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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
110
Paromomycin (20 mg/kg/d) IM for 14 days
AmBisome® (20 mg/kg total dose) IV over 7 days
Miltefosine oral (allometric dosing) for 42 days (arm 1) or 28 days (arm 2)
Prof. Elhassan Centre for tropical Medicine
Doka, Al Qaḑārif, Sudan
RECRUITINGDefinitive 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.
Time frame: 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
Time frame: from start of treatment to 12 month follow-up
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.
Time frame: 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
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.
Time frame: 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.
Time frame: 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.
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Immune Response
To assess the change in immune response during and after end of treatment by measuring cytokines profiles level in the peripheral blood.
Time frame: 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.
Time frame: At screening, day 42 (end of treatment), 3 month follow-up, 6 month follow-up and 12 month follow-up.