A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19 : ACCORD-2
Copyright ©The authors 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
ERJ open research - 9(2023), 5 vom: 19. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wilkinson, Tom [VerfasserIn] |
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| Anmerkungen: |
Date Revised 30.10.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1183/23120541.00249-2023 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM36360460X |
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| 100 | 1 | |a Wilkinson, Tom |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19 |b ACCORD-2 |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 30.10.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Copyright ©The authors 2023. | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a De Soyza, Anthony |e verfasserin |4 aut | |
| 700 | 1 | |a Carroll, Miles |e verfasserin |4 aut | |
| 700 | 1 | |a Chalmers, James D |e verfasserin |4 aut | |
| 700 | 1 | |a Crooks, Michael G |e verfasserin |4 aut | |
| 700 | 1 | |a Griffiths, Gareth |e verfasserin |4 aut | |
| 700 | 1 | |a Shankar-Hari, Manu |e verfasserin |4 aut | |
| 700 | 1 | |a Ho, Ling-Pei |e verfasserin |4 aut | |
| 700 | 1 | |a Horsley, Alex |e verfasserin |4 aut | |
| 700 | 1 | |a Kell, Chris |e verfasserin |4 aut | |
| 700 | 1 | |a Lara, Beatriz |e verfasserin |4 aut | |
| 700 | 1 | |a Mishra, Biswa |e verfasserin |4 aut | |
| 700 | 1 | |a Moate, Rachel |e verfasserin |4 aut | |
| 700 | 1 | |a Page, Clive |e verfasserin |4 aut | |
| 700 | 1 | |a Pandya, Hitesh |e verfasserin |4 aut | |
| 700 | 1 | |a Raw, Jason |e verfasserin |4 aut | |
| 700 | 1 | |a Reid, Fred |e verfasserin |4 aut | |
| 700 | 1 | |a Saralaya, Dinesh |e verfasserin |4 aut | |
| 700 | 1 | |a Scott, Ian C |e verfasserin |4 aut | |
| 700 | 1 | |a Siddiqui, Salman |e verfasserin |4 aut | |
| 700 | 1 | |a Ustianowski, Andy |e verfasserin |4 aut | |
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| 700 | 1 | |a Woodcock, Ashley |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Dave |e verfasserin |4 aut | |
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