RESULTS: From Oct 1, 2020 to Oct 4, 2021, 368 invasively mechanically ventilated COVID-19 patients were randomized: 177 patients were randomly assigned to receive
vilobelimab while 191 patients received placebo. Pharmacokinetic sampling was only performed at sites in Western Europe. Blood samples for
vilobelimab measurements were available for 93 of 177 (53%) patients in the
vilobelimab group and 99 of 191 (52%) patients in the placebo group. On day 8, after three infusions, mean
vilobelimab (trough) concentrations ranged from 21,799.3 to 302,972.1 ng/mL (geometric mean 137,881.3 ng/mL). Blood samples for C5a measurements were available for 94 of 177 (53%) patients in the
vilobelimab group and 99 of 191 (52%) patients in the placebo group. At screening, C5a levels were highly elevated and comparable between groups. In the
vilobelimab group, median C5a levels were 118.3 ng/mL [IQR 71.2-168.2 ng/mL] and in the placebo group, median C5a levels were 104.6 ng/mL [IQR 77.5-156.6 ng/mL]. By day 8, median C5a levels were reduced by 87% in the
vilobelimab group (median 14.5 ng/mL [IQR 9.5-21.0 ng/mL], p < 0.001) versus an 11% increase in the placebo group (median 119.2 ng/mL [IQR 85.9-152.1 ng/mL]). Beyond day 8, though plasma sampling was sparse, C5a levels did not reach screening levels in the
vilobelimab group while C5a levels remained elevated in the placebo group. Treatment-emergent ADAs were observed in one patient in the
vilobelimab group at hospital discharge on day 40 and in one patient in the placebo group at hospital discharge on day 25.
CONCLUSIONS: This analysis shows that
vilobelimab efficiently inhibits C5a in
critically ill COVID-19 patients. There was no evidence of immunogenicity associated with
vilobelimab treatment. Trial registration ClinicalTrials.gov, NCT04333420. Registered 3 April 2020, https://clinicaltrials.gov/ct2/show/NCT04333420.