As part of a new UK trial researchers at the University of Oxford will investigate whether administering the anti-inflammatory drug infliximab to patients with COVID-19 can prevent progression to respiratory failure or death.
The multi-arm, multi-stage CATALYST Trial, is being led by the University of Birmingham in partnership with University Hospitals Birmingham and the Birmingham NIHR Biomedical Research Centre (BRC). The trial is a collaboration with the NIHR Oxford BRC and University College London NIHR BRC.
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 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 Oxford arm of the study, led by Professor Duncan Richards of the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, and Dr Matt Rowland of the Nuffield Department of Clinical Neurosciences, is funded by UK Research and Innovation with support from the arthritis therapy acceleration programme (A-TAP), University of Oxford Medical Sciences Division COVID fund, and Helena Charitable Foundation.
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, such as 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 University of Oxford.
“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,” Prof Richards, the Oxford BRC’s Co-theme Lead for Musculoskeletal.
“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.”
In another arm of the CATALYST trial, the Oxford-based biopharmaceutical company Izana Bioscience will provide Namilumab (IZN-101), a fully human monoclonal antibody already in late-stage trials to treat rheumatoid arthritis and an inflammatory disease called ankylosing spondylitis.
It targets a ‘cytokine’ called GM-CSF (granulocyte-macrophage colony stimulating factor), which is naturally secreted by immune cells in the body but, in uncontrolled levels, is believed to be a key driver of the excessive and dangerous lung inflammation seen in COVID-19 patients.