TY - JOUR T1 - Phase 3 RCT of C5a-Specific Vilobelimab in Severe COVID-19 Pneumonia JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2022.4725 VL - 60 IS - suppl 66 SP - 4725 AU - A P Vlaar AU - G Hermans AU - M Witzenrath AU - P Van Paassen AU - L Heunks AU - B Mourvillier AU - S De Bruin AU - E L Lim AU - M Piagnerelli AU - A Roquilly AU - J Lascarrou AU - M Bauer AU - C Schwebel AU - M Brouwer AU - P Tuinman AU - T Welte AU - G Marx AU - U Jaschinski AU - A Cornet AU - A Grebenyuk AU - P Jorens AU - S Rückinger AU - K Pilz AU - C Thielert AU - D Neukirchen AU - L Ruckerbauer AU - B Burnett AU - R Guo AU - D Van De Beek AU - N Riedemann Y1 - 2022/09/04 UR - http://erj.ersjournals.com/content/60/suppl_66/4725.abstract N2 - Background: Blocking the C5a-C5aR axis in COVID-19 patients could improve outcomes by limiting myeloid cell infiltration in damaged organs and preventing excessive lung inflammation and endothelialitis.Aims and Objectives: Vilobelimab (VILO), an anti-C5a mAb that preserves the membrane attack complex (MAC), was tested in a Phase III adaptively designed multicenter, double-blind placebo (P)-controlled study for survival in critically ill COVID-19 patients.Methods: COVID-19 pneumonia patients (N=369; VILO n=178, P n=191) within 48 hrs of intubation were randomly assigned to receive 6, 800 mg infusions of VILO or P on top of standard of care. Primary outcome was 28-day all-cause mortality.Results: 28-day all-cause mortality was 31.7% VILO vs 41.6% P (Kaplan-Meier estimates; Cox regression site stratified, HR 0.73; 95%CI:0.50-1.06; P=0.094) with a 22.7% relative mortality reduction to Day 60. In predefined primary outcome analysis without site stratification, VILO significantly reduced 28-day mortality (HR 0.67; 95%CI:0.48-0.96; P=0.027); needed to treat number, 10 to save 1. VILO significantly reduced 28-day mortality in severe patients with baseline WHO ordinal scale score of 7 (n=237, HR 0.62; 95%CI:0.40-0.95; P=0.028) or severe ARDS/PaO2/FiO2≤100 mmHg (n=98, HR 0.55; 95%CI:0.30-0.98; P=0.044) or eGFR<60 mL/min/1.73m2 (n=108, HR 0.55; 95%CI:0.31-0.96; P=0.036). Treatment emergent AEs were 90.9% VILO vs 91.0% P. Infections were comparable; VILO (62.9%), P (59.3%). Serious AEs were 58.9% VILO, 63.5% P.Conclusion: VILO reduced mortality at 28 to 60 days in severe COVID-19 pneumonia patients with no increase in infections suggesting the importance of targeting C5a while preserving MAC.FootnotesCite this article as Eur Respir J 2022; 60: Suppl. 66, 4725.This article was presented at the 2022 ERS International Congress, in session “-”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -