the platform adaptive randomised trial for new and repurposed filovirus treatments (partners) trial

Aim This project aims to improve survival in patients infected with Ebola and related viruses (filoviruses). It will do this by establishing the Platform Adaptive Randomised Trial for NEw and Repurposed Filovirus treatmentS (PARTNERS) trial, a multi-country, multi-outbreak clinical trial. This initiative will be achieved through a World Health Organization (WHO) partnership involving governments and academic institutions in Africa, and specialists in clinical trials for outbreak-prone diseases.   Global challenge of filovirus outbreaks Filoviruses frequently cause outbreaks in Africa, particularly in countries classified by the United Nations as 'least developed' (LDCs). The most well-known of these viruses - Ebola and Marburg - cause severe disease with fatality rates of 60-90%?(1). The west Africa outbreak killed over 11,000 people, with an average age of 32 at death. Mortality is especially high amongst pregnant women, newborns, and children?(1). Healthcare workers are also disproportionately affected(1)?, which further worsens healthcare deficiencies in affected countries. The social and economic consequences can be devastating. For example, during the west Africa outbreak, prolonged school closures (9 months) led to school drop out of 17,400 secondary schoolchildren, mostly from the poorest families(2)?.? In each of the three most affected countries, several hundred thousand people were made severely food insecure, with women, who often rely on social and informal economies, bearing the brunt of the impact(3,4). Data from the 2022-3 Uganda outbreak suggests that access to healthcare, clean water, food, education, and livelihoods are adversely impacted even in smaller outbreaks(5)?. Providing access to safe and effective treatments is a crucial aspect of outbreak response.   Context Despite substantial investment in the pre-clinical development of new treatments, clinical evaluation during filovirus outbreaks has been limited. The research response has faced two critical challenges: Slow Initiation of Clinical Trials: Previous trials were initiated only after an outbreak started and were designed specifically for that outbreak. The time required for design, approvals, and enrolment is too slow relative to an outbreak's duration. PARTNERS will be the first trial to encompass all filovirus subtypes and will be pre-positioned in multiple high-risk countries, allowing rapid activation at the onset of an outbreak. It will also be the first trial to enable data accumulation across multiple small outbreaks, thereby maximising the potential for definitive findings on drug safety and efficacy across filovirus diseases.  Limited Evaluation of Treatments: Previous trials evaluated only a small number of potential treatments. PARTNERS will define multiple "therapeutic domains," enabling the simultaneous assessment of different treatment approaches, including filovirus-specific drugs (e.g., monoclonal antibodies), broad-acting antivirals (e.g., remdesivir), and drugs targeting host-responses (e.g., corticosteroids).    Application and benefits The funding will be used to design, approve, and launch the PARTNERS trial in three leading countries who are at risk for filovirus outbreaks. The expected benefits include: Improved Care and Outcomes: Enhancing the treatment and survival rates of patients with filoviruses.  Enhanced Outbreak Control: Boosting confidence in care, thereby improving outbreak management.  Strengthened Regional Capacity: Building and coordinating regional capacity for conducting phase III clinical trials.  The innovative design of this trial, aimed at producing actionable evidence in challenging circumstances, can be applied to other infectious disease challenges in the region.