Fexinidazole/Miltefosine Combination (VL)

Fexinidazole has shown potent activity against L. donovani in vitro and in vivo in a VL mouse model, and studies in healthy volunteers found it to be safe when given as a single dose or as repeated dosing after 14 days. Furthermore, fexinidazole is in late stage development for HAT with a good safety profile.

A Phase II proof-of-concept study initiated in 2013 assessed the safety and efficacy of fexinidazole for the treatment of primary VL adult patients in Sudan, and enrolled 14 patients. All patients showed clinical improvement during treatment and the majority had parasite clearance (by microscopy) at the end of treatment. Three patients remained cured until 6 months follow-up, however the response was not sustained in other patients and relapses were observed. The study was interrupted in 2014 as it failed to show conclusive efficacy in the majority of patients. Miltefosine is the only other oral drug currently available and will be evaluated in combination with fexinidazole in Eastern Africa. A previous study carried out in Africa indicated miltefosine was underdosed in children as compared to adults, and that dose adjustment was required. A study to assess safety and efficacy of miltefosine using an allometric dosing in children with VL was initiated in Kenya and Uganda in June 2015, recruitment completed in September, and patient follow up will end in 2016. As the ultimate goal is to develop a combination of fexinidazole and miltefosine, a drug-drug interaction study in normal healthy volunteers to assess the pharmacokinetics and safety of the concomitant administration of fexinidazole and miltefosine has been prepared.