SCIL-COV19 PK/PD trial [COVID-19]
Research type
Research Study
Full title
Subcutaneous and Intravenous anakinra in COVID-19 Infection - Feasibility & Pharmacokinetics/ Pharmacodynamics study
IRAS ID
282110
Contact name
Timothy Felton
Contact email
Sponsor organisation
University of Manchester
Eudract number
2020-001636-95
Duration of Study in the UK
0 years, 3 months, 21 days
Research summary
Research Summary
We plan a small trial of an existing drug in patients with COVID-19 at Salford Royal NHS Foundation Trust (SRFT) and Manchester Foundation Trust (MFT). We will recruit patients with suspected or confirmed COVID-19 infection within 24 hours of being transfer in a Critical Care department. \n\nOur group have been testing interleukin-1 receptor antagonist: IL-1Ra (known as Anakinra) for many years. Marketed as a treatment for rheumatoid arthritis and for some rare autoimmune diseases, we have shown Anakinra also reduces or blocks inflammation in a number of other conditions e.g. stroke and brain haemorrhage. We have found it to be safe, easily administered and well tolerated. \n\nAs part of the global response to the SARS-COV-2 pandemic, researchers have identified drugs that repurposing existing drugs. Anakinra has been proposed as a candidate therapy for COVID-19 and will be used in REMAP-CAP clinical trial as an intravenous (IV) therapy four times daily (qds). Whilst there is uncertainty about the therapeutic benefits, we wish to explore the theory that we can achieve the same concentrations in the blood using a subcutaneous (SC) injection twice daily (bd), as observed with IV therapy qds. \n\nWe will randomise up to 40 patients to receive either SC Anakinra twice daily or IV Anakinra four-times daily for 14 days (or until discharge from CCU). We will measure changes in biomarkers in both groups and use the data to inform a mathematical model to simulate the effect the drug may have on the body. Our aim is to the provide evidence that a lower dose SC Anakinra is as effective as higher dose IV. \n [Study relying on COPI notice]
Summary of Results
Recruitment was paused between waves of the COVID19 pandemic in December 2020 as there were no eligible participants. The trial was closed early when the REMAP-CAP trial (https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbVDknLRlk3r9Y0tfvaGiBUDbwiDpf99N0bvwWSj9y-2FJijUgWG-2FMsG2c5-2FVrRyRfAVh5Y40MQTR1ABG-2FGBo462ZU-3DcUy5_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKhGMfj7hohxxhvLqmTnjHiRlaTmcBLY7wH7UlVT7SK0DltfIytV9-2Fh-2FKrATz9m6qFpjkzAkUN2HzdEKuxJDwScEn6pDI7vP9vd2HBQVpBV-2Fw368e9-2B7UhNh33ZxvxqmBlT-2B8wU5C-2BEbUkmYB517W1YzSBAhgZxpiFxzIeoS9JhLQ-3D-3D&data=04%7C01%7Capprovals%40hra.nhs.uk%7Ce6e08e597632445f971108d9f5f67c12%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637811261251957974%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000&sdata=PHHks370DDG5SAbEPuBywi0NXbE%2BFZTGcMnWKwYPrko%3D&reserved=0 showed that anakinra was not an effective treatment for COVID19.
Five participants were enrolled. Three participants were given anakinra via the subcutaneous route and two participants were given anakinra via the intravenous route. Two women and three men took part in the trial with an ages ranging from 51 to 68. Two participants completed 14 days of treatment while three participants finished treatment early (on days 4, 5 and 8) when they were discharged from the intensive care unit.
Anakinra was measurable in the blood of participants following both intravenous and subcutaneous administration. The blood concentration of anakinra was similar with either route of administration. Following administration of anakinra there was variability between the levels in blood anakinra levels. Interleukin-6 levels appeared to drop following administration of anakinra. There was insufficient data to perform any more detailed analysis.REC name
North East - Newcastle & North Tyneside 1 Research Ethics Committee
REC reference
20/NE/0140
Date of REC Opinion
20 May 2020
REC opinion
Further Information Favourable Opinion