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Short Course Regimens for Treatment of PKDL (Sudan)

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ClinicalTrials.gov Identifier: NCT03399955
Recruitment Status : Recruiting
First Posted : January 17, 2018
Last Update Posted : July 19, 2018
Sponsor:
Information provided by (Responsible Party):
Drugs for Neglected Diseases

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.

Condition or disease Intervention/treatment Phase
PKDL - Post-Kala-Azar Dermal Leishmanioid Drug: Paromomycin Drug: Ambisome Drug: Miltefosine Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 9, 2018
Estimated Primary Completion Date : May 9, 2021
Estimated Study Completion Date : May 1, 2022


Arm Intervention/treatment
Experimental: Arm 1: Paromomycin + Miltefosine
Paromomycin 20 mg/kg/d IM for 14 days combined with Miltefosine allometric BID PO dosing for 42 days
Drug: Paromomycin
Paromomycin (20 mg/kg/d) IM for 14 days

Drug: Miltefosine
Miltefosine oral (allometric dosing) for 42 days (arm 1) or 28 days (arm 2)
Other Name: Impavido

Experimental: Arm 2: Ambisome + Miltefosine
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
Drug: Ambisome
AmBisome® (20 mg/kg total dose) IV over 7 days
Other Name: Liposomal Amphotericin B

Drug: Miltefosine
Miltefosine oral (allometric dosing) for 42 days (arm 1) or 28 days (arm 2)
Other Name: Impavido




Primary Outcome Measures :
  1. Definitive Cure [ Time Frame: 12 months follow-up assessment ]
    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.

  2. Incidence of treatment-emergent adverse events [ Time Frame: from start of treatment to 12 month follow-up ]
    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 :
  1. Pharmacokinetics of Miltefosine [ 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 ]
    To assess the maximal accumulation (Cmax) of Miltefosine in the skin at the end of treatment and correlate it with achieved plasma concentrations.

  2. Pharmacokinetics of Amphotericin B (MF + Ambisome arm only) [ 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. ]
    To assess the maximal accumulation (Cmax) of Amphotericin B in the skin at the end of treatment and correlate it with achieved plasma concentrations.

  3. Pharmacokinetics of Paromomycin (MF + Paromomycin arm only) [ 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. ]
    To assess the maximal accumulation (Cmax) of Paromomycin in the skin at the end of treatment and correlate it with achieved plasma concentrations.

  4. Immune Response [ Time Frame: At screening, at day 42 (end of treatment) and at 6 month follow-up ]
    To assess the change in immune response during and after end of treatment by measuring cytokines profiles level in the peripheral blood.

  5. Parasite quantification in blood and skin [ Time Frame: At screening, day 42 (end of treatment), 3 month follow-up, 6 month follow-up and 12 month follow-up. ]
    Parasites will be quantified in blood and skin, by microscopy and qPCR, to assess the clearance before and after treatment.



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Ages Eligible for Study:   6 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03399955


Contacts
Contact: Gina M Ouattara, manager +254 20 3995000 gmouattara@dndi.org
Contact: Severine Monnerat, coordinator +41 22 907 7891 smonnerat@dndi.org

Locations
Sudan
Prof. Elhassan Centre for tropical Medicine Recruiting
Doka, Gedaref, Sudan
Contact: Brima Musa, MD         
Sponsors and Collaborators
Drugs for Neglected Diseases

Responsible Party: Drugs for Neglected Diseases
ClinicalTrials.gov Identifier: NCT03399955     History of Changes
Other Study ID Numbers: DNDi-MILT COMB-02-PKDL
First Posted: January 17, 2018    Key Record Dates
Last Update Posted: July 19, 2018
Last Verified: July 2018

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

Additional relevant MeSH terms:
Leishmaniasis, Visceral
Leishmaniasis
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Skin Diseases, Parasitic
Skin Diseases, Infectious
Skin Diseases
Amphotericin B
Paromomycin
Miltefosine
Liposomal amphotericin B
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Anti-Bacterial Agents
Antifungal Agents
Antineoplastic Agents