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Short Course Regimens for Treatment of PKDL (Sudan)

Primary Purpose

PKDL - Post-Kala-Azar Dermal Leishmanioid

Status
Unknown status
Phase
Phase 2
Locations
Sudan
Study Type
Interventional
Intervention
Paromomycin
Ambisome
Miltefosine
Sponsored by
Drugs for Neglected Diseases
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for PKDL - Post-Kala-Azar Dermal Leishmanioid

Eligibility Criteria

6 Years - 60 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

  • Prof. Elhassan Centre for tropical MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm 1: Paromomycin + Miltefosine

Arm 2: Ambisome + Miltefosine

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.
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

Secondary Outcome Measures

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.
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.
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.
Immune Response
To assess the change in immune response during and after end of treatment by measuring cytokines profiles level in the peripheral blood.
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.

Full Information

First Posted
December 7, 2017
Last Updated
January 15, 2020
Sponsor
Drugs for Neglected Diseases
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1. Study Identification

Unique Protocol Identification Number
NCT03399955
Brief Title
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

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
May 9, 2018 (Actual)
Primary Completion Date
May 9, 2021 (Anticipated)
Study Completion Date
May 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Drugs for Neglected Diseases

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PKDL - Post-Kala-Azar Dermal Leishmanioid

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
110 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: Paromomycin + Miltefosine
Arm Type
Experimental
Arm Description
Paromomycin 20 mg/kg/d IM for 14 days combined with Miltefosine allometric BID PO dosing for 42 days
Arm Title
Arm 2: Ambisome + Miltefosine
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
Paromomycin
Intervention Description
Paromomycin (20 mg/kg/d) IM for 14 days
Intervention Type
Drug
Intervention Name(s)
Ambisome
Other Intervention Name(s)
Liposomal Amphotericin B
Intervention Description
AmBisome® (20 mg/kg total dose) IV over 7 days
Intervention Type
Drug
Intervention Name(s)
Miltefosine
Other Intervention Name(s)
Impavido
Intervention Description
Miltefosine oral (allometric dosing) for 42 days (arm 1) or 28 days (arm 2)
Primary Outcome Measure Information:
Title
Definitive Cure
Description
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
Title
Incidence of treatment-emergent adverse events
Description
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
Secondary Outcome Measure Information:
Title
Pharmacokinetics of Miltefosine
Description
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
Title
Pharmacokinetics of Amphotericin B (MF + Ambisome arm only)
Description
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.
Title
Pharmacokinetics of Paromomycin (MF + Paromomycin arm only)
Description
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.
Title
Immune Response
Description
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
Title
Parasite quantification in blood and skin
Description
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.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gina M Ouattara, manager
Phone
+254 20 3995000
Email
gmouattara@dndi.org
First Name & Middle Initial & Last Name or Official Title & Degree
Severine Monnerat, coordinator
Phone
+41 22 907 7891
Email
smonnerat@dndi.org
Facility Information:
Facility Name
Prof. Elhassan Centre for tropical Medicine
City
Doka
State/Province
Gedaref
Country
Sudan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brima Musa, MD

12. IPD Sharing Statement

Learn more about this trial

Short Course Regimens for Treatment of PKDL (Sudan)

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