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[e-drug] Phase III Ethiopia Clin. Study - 2 Treatments for HIV-Visceral Leishmaniasis Co-infection

E-DRUG: Phase III Ethiopia Clin. Study - 2 Treatments for HIV-Visceral 
Leishmaniasis Co-infection


On 6 October 2014, the international research & development (R&D) consortium, 
AfriCoLeish, formed by six research organizations from East Africa and Europe, 
has launched a Phase III clinical study to address the extreme difficulty in 
treating visceral leishmaniasis (VL) in patients who also are HIV-positive. 

The study will assess the efficacy and the safety of two treatments: a 
combination treatment of AmBisome® and miltefosine, and AmBisome® alone. This 
is the first randomized clinical trial in Africa to confirm the World Health 
Organization's recommendation for HIV-VL treatment. Two sites, Gondar and 
Abdurafi, in northwest Ethiopia, one of the highest burden areas in the world, 
have begun recruiting patients.

HIV infection and VL, fatal without treatment, both affect the immune system of 
the patients. When the two diseases occur together, treatment of both diseases 
becomes more challenging. The risk of death from VL is nine times higher in 
patients who are co-infected with HIV. VL also accelerates the progression of 
HIV. Relapses of VL in patients co-infected with HIV are also very common, 
affecting half of treated patients within a year of initial treatment, and 
overall VL cure rates are significantly lower. An emerging global problem, 
VL-HIV cases are reported in 35 countries worldwide, spanning Southern Europe, 
East Africa, the Indian subcontinent, and Latin America. One of the hardest hit 
areas in Africa is northwest Ethiopia, where anywhere from 20% to 40% of 
patients with VL were found to be also infected with HIV.

'Treating patients that suffer both HIV and visceral leishmaniasis is a real 
battle for clinicians. Research strongly suggests that we need to strike the 
right balance between stronger treatments and safer treatments', said Koert 
Ritmeijer, PhD, Health Advisor, Medecins Sans Frontieres.

'Combining better initial cure treatments and preventing relapses will be a 
major step forward for our patients, who today fear that the diseases, which 
can be managed when they occur separately, often become a death sentence when 
they occur together. We have to do all we can to provide the most affected, a 
highly vulnerable migrant population, with an appropriate response', said Dr 
Ermias Diro, Principal Site Investigator, University of Gondar.

The Phase III clinical study conducted in Gondar and Abdurafi, Ethiopia, will 
assess the efficacy and safety of the combination of AmBisome® (30mg/kg total 
dose) and miltefosine (50mg or 100mg/day depending on the patient's weight), 
and AmBisome® alone (40mg/kg total dose). Total treatment duration is 28 days, 
if the tests show that the patient is parasite-negative (at day 29). 
Thereafter, the patient will start a secondary prophylaxis treatment aimed at 
preventing VL relapses and a one-year follow-up phase. A total of 132 patients 
will be recruited for the trial.

'Visceral leishmaniasis, notably in East Africa, is among the most neglected of 
all neglected tropical diseases. The work of this consortium to address the 
additional challenge of co-infection with HIV in Ethiopia is vital as it has 
begun to tackle one of the most challenging endemic areas and aspects of this 
fatal disease', said Dr Jorge Alvar, Head of Leishmanisis Programme, DNDi.

This clinical trial is conducted by DNDi (sponsor) in collaboration with 
MSF-Holland (co-sponsor); the University of Gondar (UoG), Ethiopia; the 
Institute of Tropical Medicine (ITM) Antwerp, Belgium; the London School of 
Hygiene & Tropical Medicine, UK; and is funded by the European Union (EU FP7); 
the Swiss Agency for Development and Cooperation (SDC), Switzerland; Medecins 
Sans Frontieres; the Federal Ministry of Education and Research (BMBF) through 
KfW, Germany; the Medicor Foundation, Liechtenstein; and other private donors.

Facts about the study:

·         Overall objective: identify a safe and effective treatment for VL in 
HIV co-infected patients

·         Study design: a randomized, parallel arm, open-label clinical study

·         Treatment dosing schedule:

          o   AmBisome® monotherapy: 40mg/kg total dose: intravenous infusion 
5mg/kg on day 1-5, 10, 17, 24

          o   AmBisome®: 30mg/kg total dose: intravenous infusion 5mg/kg on day 
1, 3, 5, 7, 9, 11 and miltefosine: every day for 28 days, with 50mg/day (for 
patient weighting ≤ 25 kg) and 100 mg/day (for patient weighting > 25 kg)

·         Study duration:

          o   Treatment duration is 28 days or 56 days in case of extended 
treatment (if tissue aspirate is parasite positive at day 29 and the patient is 
well). When the patients are tested parasite negative, they are eligible for a 
secondary prophylaxis – pentamidine 4mg/kg intramuscular injection or 
intravenous infusion once a month – and enter a one-year follow-up phase. At 
any stage as of day 29, if the patients are unwell, they receive a rescue 

·         AmBisome® supply for the study is donated by Gilead. Pentamidine 
supply for the study is donated by Sanofi.

About visceral leishmaniasis (VL or kala-azar)

Visceral leishmaniasisis a neglected tropical disease caused by Leishmania 
donovani or L. infantum. There are an estimated 300,000 new cases of VL per 
annum. Fatal if left untreated, the disease kills approximately 40,000 people 
every year, and 90% of cases occur in Bangladesh, Brazil, Ethiopia, India, 
South Sudan, and Sudan. VL is characterized by prolonged fever and 
splenomegaly. The current therapies administered include pentavalent 
antimonials (sodium stibogluconate and meglumine antimoniate), AmBisome®, 
miltefosine, and paromomycin.

About AfriCoLeish: <http://www.africoleish.org>

A research and development (R&D) international consortium, AfriCoLeish is 
supported by the European Union Seventh Framework Programme (EU FP7) through a 
grant of €3 million. The project aims to test new treatments for visceral 
leishmaniasis (VL or kala-azar) in East Africa and co-infection of the disease 
with HIV in Ethiopia. AfriCoLeish brings together six organizations from Europe 
and East Africa with vast experience in R&D and treatment of HIV and kala-azar, 

- Drugs for Neglected Diseases initiative (DNDi): 
- Institute of Tropical Medicine (ITM) in Antwerp: www.itg.be<http://www.itg.be>
- London School of Hygiene & Tropical Medicine: 
- Medecins Sans Frontieres (MSF, The Netherlands): 
- Institute of Endemic Diseases, University of Khartoum (IEND), Sudan: 
- University of Gondar (UoG), Ethiopia:  www.uog.edu.et<http://www.uog.edu.et>

Gabrielle Landry Chappuis
Head of Communication and Advocacy
Drugs for Neglected Diseases initiative – DNDi
15 Chemin Louis-Dunant, 1202 Geneva, Switzerland
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