EMINENCE · Eliminating onchocerciasis with Moxidectin in endemic hotspots of Central Africa

Onchocerciasis is a neglected tropical disease leading to blindness and associated with epilepsy. Most cases are in sub-Saharan Africa. The WHO has proposed that its transmission be interrupted in a third of endemic countries by 2030. The main strategy is annual Community-Directed Treatment with Ivermectin (CDTI). Despite nearly 3 decades of CDTI, transmission persists in several foci. In Phase II & III clinical trials, moxidectin has shown superior efficacy compared to ivermectin, clearing Onchocerca volvulus microfilariae for nearly a year. No large-scale community trials have yet been undertaken to document its effectiveness and safety for mass treatment. A barrier to onchocerciasis elimination is its co-endemicity with loiasis in Central Africa. Individuals with high Loa loa microfilaraemia may develop serious adverse events if treated with ivermectin. EMINENCE will address these challenges through: 1) a Phase IIIb community trial of annual or biannual moxidectin compared to annual ivermectin in Bafia and Monatele, Cameroon, renowned for their high transmission intensity, 2) a Phase II adaptive trial of ascending moxidectin doses on increasing L. loa microfilarial densities, and 3) a social sciences study to assess the acceptability of and adherence to moxidectin. We will evaluate and model the epidemiological impact of annual or biannual moxidectin compared to annual ivermectin through parasitological, serological and entomological surveys, and will attempt to elucidate potential differences between the two drugs regarding their effects on adult worms. We will evaluate the safety, tolerability and efficacy of moxidectin compared to ivermectin in L. loa-infected individuals in the Republic of Congo and Cameroon. Our project will contribute to the evidence-base that moxidectin may be effective and cost-effective to accelerate onchocerciasis elimination in areas where ivermectin has proved insufficient, and will investigate its safety in loiasis co-endemic areas.