1. A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR).
- Author
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Patel, Jatin, Bass, Damon, Beishuizen, Albertus, Bocca Ruiz, Xavier, Boughanmi, Hatem, Cahn, Anthony, Colombo, Hugo, Criner, Gerard, Davy, Katherine, de-Miguel-Díez, Javier, Doreski, Pablo, Fernandes, Sofia, François, Bruno, Gupta, Anubha, Hanrott, Kate, Hatlen, Timothy, Inman, Dave, Isaacs, John, Jarvis, Emily, Kostina, Natalia, Kropotina, Tatiana, Lacherade, Jean-Claude, Lakshminarayanan, Divya, Martinez-Ayala, Pedro, McEvoy, Charlene, Meziani, Ferhat, Monchi, Mehran, Mukherjee, Sumanta, Muñoz-Bermúdez, Rosana, Neisen, Jessica, OShea, Ciara, Plantefeve, Gaëtan, Schifano, Lorrie, Schwab, Lee, Shahid, Zainab, Shirano, Michinori, Smith, Julia, Sprinz, Eduardo, Summers, Charlotte, Terzi, Nicolas, Tidswell, Mark, Trefilova, Yuliya, Williamson, Russell, Wyncoll, Duncan, and Layton, Mark
- Subjects
Adult ,Humans ,COVID-19 ,Granulocyte-Macrophage Colony-Stimulating Factor ,Antibodies ,Monoclonal ,Humanized ,Respiratory Insufficiency ,Double-Blind Method ,Treatment Outcome - Abstract
BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of COVID-19. METHODS: In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18-79 years (Part 1) or ≥70 years (Part 2) with severe COVID-19, respiratory failure and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90 mg (human anti-GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28. RESULTS: In Part 1 (n=806 randomised 1:1 otilimab:placebo), 71% of otilimab-treated patients were alive and free of respiratory failure at Day 28 versus 67% who received placebo; the model-adjusted difference of 5.3% was not statistically significant (95% CI -0.8-11.4%, p=0.09). A nominally significant model-adjusted difference of 19.1% (95% CI 5.2-33.1%, p=0.009) was observed in the predefined 70-79 years subgroup, but this was not confirmed in Part 2 (n=350 randomised) where the model-adjusted difference was 0.9% (95% CI -9.3-11.2%, p=0.86). Compared with placebo, otilimab resulted in lower serum concentrations of key inflammatory markers, including the putative pharmacodynamic biomarker CC chemokine ligand 17, indicative of GM-CSF pathway blockade. Adverse events were comparable between groups and consistent with severe COVID-19. CONCLUSIONS: There was no significant difference in the proportion of patients alive and free of respiratory failure at Day 28. However, despite the lack of clinical benefit, a reduction in inflammatory markers was observed with otilimab, in addition to an acceptable safety profile.
- Published
- 2023