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This is an open label, randomized non comparative phase II clinical trial conducted on parallel groups, to assess the safety and efficacy of the combination of Paromomycin (20 mg/kg/d) IM for 14 days and Miltefosine (allometric dosing) oral for 42 days, and a combination of AmBisome® (20 mg/kg total dose) IV over 7 days and Miltefosine oral for 28 days (allometric dosing) for the treatment of PKDL patients in Sudan.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1: Paromomycin + Miltefosine | Experimental | Paromomycin 20 mg/kg/d IM for 14 days combined with Miltefosine allometric BID PO dosing for 42 days |
|
| Arm 2: Ambisome + Miltefosine | Experimental | AmBisome® 5mg/kg/d IV infusion at D1, D3, D5 and D7 (20 mg/kg total dose) combined with Miltefosine allometric BID PO dosing for 28 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Paromomycin | Drug | Paromomycin (20 mg/kg/d) IM for 14 days |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Definitive Cure | definitive cure at 12 months after treatment onset, defined as clinical cure (100% lesions resolution) and no additional PKDL treatment between end of therapy and 12 months follow-up assessment. | 12 months follow-up assessment |
| Incidence of treatment-emergent adverse events | Frequency of SAE from start of treatment to 12 months follow-up Frequency and severity of all adverse events Frequency and severity of adverse events that lead to treatment discontinuation | from start of treatment to 12 month follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics of Miltefosine | To assess the maximal accumulation (Cmax) of Miltefosine in the skin at the end of treatment and correlate it with achieved plasma concentrations. | Miltefosine concentration in the skin will be measured at day 14 and day 42 for MF+PM arm and at day 7 and day 28 for Ambisome+MF arm. Miltefosine concentration in the blood will be measured at day 1, day 7, day 14, day 28, day 42 and 3 month |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Gina M Ouattara, manager | Contact | +254 20 3995000 | gmouattara@dndi.org | |
| Severine Monnerat, coordinator | Contact | +41 22 907 7891 | smonnerat@dndi.org |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Prof. Elhassan Centre for tropical Medicine | Recruiting | Doka | Al Qaḑārif | Sudan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39007942 | Derived | Torres A, Younis BM, Alamin M, Tesema S, Bernardo L, Solana JC, Moreno J, Mustafa AA, Alves F, Musa AM, Carrillo E. Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome. J Epidemiol Glob Health. 2024 Sep;14(3):1167-1179. doi: 10.1007/s44197-024-00270-0. Epub 2024 Jul 15. | |
| 37988402 |
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| ID | Term |
|---|---|
| D010303 | Paromomycin |
| C068538 | liposomal amphotericin B |
| C039128 | miltefosine |
| ID | Term |
|---|---|
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
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| Ambisome |
| Drug |
AmBisome® (20 mg/kg total dose) IV over 7 days |
|
|
| Miltefosine | Drug | Miltefosine oral (allometric dosing) for 42 days (arm 1) or 28 days (arm 2) |
|
|
| Pharmacokinetics of Amphotericin B (MF + Ambisome arm only) | To assess the maximal accumulation (Cmax) of Amphotericin B in the skin at the end of treatment and correlate it with achieved plasma concentrations. | Amphotericin B concentration will be measured in the skin at day 7 and day 28. Amphotericin B concentration in the blood will be measured at day 1 and day 7. |
| Pharmacokinetics of Paromomycin (MF + Paromomycin arm only) | To assess the maximal accumulation (Cmax) of Paromomycin in the skin at the end of treatment and correlate it with achieved plasma concentrations. | Paromomycin concentration will be measured in the skin at day 14 and day 42. Paromomycin concentration in the blood will be measured at day 1 and day 14. |
| Immune Response | To assess the change in immune response during and after end of treatment by measuring cytokines profiles level in the peripheral blood. | At screening, at day 42 (end of treatment) and at 6 month follow-up |
| Parasite quantification in blood and skin | Parasites will be quantified in blood and skin, by microscopy and qPCR, to assess the clearance before and after treatment. | At screening, day 42 (end of treatment), 3 month follow-up, 6 month follow-up and 12 month follow-up. |
| Derived |
| Younis BM, Mudawi Musa A, Monnerat S, Abdelrahim Saeed M, Awad Gasim Khalil E, Elbashir Ahmed A, Ahmed Ali M, Noureldin A, Muthoni Ouattara G, Nyakaya GM, Teshome S, Omollo T, Ochieng M, Egondi T, Mmbone M, Chu WY, Dorlo TPC, Zijlstra EE, Wasunna M, Alvar J, Alves F. Safety and efficacy of paromomycin/miltefosine/liposomal amphotericin B combinations for the treatment of post-kala-azar dermal leishmaniasis in Sudan: A phase II, open label, randomized, parallel arm study. PLoS Negl Trop Dis. 2023 Nov 21;17(11):e0011780. doi: 10.1371/journal.pntd.0011780. eCollection 2023 Nov. |