A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR).
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Patel Jatin, Bass Damon, Beishuizen Albertus, Bocca Ruiz Xavier, Boughanmi Hatem, Cahn Anthony, Colombo Hugo, Criner Gerard J, Davy Katherine, de-Miguel-Díez Javier, Doreski Pablo A, Fernandes Sofia, François Bruno, Gupta Anubha, Hanrott Kate, Hatlen Timothy, Inman Dave, Isaacs John D, 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, O'Shea Ciara, Plantefeve Gaëtan, Schifano Lorrie, Schwab Lee E, Shahid Zainab, Shirano Michinori, Smith Julia E, Sprinz Eduardo, Summers Charlotte, Terzi Nicolas, Tidswell Mark A, Trefilova Yuliya, Williamson Russell, Wyncoll Duncan, Layton Mark
Аннотация
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.