PKDL - Post-Kala-Azar Dermal Leishmanioid Clinical Trial
Official title:
An Open Label, Randomized, Parallel Arm Clinical Trial of Two Regimens to Assess the Safety and Efficacy for Treatment of Post Kala-azar Dermal Leishmaniasis (PKDL) Patients in Sudan
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.
| Status | Recruiting |
| Enrollment | 110 |
| Est. completion date | May 1, 2022 |
| Est. primary completion date | May 9, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 6 Years to 60 Years |
| Eligibility |
Inclusion Criteria: - Confirmed PKDL case by clinical presentation and demonstration of parasites by microscopy in a skin smear or by PCR, with documented stable or progressive disease for at least 6 months or grade 3 PKDL - Male or Female patients aged 6 to 60 years - Written voluntarily informed consent is obtained from the patient, or his guardian if the patient is < 18 years old. In the case of minors aged >12 to <18, assent from the children is also needed in addition to the guardian's consent. Exclusion Criteria: - Patients who had prior treatment of PKDL within the last 1 year - Pregnant and lactating women and women of childbearing age (12 to 55 years) who do not accept to have a pregnancy test and who do not agree to use contraception during treatment period and for 5 months after the end of treatment. - Patients with signs and symptoms of severe diseases: defined as suffering from a concomitant severe infection such as TB or any other serious known underlying disease (cardiac, renal, hepatic), - Severe malnutrition defined by BMI for age WHO reference curves for gender, Z score < -3 for subjects 6 to < 19 years; BMI < 16 for subjects > 19 years old - Patients with haemoglobin < 5g/dL - Patients with known skin disease - Patients with abnormal liver function (ALT and AST) tests of more than three times the normal range. - Patients with total bilirubin levels >1.5 times the upper normal range - Patients with serum creatinine above the upper limit of normal range - Patients with serum potassium < 3.5 mmol/L - Patients with pre-existing clinical hearing loss based on audiometry at baseline - Patients with a positive HIV test as applicable - Patients / guardian not willing to participate - Patients with history of allergy or hypersensitivity to the relevant study drug - Patients on immunomodulators therapy |
| Country | Name | City | State |
|---|---|---|---|
| Sudan | Prof. Elhassan Centre for tropical Medicine | Doka | Gedaref |
| Lead Sponsor | Collaborator |
|---|---|
| Drugs for Neglected Diseases |
Sudan,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | |
| Primary | 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 | |
| Secondary | 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 | |
| Secondary | 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. | |
| Secondary | 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. | |
| Secondary | 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 | |
| Secondary | 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. |