Repurposing Ivermectin for PKDL Treatment

Assessing Safety and Efficacy of Repurposed Oral Ivermectin in PKDL Treatment

Burden: Post-Kala-Azar Dermal Leishmaniasis (PKDL) commonly follows visceral leishmaniasis (VL) caused by Leishmania donovani. It is characterized by skin lesions in which parasites can be identified, in a patient who is otherwise fully recovered from VL or exposed to L. donovani (LD) infection. It occurs in the Indian subcontinent (mainly India and Bangladesh) as well as in Africa (mainly Sudan). It is now established that PKDL patients play an important role in transmission of LD parasite where chronic PKDL patients have been implicated in major VL outbreaks in the past. Though VL cases are in decline due to extensive programmes conducted by NKEP, PKDL cases are in the rise and VL:PKDL ratio has risen from 1:0.47 to 1:1.21 from 2016 to 2020. In this current situation, elimination of PKDL cases is of crucial importance in the current VL elimination efforts in Bangladesh as well as in the Indian subcontinent.

Knowledge gap: Currently there are no satisfactory treatments for any forms of PKDL. Both miltefosine and Ambisome® as monotherapy have shown to be effective. However, with the current recommended scheme there are some drawbacks such as the length of the treatment with miltefosine alone (8-12 weeks), toxicity related to it; a high dose Ambisome® (total dose of 20 mg/kg) given frequently in 4 divided dosage often causes adverse events (e.g. pancytopania, hypokalemia, increased creatinine level etc.). There is also the potential risk for development of resistance with miltefosine as monotherapy. Ivermectin has been proven to have a significant leishmanicidal effect by several experimental studies at higher doses without significant toxicity and may offer shorter duration of treatment thus preventing prolonged hospitalization. Another possible advantage is reduction of cost. These principles can be applied to PKDL, where the need for an ambulatory treatment with a highly safe, efficacious and user friendly regimen is even more pressing as the patients feel otherwise healthy, except for the rashes.

Relevance: This study aims primarily to improve current treatment options. In addition, this will be the first human study ever in PKDL in relation to Ivermectin, in which outcome will be described in clinical, parasitological and immunological terms. Ultimately this study findings will help National Kala-Azar Elimination Program (NKAEP) to adopt specific strategies for elimination of PKDL cases.

Hypothesis (if any): Oral ivermectin in multiple doses is safe and more effective than Miltefosine for the treatment of PKDL cases.

Objectives: To measure the safety and efficacy of Ivermectin monotherapy regimen (60 mg oral on five consecutive days, for three consecutive months) in comparison to oral Miltefosine allometric dose for twelve weeks, for treating PKDL patients in Bangladesh.

Methods: This will be a comparative, open label, non-blinded, individually randomized, proof-of-concept Clinical Trial to assess the safety and efficacy of oral Ivermectin monotherapy (5 x 12 mg daily at a total dose of 60 mg per month for three consecutive months, 180 mg in total) and Miltefosine monotherapy (50 mg twice daily for 12 weeks) in treating PKDL patients in Bangladesh. All participants will be recruited at SKKRC, Mymensingh with due consent. All patients will be followed up for 12 months. Cure assessment will be performed.

Outcome measures/variables: Safety and efficacy of Ivermectin for PKDL treatment will be determined.

Study Overview

• Status: Completed
• Conditions: Post-kala-azar Dermal Leishmaniasis
• Intervention / Treatment: Drug: Ivermectin 6 Mg Oral Tablet; Drug: Miltefosine Oral Capsule

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka Division
    • Dhaka, Dhaka Division, Bangladesh, 1212
      • International Centre for Diarrhoeal Disease Research, Bangladesh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed PKDL cases of either sex
• Clinically healthy except for skin lesions
• Voluntary participation through informed, voluntary written consent

Exclusion Criteria:

• Incompliance with any inclusion criteria
• Pregnant/lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tablet Ivermectin; A cumulative dose of 60 mg Oral Ivermectin monotherapy (12 mg/day) on five consecutive days (day 1 - day 5) for three consecutive months (180 mg in total)	Drug: Ivermectin 6 Mg Oral Tablet; A cumulative dose of 60 mg Oral Ivermectin monotherapy (12 mg/day) on five consecutive days (day 1 - day 5) for three consecutive months (180 mg in total); Other Names: Tab. Ivera
Active Comparator: Capsule Miltefosine; Oral Miltefosine monotherapy for 12 weeks. 50 mg in the morning and 50 mg in the evening with meal x 84 days (Total 100 mg/day)	Drug: Miltefosine Oral Capsule; Oral Miltefosine monotherapy for 12 weeks. 50 mg in the morning and 50 mg in the evening with meal x 84 days (Total 100 mg/day); Other Names: Cap. Miltefosine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parasitological clearance	PCR in Skin samples will be negative for LD-bodies in all the Ivermectin-treated patients	Within 12 months after treatment completion
Lesion Reduction	90 % change of PKDL lesions in patients treated with Ivermectin	Within 12 months after treatment completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
No Severe Adverse Events	No Severe Adverse Events recorded in any of the patients treated with Ivermectin	Within 3 months following enrollment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects of Ivermectin	Determine the side effects of Ivermectin when administered in multiple doses	Within 3 months following enrollment

Collaborators and Investigators

• Sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh
• Investigators: Principal Investigator: Dinesh Mondal, MBBS,MD,PhD, International Centre for Diarrhoeal Disease Research, Bangladesh; Study Director: Shomik Maruf, MBBS,MPH,MSc, International Centre for Diarrhoeal Disease Research, Bangladesh

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2023
• Primary Completion (Actual): January 31, 2024
• Study Completion (Actual): January 1, 2025

Study Registration Dates

• First Submitted: February 1, 2024
• First Submitted That Met QC Criteria: February 1, 2024
• First Posted (Actual): February 9, 2024

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Euglenozoa Infections; Leishmaniasis; Leishmaniasis, Visceral; Organic Chemicals; Macrolides; Lactones; Polyketides; Ivermectin; miltefosine
• Other Study ID Numbers: PR-23023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No