EDCTP portfolio: Neglected infectious diseases

The HAT-R-ACC study is assessing whether a new treatment is effective against a type of sleeping sickness mainly found in East Africa.

Treating East African sleeping sickness

Sleeping sickness (human African trypanosomiasis, HAT) is a parasitic disease that can be fatal without effective treatment. It is usually caused by a single-celled parasite, Trypanosoma brucei gambiense, but a relative, T. b. rhodesiense, can cause a similar but more acute disease (r-HAT). r-HAT is found mainly in East Africa, with Malawi and Uganda accounting for 88% of global infections.

Treatment of r-HAT has traditionally relied on either a toxic arsenic-based drug, melarsopol, or a less toxic but difficult-to-administer drug, suramin, depending on how far disease has progressed.

The challenge

Recently, a highly effective, safe oral treatment – fexinidazole – has been developed for HAT caused by T.b. gambiense. The HAT-R-ACC study will determine whether fexinidazole could also be adopted for treatment and control of r-HAT.

The HAT-R-ACC project will carry out a clinical trial to determine whether fexinidazole is a suitable alternative to replace both melarsopol and suramin at different stages of disease. The project will also work with local communities to raise awareness of the condition and treatment, and build local capacity to undertake scientific studies.

The project

The study will fill a major gap in knowledge on a rare but deadly disease having a significant regional impact, addressing an urgent WHO request for information on methods of r-HAT control in East Africa. Fexinidazole could also provide a key tool in the ultimate elimination of r-HAT in Africa.

Impact


test the safety and efficacy of this new formulation in young children

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

EDCTP portfolio: HIV & HIV-associated infections

The challenge

Sleeping sickness (human African trypanosomiasis, HAT) is a parasitic disease that can be fatal without effective treatment. It is usually caused by a single-celled parasite, Trypanosoma brucei gambiense, but a relative, T. b. rhodesiense, can cause a similar but more acute disease (r-HAT). r-HAT is found mainly in East Africa, with Malawi and Uganda accounting for 88% of global infections.

Treatment of r-HAT has traditionally relied on either a toxic arsenic-based drug, melarsopol, or a less toxic but difficult-to-administer drug, suramin, depending on how far disease has progressed.

Recently, a highly effective, safe oral treatment – fexinidazole – has been developed for HAT caused by T.b. gambiense. The HAT-R-ACC study will determine whether fexinidazole could also be adopted for treatment and control of r-HAT.

The HAT-R-ACC project will carry out a clinical trial to determine whether fexinidazole is a suitable alternative to replace both melarsopol and suramin at different stages of disease. The project will also work with local communities to raise awareness of the condition and treatment, and build local capacity to undertake scientific studies.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The study will fill a major gap in knowledge on a rare but deadly disease having a significant regional impact, addressing an urgent WHO request for information on methods of r-HAT control in East Africa. Fexinidazole could also provide a key tool in the ultimate elimination of r-HAT in Africa.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact

L’homme RF et al. Nevirapine, stavudine and lamivudine pharmacokinetics in African children on paediatric fixed-dose combination tablets. AIDS. 2008;22(5):557–65.

Mulenga V et al. Abacavir, zidovudine, or stavudine as paediatric tablets for African HIVinfected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Lancet Infect Dis. 2016;16(2):169–79.

WHO. Guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. 2010.

WHO. Consolidated guidelines on the use of antiretroviral drugs
for treating and preventing

HIV infection: Recommendations for a public health approach
(second edition). 2016

Projects: Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens (CHAPAS): CHAPAS-1 and -3

Project lead: Professor Chifumbe Chintu, University Teaching Hospital, Zambia (CHAPAS-1); Dr Veronica Mulenga, University Teaching Hospital, Zambia (CHAPAS-3)

Target population(s): Children with HIV

Sample size: 71 (CHAPAS-1); 480 (CHAPAS-3)

Countries involved: Ireland, the Netherlands, the UK, the USA, Zambia (CHAPAS-1); Uganda, Zambia (CHAPAS-3)

Project duration: 2005–2009 (CHAPAS-1); 2010 –2011 (CHAPAS-3)

EDCTP funding: €1.2M (CHAPAS-1); €4.6M (CHAPAS-3)

Total project funding: €1.2M (CHAPAS-1); €5.0M

About us

The European & Developing Countries Clinical Trials Partnership (EDCTP) is a public–public partnership between 14 European and 16 African countries, supported by the European Union. EDCTP’s vision is to reduce the individual, social and economic burden of poverty-related infectious diseases by affecting sub-Saharan Africa. EDCTP’s mission is to accelerate the development of new or improved medicinal products for the identification, treatment and prevention of infectious diseases, including emerging and re-emerging diseases, through pre- and postregistration clinical studies, with emphasis on phase II and III clinical trials. Our approach integrates conduct of research with development of African clinical research capacity and networking. The second EDCTP programme is implemented by the EDCTP Association supported under Horizon 2020, the European Union’s Framework Programme for Research and Innovation.

Contact us

For more information, please contact us or leave a message using this form.
Please enter your name
Please enter a correct e-mail address
Please enter a comment
Thank you! Your message has been sent.
Something went wrong while submitting the form. Try again.

Share this publication

Forward this page by e-mail or share it directly on social media.

Search

Enter a search term to search the EDCTP publications.
Minimal length to search is 3 characters

This publication uses cookies

We use functional and analytical cookies to improve our website. In addition, third parties place tracking cookies to display personalised advertisements on social media. By clicking accept you consent to the placement of these cookies.