Eliminating worm infectionsin sub-saharan africa and enabling the who's road map 2021-2030

1 Year of eWHORM: Exploring Achievements and Hopes in the Fight against NTDs in Conversation with Marc Hübner

On its first anniversary, eWHORM celebrates a year of remarkable progress. On World Health Day last year, we were excited to launch our project and start our mission to eliminate worm infections in Sub-Saharan Africa. Now, one year later, we had the opportunity to sit down with our coordinator, Prof. Marc Hübner from University Hospital Bonn, to explore the project achievements made in the past months and gain insights into the work ahead.

It has been a year since the launch of eWHORM. How is the project progressing?

We had an excellent start with our eWHORM project, and I am happy to say that it is well on track. During our kick-off meeting in Bonn one year ago, we had the chance to meet all collaboration partners and strengthen the collaboration between partners with different expertise. Our partners have knowledge of different tropical helminth diseases, clinical trials in different African countries, complex statistics within an adaptive clinical trial, diagnostic tools for parasitic diseases, and the establishment of a virtual training and assessment tool for parasitic diseases diagnosis. These complimentary skills allowed us to prepare an adaptive basket trial to assess the efficacy of the pan-nematode drug candidate oxfendazole to treat the filarial diseases onchocerciasis, loiasis and mansonellosis as well as the intestinal helminth infection trichuriasis in four different sub-Saharan African countries, namely Gabon, the Democratic Republic of the Congo, Cameroon and Tanzania. Furthermore, preparations to improve diagnostics, train & mentor early career scientists, and improve clinical trial expertise were made. Our eWHORM project has already been presented by several partners at national and international conferences as well as on professional and social media channels.

The project aims to establish an adaptive clinical trial platform and enhance clinical research infrastructure for NTDs in four SSA countries. Are there any achievements in this direction that you can already share with us?

Within the first year, we took the essential steps that will allow us to perform a phase 2, multi-country, randomised, placebo-controlled, double-blinded adaptive platform trial to assess the efficacy and safety of oxfendazole in adults with trichuriasis, mansonellosis, onchocerciasis and/or loiasis. As complicated as the title of the eWHORM basket trial are the details to conduct such a complex clinical trial. Our statistic experts from the Medical University of Vienna performed data simulations, which helped to design the adaptive clinical trial and prepared a statistical analysis plan, which will be used for interim analyses and adaption of the clinical study based on efficacy and safety. DNDi, INRB, Swiss TPH, CERMEL, BNITM, University of Buea, UKB and MUW combined their expertise to prepare a master protocol to harmonize the procedures of the clinical trial. Additionally, a briefing document was submitted to the European Medicines Agency for advice on the adequacy of the proposed basket trial design and the statistical considerations. Oxfendazole, our pan-nematode drug candidate, as well as placebo tablets, are currently being produced and will soon be available.
In terms of diagnostics, our partner EMC already presented an early version of a virtual microscopy training tool for technicians, doctors and scientists in our African partner countries to identify parasites in blood. In addition, at the end of April, our partners from the University of Buea will host a LAMP assay workshop to train our African partners to detect different filarial and intestinal helminth species using this field-applicable, highly sensitive, and specific method. Importantly, a mentorship programme to guide and support the careers of African scientists as well as a MSc and PhD programme was initiated under the lead of BNITM. Last but not least, a big thanks to EURICE, who is able to keep all researchers and projects on track and support the communication of our project results. Based on these essential achievements, we are confident that we can start with the treatment of the first participants within the second year of eWHORM.

What is the expected impact of eWHORM, and who will benefit the most from the project results?

Parasitic helminth infections can cause debilitating diseases such as river blindness (onchocerciasis), loiasis (African eye worm), mansonellosis, or trichuriasis. These diseases can cause blindness and severe dermatitis (onchocerciasis), angioedema, variable unspecific complications and increased mortality (loiasis), delayed child development and anemia (trichuriasis), and impact co-infections and vaccine responses (mansonellosis). Control programmes do exist for the neglected tropical diseases such as onchocerciasis and soil-transmitted helminths, but the drugs used for mass drug administration for onchocerciasis do not kill the adult worms, and drugs used for soil-transmitted helminths have poor efficacy at single-dose against trichuriasis. Furthermore, loiasis and mansonellosis are not listed as neglected tropical diseases by the WHO, and no control programmes do exist. Importantly, in the case of loiasis, drugs that are used for MDA may cause life-threatening adverse events. In the case of mansonellosis, MDA treatment is not efficacious as a single dose. Thus, our overall goal of eWHORM is to provide new treatment options for helminth infections to eliminate filarial and soil-transmitted helminth infections. Within eWHORM, we aim to provide the proof of concept for oxfendazole as an inexpensive and effective drug for multiple helminth diseases that affect hundreds of millions of people in sub-Saharan Africa. In addition, we will build and improve the capacity in endemic countries to perform state-of-the-art clinical trials and diagnostics. We aim to provide improved treatments for those affected by helminth infections and make a long-term impact in endemic countries by enhancing the capacity for persistent and future health challenges.

Looking back at the first year, could you share the challenges you faced and the exciting highlights you experienced?

Our consortium consists of ten partners from seven different countries. While each partner has its specific expertise, it is essential to harmonise the procedures and protocols of our joint basket trial to obtain the best possible data-set to support future registration trials of oxfendazole. Thus, discussions with all partners are essential to deciding on the best possible way forward, which can be challenging. Our kick-off meeting in Bonn helped us to bond as a fantastic team, and the preparation of a joint master protocol and EMA briefing document are the first examples of how we can achieve our ambitious goal.

As we kick off the second year, what hopes and plans do you have as the project coordinator?

Based on the excellent progress we made in the first year, I hope that our project further gains momentum and oxfendazole will be administered, as scheduled, to the first participants. I am strongly convinced that oxfendazole is an excellent pan-nematode drug candidate and hope that already the interim analyses will demonstrate excellent efficacy against onchocerciasis, loiasis, mansonellosis, and trichuriasis. As project coordinator, I am looking forward to attending the LAMP workshop in Cameroon and to the finalisation of the study initiation package so that we can start the clinical trial.