Compare the efficacy and safety of two combination regimens of miltefosine and paromomycin with the current standard treatment
current phase of drug development
updated 15 Feb 2023
Based on the good efficacy of the miltefosine and paromomycin (MF+PM) combination therapy in South Asia, and on the need for an alternative and safer treatment to replace sodium stibogluconate, a Phase III study was launched in 2018 to compare a combination regimen of miltefosine and paromomycin against the current standard visceral leishmaniasis treatment, sodium stibogluconate and paromomycin. The trial was conducted by AfriKADIA Consortium partners in Kenya, Ethiopia, Sudan, and Uganda.
If this new combination is proven safe and effective, treatment would no longer rely on sodium stibogluconate, an injectable drug with potential toxic side effects, but would be replaced with miltefosine, an oral drug. A safer, more field-adapted, patient-friendly treatment would particularly benefit children, who represent a high proportion of the population at risk in East Africa.
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.
News & resources
- 18 February 2023 - Africa is winning the war against Neglected Tropical Diseases
- 27 January 2023 - Eliminating neglected diseases in Africa: there are good reasons for hope
- 26 January 2023 - Avancée « majeure » dans la lutte contre les maladies tropicales négligées, SciDev.Net
- 31 October 2022 - New treatment for kala-azar spells renewed hope for patients, People Daily
- 17 October 2022 - Kala-azar: There is now better, shorter treatment, The Standard
- 10 October 2022 - Drug combination offers shorter, more effective visceral leishmaniasis treatment, Nature Africa
- 10 October 2022 - The world versus leishmaniasis, The Medicine Maker
- 7 October 2022 - Leishmaniasis: New drug works quicker and with less pain, BBC
- 3 October 2022 - DNDi 2022 Projects of the Year recognize partners and colleagues for their work in developing new treatments for leishmaniasis
- 30 September 2022 - New, combined treatment for VL patients becomes effective in East Africa, Ethiopian Herald
- 30 September 2022 - Hope for kala-azar patients as new treatment is discovered, Nation
- 29 September 2022 - New treatment for visceral leishamaniasis effective – study says, Science Africa
- 29 September 2022 - New leishmaniasis treatment shows effectiveness in Eastern Africa, New Business Ethiopia
- 29 September 2022 - Better, shorter combination treatment for people with visceral leishmaniasis shown to be effective in Eastern Africa
- 29 September 2022 - The Science Explained: Evaluating an alternative treatment regimen for visceral leishmaniasis in Eastern Africa
- 27 September 2022 - Paromomycin and miltefosine combination as an alternative to treat patients with visceral leishmaniasis in Eastern Africa: A randomized, controlled, multicountry trial, Clinical Infectious Diseases
- 13 April 2018 - Clinical trial to find new treatment for visceral leishmaniasis begins in eastern Africa
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