A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2

Wilkinson, Tom; De Soyza, Anthony; Carroll, Miles; Chalmers, James D.; Crooks, Michael G.; Griffiths, Gareth; Shankar-Hari, Manu; Ho, Ling Pei; Horsley, Alex; Kell, Chris; Lara, Beatriz; Mishra, Biswa; Moate, Rachel; Page, Clive; Pandya, Hitesh; Raw, Jason; Reid, Fred; Saralaya, Dinesh; Scott, Ian C.; Siddiqui, Salman; Ustianowski, Andy; van Zuydam, Natalie; Woodcock, Ashley; Singh, Dave; on behalf of The ACCORD Collaborative Group

Abstract

Background Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95). Methods ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19. Patients were randomised 1:1 to tozorakimab 300 mg plus standard of care (SoC) or SoC alone. The primary end-point was time to clinical response (sustained clinical improvement of ⩾2 points on the World Health Organization ordinal scale, discharge from hospital or fit for discharge) by day 29. Other end-points included death or respiratory failure, mortality and intensive care unit admission by day 29, and safety. Serum IL-33/soluble stimulated-2 (sST2) complex levels were measured by high-sensitivity immunoassay. Results Efficacy analyses included 97 patients (tozorakimab+SoC, n=53; SoC, n=44). Median time to clinical response did not differ between the tozorakimab and SoC arms (8.0 and 9.5 days, respectively; HR 0.96, 80% CI 0.70–1.31; one-sided p=0.33). Tozorakimab was well tolerated and the OR for risk of death or respiratory failure with treatment versus SoC was 0.55 (80% CI 0.27–1.12; p=0.26), while the OR was 0.31 (80% CI 0.09–1.06) in patents with high baseline serum IL-33/sST2 complex levels. Conclusions Overall, ACCORD-2 results suggest that tozorakimab could be a novel therapy for patients hospitalised with COVID-19, warranting further investigation in confirmatory phase 3 studies.

Citation

Wilkinson, T., De Soyza, A., Carroll, M., Chalmers, J. D., Crooks, M. G., Griffiths, G., Shankar-Hari, M., Ho, L. P., Horsley, A., Kell, C., Lara, B., Mishra, B., Moate, R., Page, C., Pandya, H., Raw, J., Reid, F., Saralaya, D., Scott, I. C., Siddiqui, S., …on behalf of The ACCORD Collaborative Group. (2023). A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2. ERJ Open Research, 9(5), Article 00249-2023. https://doi.org/10.1183/23120541.00249-2023

• Journal Article Type: Article
• Acceptance Date: Jul 25, 2023
• Online Publication Date: Aug 9, 2023
• Publication Date: Sep 1, 2023
• Deposit Date: Oct 15, 2024
• Publicly Available Date: Oct 21, 2024
• Journal: ERJ Open Research
• Electronic ISSN: 2312-0541
• Publisher: European Respiratory Society
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 5
• Article Number: 00249-2023
• DOI: https://doi.org/10.1183/23120541.00249-2023
• Public URL: https://hull-repository.worktribe.com/output/4445042