palate, pharynx, larynx according to the ENT specialist.
Key exclusion criteria (5 listed)
- Previous treatment for leishmaniasis: No specific or putatively specific therapy (Sb, pentamidine, amphotericin B, miltefosine, imidazoles, allopurinol) in the last 12 months. Patients may have been previously treated with the agents under investigation---miltefosine, pentamidine---if that treatment ended more than 12 months ago and the disease has not diminished in the last 6 months.
- Other diseases: Concomitant diseases by history that would be likely in the PI's opinion to interact, either positively or negatively, with treatment.
- Laboratory : Values of complete blood count, liver function (AST, ALT, alkaline phosphatase), renal function (creatinine, BUN), pancreatic function (lipase), or uric acid beyond 1.5 x Normal Range and that in the PI's opinion would be clinically meaningful.
- EKG: Clinically significant abnormalities.
- Contraception: Women of childbearing age are required to practice reproductive contraception for 5 months after initiating therapy: abstinence or effective contraception defined as 2 forms of contraception [a barrier method (diaphragm, condom, or cervical cap with spermicidal foam, gel, or cream) plus a 2nd barrier method or hormonal contraceptive or intrauterine device] from day 1 through 5 months post therapy.
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 |
|---|---|---|
| Miltefosine Oral CapsuleAlso: Pentamidine isethionate inhaledMiltefosine 3 pill per day during 28 days AND pentamidine inhaled 300 mg / d during 10 dosis | Drug | Subjects treated |
Primary outcome
Efficacy
Time frame: 25 months
Clinical Score.Qualification compromise in five places (nose skin, nose mucosa, mouh-palate mucosa, pharynx and larynx usind four signs ( erythema, inflamation, infiltration and ulceration) with this scale: 0= absen5t, 1=mild, 2= moderate and 3= severe. Maximun score: 60
1 secondary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2025.
- Background: PubMed 28722607Cincura C, de Lima CMF, Machado PRL, Oliveira-Filho J, Glesby MJ, Lessa MM, Carvalho EM. Mucosal leishmaniasis: A Retrospective Study of 327 Cases from an Endemic Area of Leishmania (Viannia) braziliensis. Am J Trop Med Hyg. 2017 Sep;97(3):761-766. doi: 10.4269/ajtmh.16-0349. Epub 2017 Jul 19.
- Background: PubMed 33890115Piccica M, Lagi F, Bartoloni A, Zammarchi L. Efficacy and safety of pentamidine isethionate for tegumentary and visceral human leishmaniasis: a systematic review. J Travel Med. 2021 Aug 27;28(6):taab065. doi: 10.1093/jtm/taab065.
- Background: PubMed 17205440Soto J, Toledo J, Valda L, Balderrama M, Rea I, Parra R, Ardiles J, Soto P, Gomez A, Molleda F, Fuentelsaz C, Anders G, Sindermann H, Engel J, Berman J. Treatment of Bolivian mucosal leishmaniasis with miltefosine. Clin Infect Dis. 2007 Feb 1;44(3):350-6. doi: 10.1086/510588. Epub 2006 Dec 27.
- Results publication: PubMed 27927991Aronson N, Herwaldt BL, Libman M, Pearson R, Lopez-Velez R, Weina P, Carvalho E, Ephros M, Jeronimo S, Magill A. Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Am J Trop Med Hyg. 2017 Jan 11;96(1):24-45. doi: 10.4269/ajtmh.16-84256. Epub 2016 Dec 7. No abstract available.
- Results publication: PubMed 36395328Carvalho JP, Silva SN, Freire ML, Alves LL, Souza CSA, Cota G. The cure rate after different treatments for mucosal leishmaniasis in the Americas: A systematic review. PLoS Negl Trop Dis. 2022 Nov 17;16(11):e0010931. doi: 10.1371/journal.pntd.0010931. eCollection 2022 Nov.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Miltefosine Oral Capsule in people with Mucosal Leishmaniasis, run by Fundacion Nacional de Dermatologia at 1 site in Bolivia.
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 6 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 26 Feb 2025. 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 Bolivia. 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 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact jaime soto, MD (75648894, Jasm.dlb@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy (time frame: 25 months). 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 NCT06550609, which also lists 5 linked publications.
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 26 Feb 2025.