New treatments for PKDL (South Asia)
New treatments for PKDL (South Asia)
Determine the safety and efficacy of two treatment regimens for patients with PKDL in South Asia, and understand the role of PKDL in visceral leishmaniasis transmission
current phase of drug development
updated 13 Dec 2024
Post-kala-azar dermal leishmaniasis (PKDL) is a non-lethal complication of visceral leishmaniasis that can develop months or years after a person completes visceral leishmaniasis treatment. The characteristic skin rash often appears on the face and spreads to other parts of the body. PKDL does not self-heal in South Asia, and in some cases, symptoms can be severely disfiguring and stigmatizing. Better options are needed to improve upon existing treatment, which is expensive and lengthy, with poor tolerability, potential eye complications, and the requirement of contraception due to potential teratogenicity.
DNDi is prioritizing early treatment of PKDL in South Asia given the role of PKDL as a reservoir for visceral leishmaniasis infection, as demonstrated in studies in Bangladesh and India. Early treatment of PKDL patients is a critical component of visceral leishmaniasis public health and elimination strategies.
DNDi’s Phase II study in India and Bangladesh has demonstrated the suitability of two treatments – liposomal amphotericin B monotherapy and a combination of liposomal amphotericin B and short-course miltefosine – as safe, effective, shorter alternatives to long-course miltefosine for patients with PKDL in South Asia. The new treatment would shorten the treatment duration from 12 weeks to three.
Find out more about our project developing new treatments for PKDL in Eastern Africa.
Project updates
2023
The Phase II clinical trial in South Asia was completed, demonstrating the suitability of safer, shorter, efficacious treatments for PKDL as alternatives to current long-course treatments that present toxicity risks. The manuscript prepared following the Phase II trial is under review. It is expected that these alternative therapies will be recommended for patients with PKDL.
2021
The Phase II study in India and Bangladesh aims to assess the safety and efficacy of liposomal amphotericin B monotherapy and a combination of liposomal amphotericin B and miltefosine for patients with PKDL. The two-year follow-up of study participants was completed in April 2021, and final study results are expected in the first quarter of 2022.
2020
Patient follow-up for DNDi’s Phase II study in India to assess the safety and efficacy of liposomal amphotericin B (LAmB) monotherapy and a combination of liposomal amphotericin B and miltefosine (LAmB+MF) continued through 2020. Results are expected by mid-2021 following completion of a 24-month follow-up period.
2019
Patient enrolment at three sites in India (KAMRC and RMRI) and Bangladesh (icddr,b) was completed in January 2019 for DNDi’s Phase II study to assess the safety and efficacy of liposomal amphotericin B (LAmB) monotherapy and a combination of liposomal amphotericin B and miltefosine (LAmB+MF). Results are expected by mid-2021 following completion of a 24-month follow-up period.
2018
Recruitment was completed at three sites in South Asia: KAMRC and RMRI in India, and icddr,b in Bangladesh, with 126 patients enrolled in DNDi’s Phase II study to assess the safety and efficacy of liposomal amphotericin B (LAmB) monotherapy and a combination of liposomal amphotericin B and miltefosine (LAmB+MF).
The results of an infectivity study conducted in Bangladesh in 65 patients confirmed that PKDL acts as a reservoir for ongoing leishmaniasis infection. To assess long-term infectivity and the impact of treatment, the study protocol was amended to repeat xenodiagnosis on PKDL patients after treatment completion.
2017
In late 2017, recruitment started for a Phase II study in Asia to test both liposomal amphotericin B (LAmB) monotherapy and a combination of liposomal amphotericin B and miltefosine (LAmB+MF), with six patients enrolled in clinical sites in India (RMRI in Patna and KAMRC in Muzzafarpur), while a clinical site in Bangladesh is preparing for initiation. The target recruitment of 110 patients is expected to be completed by January 2019.
A PKDL infectivity study – studying the ability of a pathogen to establish a horizontal infection, that is not from parent to child – in Bangladesh completed the recruitment of 65 patients and results are under analysis.
2016
A Phase II study testing both liposomal amphotericin B (LAmB) monotherapy and a combination of liposomal amphotericin B and miltefosine (LAmB+MF) is underway in India and Bangladesh to assess the safety and efficacy for patients with PKDL. Site visits have been undertaken at the participating sites, and protocols and study documents are under finalization for submission to ethical and regulatory review. In addition, a PKDL infectivity study is under preparation in Bangladesh. Their objective is to establish the infectivity of PKDL patients to sandflies, to determine if PKDL patients maintain interepidemic transmission of visceral leishmaniasis.
News & resources
- 2 June 2024 - A phase II, non-comparative randomised trial of two treatments involving liposomal amphotericin B and miltefosine for post-kala-azar dermal leishmaniasis in India and Bangladesh, PLOS Neglected Tropical Diseases
- 10 May 2024 - Skin pharmacokinetics of miltefosine in the treatment of post-kala-azar dermal leishmaniasis in South Asia, Journal of Antimicrobial Chemotherapy
- 16 April 2024 - Post-kala-azar dermal leishmaniasis (PKDL) drug efficacy study landscape: A systematic scoping review of clinical trials and observational studies to assess the feasibility of establishing an individual participant-level data (IPD) platform, PLOS Neglected Tropical Diseases
- 28 March 2024 - 2023 R&D portfolio in review: Leishmaniasis
- 29 September 2021 - Development and validation of an HPLC-MS/MS method for the quantification of the anti-leishmanial drug miltefosine in human skin tissue, Journal of Pharmaceutical and Biomedical Analysis
- 22 July 2019 - Patients treated for visceral leishmaniasis can still transmit the disease even after completing treatment, study shows
- 22 July 2019 - The disease that strikes back
- 16 July 2019 - Quantifying the infectiousness of post-kala-azar dermal leishmaniasis towards sandflies, Clinical Infectious Diseases
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