From M19 to M36, the eWHORM project made substantial progress toward strengthening adaptive clinical trial infrastructure for helminth diseases in sub-Saharan Africa. Key achievements included finalisation and amendment of the harmonised master protocol, establishment and operationalisation of the shared clinical trial database and randomisation systems, and successful initiation of clinical trial activities across Tanzania, Gabon, DRC, and Cameroon. Recruitment and treatment were completed for the trichuriasis sub-study in Tanzania, while enrolment and follow-up for the filarial sub-studies progressed in Gabon, DRC, and Cameroon despite delays caused by regulatory approvals, a temporary safety signal review, and political unrest in Cameroon. Thus, in the coming months we will be able to communicate the first major outcome of this study, the efficacy of oxfendazole on trichuriasis. Importantly, no drug-related severe adverse events were reported with more than 300 participants treated so far. The consortium has advanced highly sensitive LAMP diagnostic assays for filarial and soil-transmitted helminth infections, is in the progress of developing a virtual microscopy training platform, and expanded capacity-building activities through workshops on clinical trial conduct, grant writing, mentorship programmes, MSc and PhD training, and clinical trial support initiatives. Dissemination and exploitation activities intensified through publications, workshops, communication campaigns, and the establishment of an External Advisory Board, while project management structures ensured coordination, risk mitigation, and continued alignment with project objectives to keep delays of the trial as short as possible. Key learnings in conducting an adaptive clinical trial such as eWHORM are that the complexity of the master protocol, especially if run in four distinct countries, present unprecedented challenges for the trial sites and associated partners, as they have to align local procedures with a unified overarching framework. Furthermore, regulatory bodies lack familiarity with adaptive designs, necessitating intensive engagement. In this context, obtaining the European Medicines Agency (EMA) scientific advice for the master protocol provided a strategic advantage. In addition, statistical analysis for adaptive clinical trials, especially if four different diseases are tackled, are complex, require advanced biostatistical expertise and intensive preparation. Finally, logistic challenges exist, as e.g. following the interim analysis and dose selection, both the availability and time-critical distribution of the investigational medicinal product (IMP) to the respective sites is required. Mitigation of these challenges relies entirely on a highly collaborative consortium of trusted partners, leveraging specialized expertise and robust management structures to provide mutual support and successful completion of the project.
