Table 3.
Summary of Clinical Studies of Complement Inhibition
| Authors | Disease | Study Design | Interventions | Main Findings |
|---|---|---|---|---|
| Fronhoffs 200062 | Streptococcal toxic shock syndrome | Case series N=7 |
C1-esterase inhibitor, 6000 to 10,000 U, within the first 24 hours | Marked reduction in vascular leaks and rapid weaning of vasopressor 6/7 survivors |
| Igonin 201263 | Adults with sepsis | Open-label randomized controlled study N=61 |
C1-esterase inhibitor infusions, 12,000 U | Increased C1-esterase inhibitor functional activity Increased C3 levels Decreased C-reactive protein reduced all-cause mortality (12% vs 45% in control, p = 0.008) |
| Abe 201764 | Sepsis induced coagulopathy with thrombotic microangiopathies | Case report N=1 |
Eculizumab 900 mg once a week for 4 weeks | Rapid weaning of mechanical ventilation and vasopressor, and normalization of renal function |
| Urwyler 202065 | Severe COVID-19 | Case series N=5 |
Human recombinant C1 esterase inhibitor (conestat alfa), 8400 IU followed by 3 additional doses of 4200 IU in 12-h intervals | Rapid improvement in clinical and laboratory markers of inflammation |
| Rambaldi 202066 | COVID-19 ARDS | Case series N=6 Retrospective controls |
Narsoplimab, human immunoglobulin gamma 4 (IgG4) monoclonal antibody against MASP-2 | Rapid decrease in markers of endothelial injury (circulating endothelial cells) and of inflammation (IL-6, IL-8, CRP) |
| Mastaglio 202067 | COVID-19 ARDS | Case report N=1 |
AMY-101 intravenously 6-hour loading infusion of 5 mg/kg mg/Kg/day, followed by 13 maintenance doses as 24-h continuous infusions, for a 14-day treatment period | Rapid clinical improvement and reduction in inflammatory biomarkers |
| Peffault de La Tour48 | Severe COVID-19 | Case series N=8 |
Eculizumab 3 infusions of 900 to 1200 mg every 4 days | 6/8 survivors Survivors had rapid clinical improvement and reduction of serum levels of inflammatory biomarkers |
| Zelek 202068 | COVID-19 ARDS With high circulating levels of terminal complement factors |
Case series N=5 |
LFG316 single 1500-mg dose by intravenous infusion | 4/5 patients had sustained improvement in clinical state persisting beyond C5 blockade |
| Laurence 2020 | Severe COVID-19 With evidence for skin deposition of terminal complement factors |
Case series N=3 |
Marked decline in D-dimers and neutrophil counts 1 patient had full recovery 1 patient died, and the last one had partial recovery |
|
| Diurno 2020 | Severe COVID-19 | Case series N=4 |
Eculizumab 900 mg Up to 4 weekly infusions | Marked clinical improvement within the first 48 hours after the first administration of eculizumab |
| Annane 202049 | COVID-19 ARDS | Quasi randomized N=80 |
Eculizumab single infusions of 900 to 1200 mg were administered intravenously over 45 min on days 1 (within 7 days of confirmed pneumonia or ARDS), 8, 15, and 22 | Eculizumab improved day 15 survival 82.9% (95% CI: 70.4%‒95.3%) with eculizumab and 62.2% (48.1%‒76.4%) without eculizumab (Log rank test, P = 0.04) More rapid resolution of inflammation, coagulopathy and organs dysfunction Increased secondary bacterial infections |
| Vlaar 202072 | Severe COVID-19 | Open-label, randomized phase 2 trial | Vilobelimab, IFX-1, anti-C5a antibody (up to seven doses of 800 mg intravenously) plus best supportive care or best supportive care only | Mortality by 28 days were 13% (95% CI 0–31) for the IFX-1 group and 27% (4–49) for the control group (adjusted hazard ratio for death 0·65 [95% CI 0·10–4·14]) There was no difference in PaO2/FiO2 ratio overtime |