patients

LEISHMANIASIS
R&D MODEL & PORTFOLIO
DEVELOPMENT
New treatments for HIV/VL
co-infection for Africa
PROJECT START: September 2011
OVERALL OBJECTIVE: Develop a new treatment regimen for
patients co-infected with HIV/VL
2015 OBJECTIVE: Finalize recruitment into HIV/VL coinfection
study and conduct three interim analyses
59 patients
recruited at
2 sites
This study, initiated in 2014, aimed to
evaluate the efficacy of a combination
regimen of AmBisome ® with miltefosine,
and of AmBisome ® (at a higher dose)
monotherapy in Ethiopian patients co-infected with VL and
HIV. The AmBisome ® monotherapy arm was dropped due to
lower than expected efficacy at the time of the first interim
analysis in April 2015, and recruitment into the remaining
combination arm was also interrupted after the 2nd interim
analysis in July for the same reason. Efficacy and safety
data for the treatment period is currently under analysis.
All 59 patients recruited continue the 12 months follow-up
with pentamidine prophylaxis. The final clinical trial report
is expected in 2016.
In anthroponotic transmission areas (where disease is
transmitted by the vector from human to animals), the WHO
recommends secondary prophylaxis with drugs not given in
treating primary VL cases to avoid resistance development.
As part of the Africoleish consortium, the results from a
separate study to assess pentamidine as prophylaxis to
prevent VL relapses in HIV-VL population demonstrated
monthly pentamidine infusions led to lower rates of VL
relapses in HIV co-infected patients following one year of
treatment.
MAIN PARTNERS: Gondar University Hospital, Ethiopia; Addis Ababa
University, Ethiopia; London School of Hygiene and Tropical Medicine
(LSHTM), UK; Institute of Tropical Medicine (ITM) – Antwerp,
Belgium; Médecins Sans Frontières (MSF), The Netherlands;
Uppsala University, Sweden; Gilead Sciences, USA; LEAP; The
Netherlands Cancer Institute, The Netherlands; Utrecht University,
The Netherlands; BaseCon, Denmark; UBC, Switzerland
New treatments for PKDL
for Asia/Africa
PROJECT START: March 2015
OVERALL OBJECTIVE: Evaluate the role of PKDL in transmission
and epidemiology of Leishmania parasites and to develop
a new treatment
2015 OBJECTIVE: Carry out preparations for epidemiological,
infectivity, and PK and treatment studies
DNDi is prioritizing the management of PKDL patients who
are believed to constitute a reservoir of infection for visceral
leishmaniasis in the Indian Sub-continent and East Africa.
A synopsis has been developed for a Phase II clinical trial
of AmBisome ® alone or in combination with miltefosine,
to assess the safety and efficacy for the treatment of
PKDL patients in India and Bangladesh, and AmBisome ®
or paromomycin in combination with miltefosine for the
treatment of PKDL in Sudan.
An infectivity study will also be conducted in both countries,
to explore the role of PKDL as a potential reservoir of
L. donovani parasites which can be spread by the sandfly. This
is of particular concern in the period between epidemics, and
the trial aims to ascertain if there is a need for chemotherapy
for all PKDL patients to reduce transmission. It also aims to
identify immunological biomarkers of infectivity in VL and
PKDL cases. In preparation of the study, an insectarium was
constructed at the SK hospital in Mymensingh, Bangladesh
in 2015.
MAIN PARTNERS: International Centre for Diarrhoeal Disease
Research (ICDDR,B), Bangladesh; Rajendra Memorial Research
Institute of Medical Sciences (RMRIMS), India; Kala Azar Medical
Research Centre, India; Institute of Medical Sciences, Banaras
Hindu University, Varanasi, India; Safdarjung Hospital, Delhi, India;
Uppsala University, Sweden; Institute of Endemic Disease (IEND),
Khartoum University, Sudan; Ministry of Health, Sudan; LEAP
DNDi Annual Report 2015 › 33