With the overarching goal of enabling the World Health Organization's “Road Map for Neglected Tropical Diseases” (2021-2030), eWHORM aims to address key actions necessary to eliminate neglect of filarial and soil-transmitted helminth (STH) infections and improve capacity in endemic countries. These actions include the development of new and more effective treatment options, the advancement of more sensitive diagnostics, and the strengthening of local healthcare systems. To this end, the eWHORM partners will pursue three objectives:
Objective 1: Implementing an adaptive clinical trial platform
Adaptive trial designs expedite drug development, enhance trial efficiency, and improve patient access to medications. Common master protocols offer advantages such as operational harmonisation, addressing multiple questions and efficient resource utilisation. By implementing the same infrastructure for various sub-studies, such as site selection, patient screening, and data management, multiple research inquiries can be explored. Therefore, eWHORM will develop an adaptive basket trial master protocol for the drug candidate oxfendazole targeting several helminth species (pan-nematode). Standardised procedures and comprehensive monitoring systems will be established. A joint electronic case report form and data management platform will harmonise data analysis, allowing for futility analysis and examination of geographical variations in drug efficacy. This data-driven approach enables trial modifications before reaching the sample size, avoiding statistical power issues.
Objective 2: Testing OXF for its PoC in helminth-infected patients
Oxfendazole (OXF), an advanced compound investigated within the EU-funded HELP project, has shown good human safety in recent clinical trials, making it a potential anthelmintic treatment for filarial and soil-transmitted helminths (STH). The recent bioavailability trial of the OXF tablet formulation provided the expected exposure results. By developing an adaptive trial design, eWHORM aims to progress OXF into a proof-of-concept (PoC) trial to expand treatment options for helminth-infected patients and support future registration of OXF. Recruitment will focus on specific diseases at each Sub-Saharan Africa (SSA) partner site: onchocerciasis (the Democratic Republic of the Congo), loiasis (the Gabonese Republic), mansonellosis (the Republic of Cameroon), and trichuriasis (the United Republic of Tanzania). Co-infected individuals across all trial sites will also be considered. The clinical trial facilities are well established and equipped with pharmacy, laboratory and emergency medical resources. This initiative enhances knowledge and capacity for adaptive trials across different sites, strengthening local preparedness for global health threats in remote areas.
Objective 3: Building capacity for adaptive clinical trial conduct and improving diagnostic capability for parasite infections
Laboratories in low- and middle-income countries (LMICs) suffer from chronic underinvestment, resulting in inadequate infrastructure, limited technical staff, insufficient assistance, and a lack of appropriate diagnostic tools. Despite these challenges, laboratories play a vital role in addressing Neglected Tropical Diseases (NTDs), infectious diseases such as COVID-19, Ebola, and Marburg, as well as monitoring drug resistance. By improving laboratory infrastructure through further investments, eWHORM will improve the diagnosis of multiple diseases and the implementation of molecular biology techniques for different diseases. A virtual training and assessment tool will be established to identify filarial and parasitic infections using microscopy and train the local staff. These initiatives complement existing investments in clinical trial sites, fostering knowledge exchange among LMIC partners. Scientists in LMICs will benefit from development opportunities, including training in clinical trial conduct, workshops on research aspects, data management, and communication. A mentoring program, along with a Master and PhD programme, will support early career researchers and promote gender equality in science and clinical research.