Advancing child-friendly artesunate-amodiaquine taste mask coated micro pellets to combat the threat of artemisinin resistant malaria in Africa

Artemisinin resistant Plasmodium falciparum is spreading alarmingly in Sub-Saharan Africa (SSA) and has compromised the efficacy of artemether lumefantrine. To meet this threat to malaria elimination, the WHO has recommended multiple first line treatments i.e., simultaneous use of several artemisinin-based combinations. Artesunate amodiaquine (ASAQ) is a clear choice for inclusion but there is currently no child-friendly formulation. Taste mask coated ASAQ micro pellets (MPs) have been developed using a patented technology, MicroCoatTM. They are palatable, easy to administer, offering dosing flexibility and an innovative child-friendly solution. We aim to advance the development of ASAQ_MPs by: (i) performing a field trial in Malawi, and (ii) charting a path to WHO prequalification & commercialisation. GMP quality ASAQ_MP clinical batches will be compared to standard ASAQ tablets in a randomised trial of under-5 children with acute P. falciparum to assess: (i) desethylAQ exposure, 28-day efficacy, tolerability & acceptability (n=39/arm), and (ii) transmission blocking efficacy by direct membrane feeding: ASAQ_MPs vs. ASAQ_MPs + flavoured single-low-dose primaquine (SLDPQ), including PQ & carboxyPQ PK (n=26/arm). If ASAQ MP-tablet desethylAQ exposures are bioequivalent, this will inform ASAQ_MP dosing in a future pivotal bioequivalence study. A robust pathway to impact strategy will: (i) raise awareness of ASAQ_MPs amongst malaria control programmes and key international organisations (e.g., WHO), especially for the under-5 vulnerable group, and (ii) determine how best to achieve WHO prequalification. Manufacturers in Low- and middle-income countries, including those in SSA, will be engaged for future technology transfer and commercialisation of ASAQ_MP. MicroCoatTM innovative technology could also be applied to paediatric HIV and TB.