D14-02 Anti-c5a Antibody Stsa-1002 for Patients With Acute Respiratory Failure Due to Viral Pneumonia

Abstract Background Effective treatments for acute respiratory failure due to respiratory viral infection remain limited. C5a plays a critical role in the pathogenesis of viral infection. We aimed to evaluate whether the C5a antibody STSA-1002 could improve clinical outcomes in patients with acute respiratory failure due to respiratory viral infection. Methods We conducted a phase 1b/2, multi-center, double-blind, placebo-controlled trial. Participants aged between 18 and 85 years, suffering from acute respiratory failure due to respiratory viral infection, which was confirmed by microbiological examination with PaO2/FiO2 ≤ 200mmHg, were included. Patients were randomly assigned (1:1:1) to receive either STSA-1002 1350mg, STSA-1002 750mg or placebo. The STSA-1002 or matched placebo was administered to participants on days 1, 3 and 7, with an optional additional dose on day 14±1 at the physician's discretion. The primary endpoint was time to clinical improvement (TTCI), defined as either SpO2/FiO2 235 or PaO2/FiO2 200 mmHg, maintained for at least 48 hours, whichever occurred first, within 28 days. This trial is registered with ClinicalTrials.gov, NCT02949011. Findings Between December 9, 2023 and March 20, 2025, 49 patients were enrolled and randomized. Of the 47 patients who received study medication, 17 received STSA-1002 1350mg, 15 received STSA-1002 750mg, and 15 received placebo. The TTCI was 6.0 days in the STSA 1002 1350 mg group, 8.4 days in the STSA 1002 750 mg group and 7.4 days in the control group, with the subdistribution hazard ratio of 1.55 (95% CI, 0.68-3.55) for the STSA-1002 1350mg group and 1.04 (95% CI, 0.46-2.38) for STSA-1002 750mg group according to a competing risk model, both compared with the control group. Besides, the 28-day all-cause mortality was 5.88% (1/17) , 26.67% (4/15) and 40% (6/15) in the STSA-1002 1350mg, 750mg and control group, with between-group differences of -34.1% (95% CI, -61.3% to -6.9%) for the 1350mg group versus control and -13.3% (95% CI, -46.7% to 20.1%) for the 750mg group versus control. STSA-1002 was well tolerated. Interpretation The C5a antibody STSA-1002 demonstrated shorter TTCI and lower mortality in patients with acute respiratory failure due to respiratory viral infection, with evidence of a dose-response relationship. The STSA-1002 was well tolerated. These preliminary results support further evaluation of STSA-1002 in a phase 3 trial. This abstract is funded by: Beijing Municipal Health Commission's Outstanding Research Program and Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences