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ERJ Open Res
. 2023 Oct 2;9(5):00249-2023.
doi: 10.1183/23120541.00249-2023. eCollection 2023 Sep. A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2
Tom Wilkinson 1 , Anthony De Soyza 2 , Miles Carroll 3 , James D Chalmers 4 , Michael G Crooks 5 , Gareth Griffiths 6 7 , Manu Shankar-Hari 8 , Ling-Pei Ho 9 , Alex Horsley 10 , Chris Kell 11 , Beatriz Lara 12 , Biswa Mishra 13 , Rachel Moate 14 , Clive Page 15 , Hitesh Pandya 16 , Jason Raw 17 , Fred Reid 16 , Dinesh Saralaya 18 , Ian C Scott 19 , Salman Siddiqui 20 , Andy Ustianowski 21 , Natalie van Zuydam 22 , Ashley Woodcock 10 23 , Dave Singh 10 23
Affiliations
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.
. 2023 Oct 2;9(5):00249-2023.
doi: 10.1183/23120541.00249-2023. eCollection 2023 Sep. A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2
Tom Wilkinson 1 , Anthony De Soyza 2 , Miles Carroll 3 , James D Chalmers 4 , Michael G Crooks 5 , Gareth Griffiths 6 7 , Manu Shankar-Hari 8 , Ling-Pei Ho 9 , Alex Horsley 10 , Chris Kell 11 , Beatriz Lara 12 , Biswa Mishra 13 , Rachel Moate 14 , Clive Page 15 , Hitesh Pandya 16 , Jason Raw 17 , Fred Reid 16 , Dinesh Saralaya 18 , Ian C Scott 19 , Salman Siddiqui 20 , Andy Ustianowski 21 , Natalie van Zuydam 22 , Ashley Woodcock 10 23 , Dave Singh 10 23
Affiliations
- PMID: 37868151
- PMCID: PMC10588785
- DOI: 10.1183/23120541.00249-2023
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.