Short Course Regimens for Treatment of PKDL (Sudan)

Drugs for Neglected Diseases

Status and phase: Unknown; Phase 2

Conditions: PKDL - Post-Kala-Azar Dermal Leishmanioid

Treatments: Drug: Paromomycin; Drug: Ambisome; Drug: Miltefosine

Study type: Interventional

Funder types: Other

Identifiers

NCT03399955

DNDi-MILT COMB-02-PKDL

Details and patient eligibility

About

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.

Enrollment: 110 estimated patients

Sex: All

Ages: 6 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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110 participants in 2 patient groups

Arm 1: Paromomycin + Miltefosine

Experimental group

Description:

Paromomycin 20 mg/kg/d IM for 14 days combined with Miltefosine allometric BID PO dosing for 42 days

Treatment:

Drug: Miltefosine

Drug: Paromomycin

Arm 2: Ambisome + Miltefosine

Experimental group

Description:

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

Treatment:

Drug: Miltefosine

Drug: Ambisome