The World Health Organization (WHO) review of study results and proposed treatment guideline changes is ongoing. Countries have indicated that they will await WHO approval before implementing modifications to national treatment guidelines. The process of updating guidelines has begun in Uganda and Kenya alongside the WHO review process in order to shorten the timeline between the release of WHO recommendations and their adoption by ministries of health. DNDi joined the Leishmaniasis Technical Advisory Group Sub-Committee that was newly formed in Kenya and convened in September and November to work on the draft guidelines. The Kenyan guidelines review process remains pending, awaiting WHO recommendations.

The WHO Guideline Development Group began a review of the evidence generated in DNDi’s Phase III trial, which we hope will inform revised treatment guidelines for visceral leishmaniasis in eastern Africa. DNDi disseminated trial results to leishmaniasis technical and advisory groups in the region, as well as to communities where the studies were conducted.

Study results published in the journal Clinical Infectious Diseases in September 2022 showed that treatment with MF+PM was as effective as the current standard treatment, sodium stibogluconate (SSG) and paromomycin, but with fewer injections, a shorter treatment duration, and no risk of SSG-related cardiotoxicity. The MF+PM combination treatment also reduced the risk of subsequent post-kala-azar dermal leishmaniasis (PKDL) – a critical factor in reducing community transmission of visceral leishmaniasis. Based on the evidence gathered during the Phase III trial, miltefosine and paromomycin may be a promising alternative treatment regimen for patients with visceral leishmaniasis in Africa.

Data collected from 439 participants in the Phase III trial was monitored and cleaned through the first half of 2021, followed by data analysis in the third quarter of the year. The clinical study report was finalized in January 2022. In parallel, close-out visits were conducted across sites in Ethiopia, Kenya, Sudan, and Uganda. The results of the study appear promising and will be published in 2022.  

Enrolment in DNDi’s Phase III study was completed in May 2020, after a total of 439 patients, including both children and adults, were enrolled across seven sites in Ethiopia, Kenya, Sudan, and Uganda. The last patient follow-up visit was completed in December 2020. Monitoring visits and data analysis will continue through 2021, with study completion planned for late 2021.

By January 2020, a total of 350 patients, both children and adults, were enrolled in the study across seven sites in Ethiopia (Gondar and Abdurafi), Kenya (Kacheliba), Sudan (Dooka, Um el Kher, and Tabarak Allah), and Uganda (Amudat). Completion of patient enrollment is targeted for August 2020.

The first patient in Sudan was enrolled in January 2018.

In 2018, 126 patients were recruited in five sites in Sudan (Doka), Kenya (Kacheliba), Ethiopia (Gondar and Abdurafi) and Uganda (Amudat). Two additional sites in Sudan were scheduled for initiation in early 2019.

In 2017, the study protocol went through a joint review facilitated by WHO-AVAREF (African Vaccine Regulatory Forum), with representatives from AVAREF, the National Ethic Committees, and regulatory authorities from Ethiopia, Kenya, Sudan, and Uganda. A clinical site was initiated in Dooka, Sudan in December 2017 and the first patient recruited in January 2018. Clinical sites in Kenya (Kacheliba) and Ethiopia (Gondar) are about to be initiated, followed by additional sites in Uganda and Kenya.

The trial protocol is under finalization and will be submitted to ethics committees and regulatory authorities in early 2017.