Prospective, Randomized, Parallel-Group, Open-Label Study to Evaluate the Effectiveness and Safety of IMU-838, in Combination with oseltamivir, in Adults with Coronavirus-19- a feasibility trial

BackgroundThe global urgency for effective treatments against SARS-CoV-2 infections, causing COVID-19, remains paramount. One promising avenue is repurposing existing medications. IMU-838, a dihydroorotate dehydrogenase (DHODH) inhibitor, has exhibited potent antiviral effects against respiratory viruses. In rodent studies, its combined administration with oseltamivir has shown therapeutic potential against both influenza and SARS-CoV-2. ObjectiveThe primary aim of the IONIC pilot feasibility trial was to comprehensively explore the feasibility and safety challenges associated with administering the novel treatment regimen of IMU-838 combined with oseltamivir to COVID-19 patients. The secondary objective was to evaluate whether a 14-day treatment course with IMU-838 and oseltamivir improves time to clinical improvement compared to oseltamivir alone, defined as the duration from randomization to achieving a 2-point improvement on the WHO ordinal scale, discharge from the hospital, or occurrence of death, whichever comes first. MethodsIONIC was a Phase IIb, randomised, open-label, single centre trial. Prospective participants were recruited from a single centre within the UK and were eligible if they had moderate to severe COVID-19 requiring hospitalisation, were aged 18 years or above. Patients were randomly assigned, in a 1:1 ratio, to either the IONIC intervention arm (IMU-838 + oseltamivir + standard care) or the control arm (oseltamivir + standard care). Sponsored by the University Hospital Coventry & Warwickshire NHS Trust and funded by LifeArc, the trial comprises two distinct phases: a pilot feasibility study and a main study. The aim of the feasibility study was to inform the design and execution of the main study. However, due to recruitment challenges, the main study was not conducted. The present paper reports the results of the feasibility study. The trial was prospectively registered with ISRCTN (ISRCTN53038326) and Clinicaltrials.gov (NCT04516915) FindingsBetween 22 Jun 2020 and 20th May 2022, 38 participants were recruited into the trial. Recruitment challenges hindered the main study, but the feasibility trial provided encouraging findings. Treatment completion rates stood at 84%, with no serious adverse effects observed affirming the safety profile of the novel treatment. Although no statistically significant difference emerged in time to clinical improvement between the treatment and control groups, logistic regression analysis indicated a notable association between the treatment group and clinical improvement within a 14-day window. These results emphasize the crucial role of feasibility studies in guiding larger-scale trials and underscore the necessity for further investigation into the therapeutic potential of this approach to the treatment of COVID-19.