In some patients, COVID-19 can progress to severe respiratory failure requiring admission to an intensive care unit and mechanical ventilation of the lungs. This does not occur immediately but seems to progress over 7-10 days after first developing symptoms of the disease.
The overall aim of the CATALYST Trial, one of four National platform trials in the UK, is to guide the selection of new drug interventions for large phase III trials in hospitalised patients with COVID-19 infection. It is hoped that by using drugs that target the most serious symptoms of the virus, the severity of the disease could be mitigated, leading to a reduction in the number of patients needing to be admitted to intensive care and ultimately, a reduction in virus-related deaths.
The University of Birmingham Inflammation and Advanced Cellular Therapy Trials unit is leading the delivery of the trial in partnership with University Hospitals Birmingham and the Birmingham National Institute for Health Research Biomedical Research Centre (BRC). The trial is a collaboration with the NIHR Oxford BRC and University College London NIHR BRC.
The Oxford arm of the study, led by Professor Duncan Richards (NDORMS) and Dr Matt Rowland (Nuffield Department of Clinical Neurosciences), is funded by UK Research and Innovation as well as the University of Oxford Medical Sciences Division COVID fund, and Helena Charitable Foundation. Both arms of the study are being supported by A-TAP.
Director of Clinical Research at the Kennedy Institute, Professor Christopher Buckley, who leads A-TAP said “This is a real example of team science at its best. It is wonderful to see how teams of scientists and clinicians that have never worked together before have coalesced so quickly to deliver a very exciting trial design. This approach of breaking down silos across disciplines and between Universities and their NHS Trusts lies at the heart of the A-TAP philosophy”
Infliximab (CT-P13), produced by Slough based Celltrion Healthcare UK, is an anti-tumour necrosis factor (TNF) therapy that is designed to attach to a protein involved in inflammation. It is currently used as a treatment for conditions including rheumatoid arthritis and inflammatory bowel syndrome under the trade name Remsima®. The Oxford researchers will explore exactly how this drug works to reduce inflammation caused by COVID-19 by taking blood and other samples from critically unwell patients.
The effect of the drug will be measured by the amount of oxygen required by patients as well as assessment of other severity indicators of the disease (i.e organ failure). Drugs in the CATALYST Trial that show efficacy in these measures will be recommended for further testing within large ongoing national trials.
‘We hope that by using a treatment that is already used to treat inflammation in other autoimmune conditions we may be able to manage inflammation associated with COVID-19 early’, said Sir Marc Feldmann, Professor of Immunology at the Kennedy Institute.
‘The study will recruit across Birmingham and Oxford initially but we expect that other centres will join the study soon. We are collaborating closely with Birmingham on the plans for analysis of complex biomarkers. We believe these will provide important mechanistic insights into the drugs in the study and are an important aspect of the clinical and scientific value of this study.’
The A-TAP is funded by the Kennedy Trust for Rheumatology Research.