FAME · REPURPOSING FUSIDIC ACID AS A SHORT-COURSE ONCHOCERCA VOLVULUS MACROFILARICIDE: A RANDOMIZED CONTROLLED OPEN-LABEL PARALLEL GROUP INTERVENTION PHASE IIA/B PILOT TRIAL

Onchocerciasis (river blindness) is a vector-borne, filarial nematode neglected tropical disease (NTD), affecting an estimated 21 million individuals, 99% of which reside within 31 Sub-Saharan African countries. Approximately 14.6 million onchocerciasis infected individuals suffer skin disease and 1.15 million are visually impaired.Onchocerciasis is prioritized for elimination as a public health problem by The World Health Organisation with ambitious targets set as part of the NTDs Roadmap to 2030. To enable elimination targets from 2030 onwards, WHO and major stakeholders, including funders and product development partners, recognize that a new short-course curative (macrofilaricide) treatment is required (or a short-course agent which permanently blocks parasite reproduction and transmission), as well as a safe alternative strategy to eliminate onchocerciasis where the related filaria, Loa loa is co-endemic in Central Africa.We have pre-clinical data from efficacy screens and pharmacokinetic-pharmacodynamic modelling that positions the registered antibiotic, fusidic acid (FA) at the late laboratory validation stage as a potential seven day macrofilaricide drug cure, via targeting the Onchocerca filarial symbiont, Wolbachia.We propose to advance FA into clinical testing. We will undertake dose ranging to assess FA systemic exposures and safety in a Cameroonian onchocerciasis target population aligned with acceptable delivery (once, or twice daily dosing, maximum 14 days). We will establish exploratory efficacy proof-of-concept utilising early endpoint indicators of Wolbachia depletions within female O. volvulus and impact on embryogenesis compared against a 4-week doxycycline gold-standard treatment comparator, six months post-treatment. The major output of FAME will be to develop a development plan of clinical safety, pharmacology, pilot efficacy and market access scoping for entry into phase II trials on a pathway toward registering a new onchocerciasis cure.