Recombinant Human C1 Esterase Inhibitor Treatment in Addition to Standard of Care for the Prevention of Cytokine Storm in Hospitalized Patients with COVID-19: A Randomized, Open-Label Trial

Background: The complement system plays a role in hyperinflammation due to COVID-19, and C1 esterase inhibitor (C1-INH) is a key inhibitor. Recombinant human C1-INH (rhC1-INH) treatment could impact the clinical course by limiting this hyperinflammatory response. This trial evaluated if rhC1-INH + COVID-19 standard of care (SOC) administered early during hospitalization could positively impact the clinical course.Methods: In a phase 2, open-label trial in adults hospitalized with COVID-19, patients were randomized (2:1) to rhC1-INH 50 U/kg (maximum, 4200 U) every 12 hours for 4 days + SOC or SOC alone. The primary endpoint was Day 7 clinical status (World Health Organization scale).Results: Thirty-eight patients (rhC1-INH + SOC [n=27]; SOC alone [n=11]) were included, with a significant difference at Day 7 favoring rhC1-INH + SOC for percentage of patients by clinical status (p=0.002). No patients in rhC1INH + SOC group and 2/11 (18.2%) in SOC alone group were admitted to intensive care unit. In rhC1-INH + SOC group, 26/27 patients (96.3%) had ≥1 level improvement in clinical status versus 8/11 patients (72.7%) in SOC alone group (p = 0.03); no clinical status deterioration was observed in rhC1-INH + SOC group. Interleukin-6 and C-reactive protein levels in rhC1-INH + SOC group remained low versus substantial elevations in SOC alone group. Most common adverse events in rhC1-INH + SOC group included transaminitis, dyspnea, and hypertension. One death occurred in SOC alone group.Conclusion: These data support that early treatment with rhC1INH + SOC provided clinical benefit to hospitalized patients with COVID-19.