Clinical trial NCT03399955: Short Course Regimens for Treatment of PKDL (Sudan)
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: PKDL - Post-Kala-Azar Dermal Leishmanioid
Lead sponsor: Drugs for Neglected Diseases
Sponsor class: OTHER
First posted: 2018-01-17
Enrollment: 110
Sex: ALL
Minimum age (years): 6
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Definitive Cure
timeFrame: 12 months follow-up assessment
measure: Incidence of treatment-emergent adverse events
timeFrame: from start of treatment to 12 month follow-up
Secondary outcomes:
measure: Pharmacokinetics of Miltefosine
timeFrame: 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
measure: Pharmacokinetics of Amphotericin B (MF + Ambisome arm only)
timeFrame: 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.
measure: Pharmacokinetics of Paromomycin (MF + Paromomycin arm only)
timeFrame: 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.
measure: Immune Response
timeFrame: At screening, at day 42 (end of treatment) and at 6 month follow-up
measure: Parasite quantification in blood and skin
timeFrame: At screening, day 42 (end of treatment), 3 month follow-up, 6 month follow-up and 12 month follow-up.
Other outcomes:
Locations:
city: Doka
country: Sudan
facility: Prof. Elhassan Centre for tropical Medicine
state: Gedaref
Study officials:
References: