Design and analysis of clinical trials for the treatment of Visceral Leishmaniasis (VL)

A series of Phase 2 and Phase 3 treatment trials for VL in East Africa conducted to identify safe, efficacious short-course treatments for VL patients in East Africa, and to increase knowledge and understanding of treatment strategies for VL in East Africa. Key results include (1) a short-course combination treatment regimen of Sodium Stibogluconate (SSG) plus PM has comparable efficacy and safety as the one-month mono-therapy regimen of SSG; (2) a single-dose short course treatment for VL using AmBisome® had inadequate efficacy to treat VL in African patients despite showing high efficacy in India with a good safety profile; (3) the short course combination treatment regimens (SSG+ AmBisome®, miltefosine +AmBisome®) and the miltefosine monotherapy treatment had lower efficacy than the target of 90% cure for taking forward into a Phase 3 trial. Pharmacokinetic data suggest possible underdosing of Miltefosine in younger, lower weight patients.