Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial.

Primary endpoint The improvement in PaO 2 /FiO 2 from baseline to day 6 had a least square mean (LSmean) change of 56.4 mmHg (95% CI 31.9 to 80.9) in the zilucoplan group and 20.6 mmHg (95% CI − 17.3 to 58.5) in the control group, corresponding to a difference between groups of 35.8 mmHg, which failed to reach statistical significance (95% CI − 9.4 to 80.9; p = 0.12) (Fig. 2 and Additional file 7 : Table S1).

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Indeed, two large trials of anaphylatoxin C5a antibody are ongoing ( NCT04333420 ; NCT04449588 ), one having reported favorable interim results with a positive trend on survival [ 44 ].

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What this study adds: While the improved oxygenation upon C5 blockade did not reach statistical significance, a Bayesian approach suggested that COVID-19 patients with hypoxia and systemic inflammation on zilucoplan had a 89% chance to fare better.

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