Phase II clinical trials in South Asia and Sudan were completed, both demonstrating the suitably of safe and efficacious shorter treatments for PKDL as alternatives to current long-course treatments that present toxicity risks. Findings from the Phase II trial in Sudan were published in November 2023; the manuscript prepared following the Phase II trial in South Asia is under review. It is expected that these alternative therapies will be recommended for patients with PKDL.

The final clinical study report for the Phase II PKDL trial in Sudan was released in January 2022 and shared with the Sudanese regulatory agency and ethical approval committees. Discussions regarding potential changes to PKDL treatment guidelines are ongoing with the Ministry of Health. The study manuscript is expected to be published in the second quarter of 2023.

The Phase II study in Sudan testing both liposomal amphotericin B in combination with miltefosine, and paromomycin in combination with miltefosine, completed enrolment and follow-up of all 110 patients in May 2021. Final study results are expected in the first quarter of 2022. 

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. 

DNDi’s Phase II study in Sudan testing both liposomal amphotericin B in combination with miltefosine, and paromomycin in combination with miltefosine, completed enrolment of 110 patients in May 2020. Patient follow-up will continue through the first half of 2021; results are expected by the end of 2021.

Patient follow-up for DNDi’s Phase II study in India to assess the safety and efficacy of liposomal amphotericin B monotherapy and a combination of liposomal amphotericin B and miltefosine continued through 2020. Results are expected by mid-2021 following completion of a 24-month follow-up period.

A Phase II study to test both liposomal amphotericin B in combination with miltefosine, and paromomycin in combination with miltefosine began in Dooka, Sudan in 2018 and had enrolled 73 patients by January 2020. Results are expected by 2021.

In South Asia, patient enrollment in 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 monotherapy and a combination of liposomal amphotericin B and miltefosine. Results are expected by mid-2021 following completion of a 24-month follow-up period.

In Sudan, work continues at University of Gedaref to establish a sandfly colony in preparation for infectivity studies in PKDL and visceral leishmaniasis patients. A similar study completed in Bangladesh in 2018 confirmed that PKDL acts as a reservoir for ongoing leishmaniasis infection.

In Sudan, a Phase II study to test both liposomal amphotericin B in combination with miltefosine, and paromomycin in combination with miltefosine began in Dooka, Sudan in 2018 and had recruited 39 patients by January 2019. Results are expected by mid-2021.

In South Asia, with 126 patients enrolled in three sites in India (KAMRC and RMRI) and Bangladesh (icddr,b), recruitment has been completed in DNDi’s Phase II study to assess the safety and efficacy of liposomal amphotericin B monotherapy and a combination of liposomal amphotericin B and miltefosine.

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. In Sudan, preparation for a similar infectivity study is underway.

In late 2017, recruitment started for a Phase II study in Asia to test both liposomal amphotericin B monotherapy and a combination of liposomal amphotericin B and miltefosine, 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 Phase II study to test both AmBisome in combination with miltefosine, and paromomycin in combination with miltefosine is under preparation in Sudan. Target recruitment will be 110 patients over two years.

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. In Sudan, the preparation of an insectarium for infectivity studies continues.

A Phase II study testing both liposomal amphotericin B monotherapy and a combination of liposomal amphotericin B and miltefosine is underway in India and Bangladesh to assess the safety and efficacy for patients with PKDL. A separate Phase II study to assess the safety and efficacy of both liposomal amphotericin B in combination with miltefosine, and paromomycin in combination with miltefosine, is planned in Sudan. Site visits have been undertaken at all participating sites in the three countries, and protocols and study documents are under finalization for submission to ethical and regulatory review. In addition, two PKDL infectivity studies are under preparation in Bangladesh and Sudan. Their objective is to establish the infectivity of PKDL patients to sand flies, to determine if PKDL patients maintain interepidemic transmission of visceral leishmaniasis.