Description du projet
Approche d’une trithérapie pour le traitement sans complication du paludisme chez l’enfant
Le paludisme demeure un problème de santé de taille en Afrique, qui exige des solutions plus efficaces et rapidement déployables pour prévenir la résistance aux thérapies combinées à base d’artémisinine (ACT). L’artéméther-luméfantrine (AL) est abondamment utilisé en Afrique, mais préserver son efficacité est crucial pour prolonger sa durée de vie utile. L’atovaquone-proguanil (AP) constitue une alternative très productive, sûre et prometteuse. Il cible plusieurs stades parasitaires et minimise le risque de résistance croisée avec les ACT actuelles. Le projet ASAAP-plus, financé par l’UE, est un essai clinique de phase III destiné à évaluer l’efficacité d’une trithérapie dans le cadre du traitement du paludisme non compliqué à P. falciparum chez les enfants africains. Cette approche implique la combinaison de l’artéméther-luméfantrine (AL) et de l’atovaquone-proguanil (AP) et sera menée au Bénin, au Gabon, au Ghana et au Mali. Le principal critère d’évaluation sera le taux de guérison au 42e jour.
Objectif
Susceptibility to Artemisinin-based combination therapies (ACTs) currently remains high among the African Plasmodium falciparum population, but resistant mutant has been detected recently. To mitigate the risk of resistance leading to a dramatic increase in malaria related mortality, more efficient ACTs need to be urgently explored for quick deployment in Africa.
Artemether-lumefantrine (AL) is widely used and shows high efficacy and favourable safety in Africa but needs to be protected to increase its useful lifespan. Atovaquone-proguanil (AP) is highly efficacious, safe and resistant parasites are not circulating in any endemic area. AP targets multiple parasite stages -liver and blood in human host, and mosquito- through an independent mode of action, limiting the risk of cross-resistance with current ACTs.
The aim of the project is to assess the efficacy of a triple-therapy associating artemether-lumefantrine (AL) and atovaquone-proguanil (AP) for the treatment of uncomplicated P. falciparum malaria in African children in a non-inferiority comparator-controlled trial.
A phase III clinical trial will be conducted to compare safety and cure rate of a 3-day treatment course with AL+AP versus AL in 1,664 consenting 6 to 70 months children with uncomplicated malaria from Benin, Gabon, Ghana and Mali. The main outcome will be cure rate at day-42, excluding reinfections. Antimalarial pharmacokinetic parameters and post-treatment prophylactic efficacy will be estimated for the two treatments and compared. Sub-studies will look at transmission-blocking efficacy through membrane-feeding assays and gametocyte dynamics, drug resistance selection.
By proofing that AL+AP has safety and cure rate similar to AL, this project will lead to important public health-level benefits by provision of a first candidate regimen to be deployed when ACT resistance spreads throughout Africa and by decreasing human to mosquito transmission.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.2.1 - Health Main Programme
Régime de financement
HORIZON-JU-RIA - HORIZON JU Research and Innovation ActionsCoordinateur
20359 Hamburg
Allemagne