Since 2004, DNDi and LEAP have embarked on a clinical research programme with two specific objectives: to geographically extend all currently available VL drugs and to develop one to two new treatments.

The LEAP 0208 Study, coordinated by DNDi and LEAP, to assess combinations of existing drugs to treat VL in Africa, aimed to evaluate the safety and efficacy of miltefosine monotherapy, AmBisome®-SSG, and AmBisome®-miltefosine combination treatments. Recruitment started in Kenya and Sudan in 2010 and ended in March 2012. Miltefosine, a drug originally developed for the treatment of breast cancer metastasis, is the only orally-administered drug against VL. It is registered and used in India and in some countries in Latin America.

The trial collected safety, efficacy, and pharmacokinetic data on miltefosine to geographically extend its use into East Africa. In addition, combination treatments of AmBisome® with either miltefosine or SSG were evaluated. Efficacy results were below the expected 91% of the current first line treatment with SSG&PM (AmBisome®+SSG, 87% cure rate after 6 months follow up; AmBisome®+miltefosine, 77%; miltefosine, 72%). Important PK/PD findings were obtained in this study related to the under exposure of miltefosine in children.

The slower parasite clearance when given a single infusion of AmBisome® as compared with multiple doses was proven earlier (LEAP AMBI 0106). Following discussions with experts and LEAP principal investigators, and taking into account the high price of hypothetical treatment (which would not fulfill the target product profile), the decision was taken to not proceed to a Phase III trial of any combination. The project is rephrasing priorities in order to study the PK of miltefosine in children treated following allometric dosing.

The results of the LEAP AMBI 0106 trial that aimed to determine the minimum dose of AmBisome® which is efficacious, safe, and cost-effective, to treat VL in Africa, were published in January 2014.(1)

Leadership: Head of DNDi Africa: Monique Wasunna; Head of VL Clinical Programme: Jorge Alvar; Clinical Manager: Fabiana Alves; Project Coordinator: Clélia Bardonneau