Short Course Regimens for Treatment of PKDL (Sudan)

NCT03399955 | Unknown Phase 2

• 1 other identifier: DNDi-MILT COMB-02-PKDL
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

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.

Conditions

PKDL - Post-Kala-Azar Dermal Leishmanioid

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (5)

• Pharmacokinetics of Miltefosine

  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

• Pharmacokinetics of Amphotericin B (MF + Ambisome arm only)

  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.

• Pharmacokinetics of Paromomycin (MF + Paromomycin arm only)

  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.

• Immune Response

  At screening, at day 42 (end of treatment) and at 6 month follow-up

• Parasite quantification in blood and skin

  At screening, day 42 (end of treatment), 3 month follow-up, 6 month follow-up and 12 month follow-up.

Study Arms (2)

Arm 1: Paromomycin + Miltefosine

EXPERIMENTAL

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

Drug: Paromomycin; Drug: Miltefosine

Arm 2: Ambisome + Miltefosine

EXPERIMENTAL

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; Drug: Miltefosine

Interventions

Paromomycin DRUG

Paromomycin (20 mg/kg/d) IM for 14 days

Arm 1: Paromomycin + Miltefosine

Ambisome DRUG

AmBisome® (20 mg/kg total dose) IV over 7 days

Also known as: Liposomal Amphotericin B

Arm 2: Ambisome + Miltefosine

Miltefosine DRUG

Miltefosine oral (allometric dosing) for 42 days (arm 1) or 28 days (arm 2)

Also known as: Impavido

Arm 1: Paromomycin + Miltefosine; Arm 2: Ambisome + Miltefosine

Eligibility Criteria

• Age: 6 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead

Study Sites (1)

Prof. Elhassan Centre for tropical Medicine

Doka, Al Qaḑārif, Sudan

RECRUITING

Related Publications (2)

• Torres A, Younis BM, Alamin M, Tesema S, Bernardo L, Solana JC, Moreno J, Mustafa AA, Alves F, Musa AM, Carrillo E. Differences in the Cellular Immune Response during and after Treatment of Sudanese Patients with Post-kala-azar Dermal Leishmaniasis, and Possible Implications for Outcome. J Epidemiol Glob Health. 2024 Sep;14(3):1167-1179. doi: 10.1007/s44197-024-00270-0. Epub 2024 Jul 15.

  PMID: 39007942 DERIVED

• Younis BM, Mudawi Musa A, Monnerat S, Abdelrahim Saeed M, Awad Gasim Khalil E, Elbashir Ahmed A, Ahmed Ali M, Noureldin A, Muthoni Ouattara G, Nyakaya GM, Teshome S, Omollo T, Ochieng M, Egondi T, Mmbone M, Chu WY, Dorlo TPC, Zijlstra EE, Wasunna M, Alvar J, Alves F. Safety and efficacy of paromomycin/miltefosine/liposomal amphotericin B combinations for the treatment of post-kala-azar dermal leishmaniasis in Sudan: A phase II, open label, randomized, parallel arm study. PLoS Negl Trop Dis. 2023 Nov 21;17(11):e0011780. doi: 10.1371/journal.pntd.0011780. eCollection 2023 Nov.

  PMID: 37988402 DERIVED

MeSH Terms

Interventions

Paromomycin; liposomal amphotericin B; miltefosine

Intervention Hierarchy (Ancestors)

Aminoglycosides; Glycosides; Carbohydrates

Central Study Contacts

Gina M Ouattara, manager

CONTACT

+254 20 3995000; gmouattara@dndi.org

Severine Monnerat, coordinator

CONTACT

+41 22 907 7891; smonnerat@dndi.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: January 17, 2018
• Study Start: May 9, 2018
• Primary Completion: May 9, 2021
• Study Completion: May 1, 2022
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

SU (1)