patients

LEISHMANIASIS
R&D MODEL & PORTFOLIO
TRANSLATION
Fexinidazole/Miltefosine
Combination
PROJECT START: 2013
OVERALL OBJECTIVE: Develop an oral-only therapy for VL by 2022
2015 OBJECTIVES: Initiate allometric dosing study of miltefosine
in children. Prepare for a drug-drug interaction study on
fexinidazole-miltefosine
30 paediatric
patients recruited
at 4 sites
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.
MAIN PARTNERS: Institute of Endemic Disease (IEND), Khartoum
University, Sudan; Kenya Medical Research Institute (KEMRI),
Kenya; Makerere University, Uganda; Amudat Hospital, Uganda;
Leishmaniasis East Africa Platform (LEAP); Kacheliba District
Hospital, Kenya; Uppsala University, Sweden; Utrecht University,
The Netherlands; London School of Hygiene and Tropical Medicine
(LSHTM), UK; Koninklijk Instituut voor de Tropen (KIT), The
Netherlands; The Netherlands Cancer Institute, The Netherlands;
PhinC, France; Centres d’Investigation Clinique des Centres
Hospitaliers Universitaires de Clermont-Ferrand, Lille et Bichat-
Claude Bernard, France; SGS, Belgium; Cardiabase, France; Optimed,
France; UBC, Switzerland.
DNDi Annual Report 2015 › 31