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.

Cameroon

The objective of the Central African engineering schools of the CITAC project is to raise significantly quality standards of their engineering training, implicating actors from society and companies in the conception of adapted curricula to local labour markets.After a first Erasmus+ project called MOSE-FIC on which UCAC was an active member, the CITAC project shifts the leadership to Africa: UCAC will lead the change and brings in three new public and private HEIs from Cameroon and the DRC. As European Quality Standards were chosen as the cornerstone, European experts will provide their experience and insights to the actions decided on from African realities.The activities will lean on the competence-based approach putting the student in the centre of the process (8 curricula reengineered - min. 6 partners of the industrial environment providing insights).Students (3000 directly involved) will benefit from innovative learning methods such as Problem Based Learning, flipped classrooms… Virtual mobility will be supported by the creation of common distance learning activities (200h of e-learning created).Teaching staff (50 concerned-half of them will benefit from mobility) will acquire new know-how in defining learning outcomes and the way to align assessment and course content with them.The governance of the HEIs will be modernised by new rules of continuous enhancement such as assessment of the learning activities by the stakeholders and quality reviews.The local economies will benefit from engineers educated on a strong foundation of scientific and technical skills, combined with personal development work, including engineering ethics and experiences of responsibility in a social context. Thus, these engineers will be able to become leaders for the society, with greater freedom and personal charisma.Finally, for cross-fertilization purposes, the consortium members create and animate a contact cell with all HEIs in the fields of engineering in Central Africa

To target helminth elimination, a drug research and development (R&D) pipeline is needed to provide new chemotherapeutics that effectively eliminate or sterilize adult worms, thus bringing about the paradigm shift necessary to reach the 2030 SDG goals on health. Our consortium proposes to establish a R&D pipeline for anthelminthics targeting nematodes. The focus will be on soil-transmitted helminthiasis and onchocerciasis, since these infections are among the leading neglected tropical diseases. Ground breaking characteristics of the drugs developed within our project are that they will have a unique mechanism of action that, at best, will target multiple nematodes (pan-nematode) with an excellent safety profile, including no efficacy against non-targeted co-endemic species. We will benefit from collaborations with our industrial partners Bayer and Celgene providing preselected compounds to populate the early preclinical stages of the R&D pipeline. Compounds with the best profile will be progressed through preclinical studies. Corallopyronin A, a compound with proven efficacy against essential Wolbachia endosymbionts in filariae that has superiority to the gold standard doxycycline, excellent bioavailability and promising exploratory safety data will undergo state-of-the-art toxicity profiling to advance towards phase 1 trials. We will also evaluate oxfendazol and oxantel pamoate in clinical trials. They have already proven efficacious in animals or humans and will only require clinical trials according to current regulatory guidelines to be implemented. With this strategy, the consortium will ensure that a pipeline of drug candidates is available for treating onchocerciasis, especially should current candidates fail in upcoming clinical trials. Moreover, we will establish a much-needed drug R&D pipeline to treat soil-transmitted helminth infections for which there is currently neither a drug with good efficacy against all species nor any prospects on the horizon.

We will establish for the first time in NTDs an adaptive clinical trial platform and improve clinical research infrastructure in four SSA countries. A drug acting safely on multiple helminths species would be a major leap to tackle NTDs and enable the WHO RoadMap (eWHORM). The cheap and freely-accessible pan-nematode drug oxfendazole (OXF) has such potential. Given the limited portfolio of anthelmintic drug candidates, eWHORM will assess its efficacy in an adaptive clinical trial for simultaneous evaluation against onchocerciasis, loiasis, mansonellosis and trichuriasis. Thus not only the largest group of NTDs, but also diseases that are not (yet) listed will be adressed. This design significantly reduces patient numbers, development time-frames and enables treatment of co-infections. Combined with our highly sensitive molecular tests, we provide a patient-centric approach providing tools for targeted treatment (test and treat) and precision mapping for elimination programs. Strengthening of early career scientists in SSA in all aspects of clinical trial conduct and research including data management, simulation and statistical analysis, will be fostered by introducing a master and PhD program, a mentorship program as well as several webinars. An open-source virtual training and assessment tool for diagnosis of NTDs will complement the knowledge transfer to remote areas in SSA. The consortium encompasses an interdisciplinary partnership from eight different countries (Germany, the Netherlands, Austria, Switzerland, Cameroon, Gabon, Tanzania, and DRC). Each group brings unique knowhow and recognized complementary experience to the project to ensure sustainable capacity building within SSA countries. Through joint development of – and training in – modern, regulatory clinical trial conduct, adaptive clinical trial design and state-of-the-art diagnostics, we will strengthen SSA researchers and clinicians to respond to persisting and future health challenges.