A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR).

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.

• Authors: Jatin Patel, Damon Bass, Albertus Beishuizen, Xavier Bocca Ruiz, Hatem Boughanmi, Anthony Cahn, Hugo Colombo, Gerard J Criner, Katherine Davy, Javier de-Miguel-Díez, Pablo A Doreski, Sofia Fernandes, Bruno François, Anubha Gupta, Kate Hanrott, Timothy Hatlen, Dave Inman, John D Isaacs, Emily Jarvis, Natalia Kostina, Tatiana Kropotina, Jean-Claude Lacherade, Divya Lakshminarayanan, Pedro Martinez-Ayala, Charlene McEvoy, Ferhat Meziani, Mehran Monchi, Sumanta Mukherjee, Rosana Muñoz-Bermúdez, Jessica Neisen, Ciara O'Shea, Gaëtan Plantefeve, Lorrie Schifano, Lee E Schwab, Zainab Shahid, Michinori Shirano, Julia E Smith, Eduardo Sprinz, Charlotte Summers, Nicolas Terzi, Mark A Tidswell, Yuliya Trefilova, Russell Williamson, Duncan Wyncoll, Mark Layton
• Journal: The European respiratory journal (Eur Respir J) Vol. 61 Issue 2 (02 2023) ISSN: 1399-3003 [Electronic] England
• PMID: 36229048 (Publication Type: Randomized Controlled Trial, Multicenter Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright ©The authors 2023.

Chemical References

• Granulocyte-Macrophage Colony-Stimulating Factor
• Otilimab
• Antibodies, Monoclonal, Humanized

Topics

• Adult
• Humans
• COVID-19
• Granulocyte-Macrophage Colony-Stimulating Factor
• Antibodies, Monoclonal, Humanized
• Respiratory Insufficiency
• Double-Blind Method
• Treatment Outcome