EDCTP portfolio: Malaria

The WANECAM II study is accelerating the development of a new class of antimalarial drug that may have significant advantages over existing treatments.

Advancing a new class of antimalarial drug

Despite much progress, malaria control has stalled in recent years, with deaths still in excess of 400,000 a year in Africa, most of them young children.

In addition, the emergence in South-East Asia of resistance to the mainstay of malaria treatment, artemisinin combination therapy (ACT), is of grave concern and emphasises the need to identify possible alternative treatments.

The challenge

With EDCTP funding, the WANECAM consortium played a key role in the evaluation of new antimalarial formulations suitable for use in children. With additional funding through the EDCTP2 programme, the WANECAM II is now a pivotal partner in a global collaboration advancing a novel antimalarial treatment that does not include artemisinin-based drugs. The collaboration includes the not-for-profit Medicines for Malaria Venture and the Novartis pharmaceutical company.

WANECAM II is focusing on a new antimalarial drug, KAF156 (ganaplacide), from an entirely novel chemical class. Its mode of action appears to be different to that of artemisinin-based drugs, and it is highly active against several stages of the malaria parasite and against Plasmodium vivax as well as P. falciparum.  It is being teamed up with a new formulation of an existing antimalarial, lumefantrine, that is less affected by food intake and would allow the new combination to be given as a single dose.

The WANECAM II team is carrying out a phase IIb trial with groups of children from 12 years down to six months of age. A phase III trial will then be conducted in adults and infants of six months of age and older.

The project

WANECAM II will provide key evidence on the safety and efficacy of KAF156–lumefantrine in Africans, including children, who are most at risk from malaria. Positive data would support submissions to regulatory authorities for approval of the new combination. KAF156–lumefantrine would be an alternative to artemisinin-based combination therapies, but would also have advantages, including the need for just a single dose and the possibility of blocking parasite transmission to mosquitoes, which would prevent the spread of the infection to others.

In addition, the project is further strengthening research capacity across the WANECAM network, including in Niger, which to date has not had a strong medical research base.

Impact


crucial in

widening African

children’s access

to antiretrovirals

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

Despite much progress, malaria control has stalled in recent years, with deaths still in excess of 400,000 a year in Africa, most of them young children.

In addition, the emergence in South-East Asia of resistance to the mainstay of malaria treatment, artemisinin combination therapy (ACT), is of grave concern and emphasises the need to identify possible alternative treatments.

With EDCTP funding, the WANECAM consortium played a key role in the evaluation of new antimalarial formulations suitable for use in children. With additional funding through the EDCTP2 programme, the WANECAM II is now a pivotal partner in a global collaboration advancing a novel antimalarial treatment that does not include artemisinin-based drugs. The collaboration includes the not-for-profit Medicines for Malaria Venture and the Novartis pharmaceutical company.

WANECAM II is focusing on a new antimalarial drug, KAF156 (ganaplacide), from an entirely novel chemical class. Its mode of action appears to be different to that of artemisinin-based drugs, and it is highly active against several stages of the malaria parasite and against Plasmodium vivax as well as P. falciparum.  It is being teamed up with a new formulation of an existing antimalarial, lumefantrine, that is less affected by food intake and would allow the new combination to be given as a single dose.

The WANECAM II team is carrying out a phase IIb trial with groups of children from 12 years down to six months of age. A phase III trial will then be conducted in adults and infants of six months of age and older.

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.

WANECAM II will provide key evidence on the safety and efficacy of KAF156–lumefantrine in Africans, including children, who are most at risk from malaria. Positive data would support submissions to regulatory authorities for approval of the new combination. KAF156–lumefantrine would be an alternative to artemisinin-based combination therapies, but would also have advantages, including the need for just a single dose and the possibility of blocking parasite transmission to mosquitoes, which would prevent the spread of the infection to others.

In addition, the project is further strengthening research capacity across the WANECAM network, including in Niger, which to date has not had a strong medical research base.

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.