Publications

Funding for clinical research |drugs, vaccines, microbicides, diagnostics | HIV/AIDS, tuberculosis, malaria, other infectious diseases |sub-Saharan Africa

EDCTP portfolio: Malaria

The SINDOFO study will generate data on a new antimalarial drug combination that could cure malaria in a single dose.

Advancing a single-dose treatment of malaria

Antimalarial drugs in the artemisinin family are highly effective at killing malaria parasites. They act rapidly and are swiftly cleared from the body. They are generally combined with a second, slower-acting drug in artemisinin-based combination therapies (ACTs), to kill any remaining parasites and to reduce the risk of resistance.

Because they are eliminated rapidly, artemisinin-based drugs need to be given in a series of doses over several days, although this can be reduced to three days in ACTs. A single-dose treatment, however, would be much more convenient.

 

The challenge

The SINDOFO project is evaluating a new drug combination that does not contain an artemisinin-based drug and can be given in a single dose. It comprises artefenomel (OZ439), which has chemical features in common with artemisinin but is active against artemisinin-resistant parasites, and ferroquine, a modified form of chloroquine, which was widely used to treat malaria before widespread resistance emerged. OZ439 is the first antimalarial to be developed simultaneously for adults and children.

The project is running a large phase III trial on a single-dose formulation of OZ439–ferroquine in four African countries, in adults and children, who are likely to make up most of the study population. The new formulation is being compared with the usual standard of care.

The project

The SINDOFO trial will provide key data on a novel, non-ACT combination treatment that preliminary data suggest will be as potent as ACTs. With growing concerns about the spread of resistance to artemisinin-based drugs globally, OZ439–ferroquine would provide an important alternative. In addition, the single-dose treatment would be a major benefit in terms of drug delivery and adherence.

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

Antimalarial drugs in the artemisinin family are highly effective at killing malaria parasites. They act rapidly and are swiftly cleared from the body. They are generally combined with a second, slower-acting drug in artemisinin-based combination therapies (ACTs), to kill any remaining parasites and to reduce the risk of resistance.

Because they are eliminated rapidly, artemisinin-based drugs need to be given in a series of doses over several days, although this can be reduced to three days in ACTs. A single-dose treatment, however, would be much more convenient.

 

The SINDOFO project is evaluating a new drug combination that does not contain an artemisinin-based drug and can be given in a single dose. It comprises artefenomel (OZ439), which has chemical features in common with artemisinin but is active against artemisinin-resistant parasites, and ferroquine, a modified form of chloroquine, which was widely used to treat malaria before widespread resistance emerged. OZ439 is the first antimalarial to be developed simultaneously for adults and children.

The project is running a large phase III trial on a single-dose formulation of OZ439–ferroquine in four African countries, in adults and children, who are likely to make up most of the study population. The new formulation is being compared with the usual standard of care.

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 SINDOFO trial will provide key data on a novel, non-ACT combination treatment that preliminary data suggest will be as potent as ACTs. With growing concerns about the spread of resistance to artemisinin-based drugs globally, OZ439–ferroquine would provide an important alternative. In addition, the single-dose treatment would be a major benefit in terms of drug delivery and adherence.

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