Visceral leishmaniasis (VL) is fatal if left untreated; East Africa is one of the key endemic areas in the world. Untreated patients are part of the retransmission cycle and VL-HIV co-infection is an additional emerging problem.
Existing VL monotherapies are difficult to administer, toxic, costly and long with emerging resistance. Sodium stibogluconate and paromomycin (SSG&PM) has been developed as the first combination treatment for VL in East Africa and it is currently recommended as first line therapy. Although this regimen is efficacious (91% cure at 6 months post treatment), it still has limitations on toxicity and parenteral administration. A new short-course combination (shorter than the 17 days of SSG-PM) is needed to improve treatment options, ideally as an efficacious safe and field-adapted oral treatment. There is also a major need for improved and effective management of VL in HIV co-infected patients, who require a different treatment course for the VL infection and suffer from recurrent VL.
The AfriCoLeish project aims to carry out studies towards the development and delivery of a package of care for VL patients in East Africa through safe and cost-effective treatments, therefore improving current case management and contributing to disease control in the region. In the original proposal, it was planned to conduct a Phase III trial on short course combination treatment for VL with currently available drugs, pending results from LEAP 0208 clinical trial (Phase II clinical trial to evaluate two potential short course VL treatments as an alternative treatment option to the current recommended treatment of SSG&PM). In the risk assessment, it was acknowledged the risk of not observing sufficient efficacy of the regimens assessed. Indeed, the result of the trial indicated that none of the combinations tested reached the required 90% cure rate at 6 months post treatment to justify moving to a Phase III trial. Therefore, in the current proposal (June 2014), the focus will be on a replacement of the original proposal to focus on studies to assess oral treatments that can potentially be combined in a VL treatment. The studies proposed are a Phase II Proof-of-Concept trial to assess the safety and efficacy of a new oral treatment for VL (fexinidazole) and a miltefosine allometric dose pharmacokinetics and safety study in paediatric VL patients. Promising results of these two studies would allow moving forward with the development of new treatments, including the assessment of the efficacy and safety of the potential combination of fexinidazole and miltefosine for the treatment of VL, as a new oral combination treatment.
For VL-HIV co-infections the AfriCoLeish project aims to deliver an intervention to prevent relapse as well as a safe and highly effective treatment.
The project is led by a unique Consortium of European and African partners, which will design and carry out clinical studies for VL and the co-infection VL-HIV in East Africa. The studies proposed in WP1 provide a key necessary step towards not only evaluation the efficacy of a new chemical entity for VL (fexinidazole), but – subject to promising results – also opens the possibility of moving forward to a Phase III trial that could include the assessment of an innovative, affordable combination oral treatment of fexinidazole + miltefosine for VL patients in East Africa. The results of WP2 and 3 will support national programmes in the adoption of new treatments and management of VL-HIV patients. The evidence base from the trials may additionally benefit VL patients in other endemic areas, including Europe.
The original proposed timeline was to accomplish the projects by December 2015. However, due to unexpected factors, mainly the impossibility to import AmBisome in Ethiopia from June 2013 to June 2014, and revision of WP1, in the present amendment we are requesting a no cost extension until December 2016.
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FinanzierungsplanCP-FP - Small or medium-scale focused research project
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