EDCTP portfolio: Neglected infectious diseases

The MoxiMultiDoseMod study is evaluating the suitability of a new river blindness drug for use in mass drug administration campaigns and disease elimination.

Accelerating elimination of river blindness

The tissue-dwelling parasitic worm Onchocerca volvulus produces millions of tiny larvae (microfilariae), which live in the skin but can also invade the eye. Inflammatory reactions cause skin conditions and, in the eye, loss of sight – ‘river blindness’. Around 200 million people are at risk of infection, nearly all of them in 31 African countries.

Use of ivermectin in mass drug administration campaigns has had a major impact on disease burden. However, better treatments are required to support full elimination.

The challenge

In 2018, the US Food and Drug Administration (FDA) approved moxidectin – the first new treatment for river blindness in 20 years. In trials in Africa, moxidectin was much better than ivermectin at clearing microfilariae from the skin and had longer-lasting effects, owing to its significantly longer half-life in the body.

FDA approval of moxidectin was for single-dose use in people 12 years old and older. However, for use in mass drug administration campaigns, moxidectin would have to be used repeatedly and in children under the age of 12 years. The MoxiMultidoseMod study is comparing the safety and efficacy of moxidectin and ivermectin given annually or every six months over three years. Additionally, the study is gathering more safety data on the use of a single dose of moxidectin.

It will also undertake safety and pharmacokinetic studies to assess moxidectin usage in 4–11-year-olds. And it will carry out modelling analyses to compare the time to disease elimination and cost-effectiveness of campaigns based on use of either moxidectin or ivermectin.

The project

Moxidectin could accelerate Onchocerca elimination in countries that have lagged behind in parasite control and in fragile settings where regular mass drug administration campaigns are difficult to organise. The project will provide policymakers with key evidence on the comparative advantage of moxidectin, which could be introduced using existing mass drug administration infrastructures.

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

The tissue-dwelling parasitic worm Onchocerca volvulus produces millions of tiny larvae (microfilariae), which live in the skin but can also invade the eye. Inflammatory reactions cause skin conditions and, in the eye, loss of sight – ‘river blindness’. Around 200 million people are at risk of infection, nearly all of them in 31 African countries.

Use of ivermectin in mass drug administration campaigns has had a major impact on disease burden. However, better treatments are required to support full elimination.

In 2018, the US Food and Drug Administration (FDA) approved moxidectin – the first new treatment for river blindness in 20 years. In trials in Africa, moxidectin was much better than ivermectin at clearing microfilariae from the skin and had longer-lasting effects, owing to its significantly longer half-life in the body.

FDA approval of moxidectin was for single-dose use in people 12 years old and older. However, for use in mass drug administration campaigns, moxidectin would have to be used repeatedly and in children under the age of 12 years. The MoxiMultidoseMod study is comparing the safety and efficacy of moxidectin and ivermectin given annually or every six months over three years. Additionally, the study is gathering more safety data on the use of a single dose of moxidectin.

It will also undertake safety and pharmacokinetic studies to assess moxidectin usage in 4–11-year-olds. And it will carry out modelling analyses to compare the time to disease elimination and cost-effectiveness of campaigns based on use of either moxidectin or ivermectin.

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.

Moxidectin could accelerate Onchocerca elimination in countries that have lagged behind in parasite control and in fragile settings where regular mass drug administration campaigns are difficult to organise. The project will provide policymakers with key evidence on the comparative advantage of moxidectin, which could be introduced using existing mass drug administration infrastructures.

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.

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