Anti-C5a Antibody STSA-1002 for Patients With ARDS Due to Viral Pneumonia: A Phase 1b/2, Multicenter, Randomized, Double-Anonymized, Placebo-Controlled Trial

Background: ARDS constitutes a major cause of mortality, with limited therapeutic options. Research Question: Is STSA-1002, an anti-C5a monoclonal antibody, safe and clinically beneficial in ARDS caused by viral pneumonia? Study Design and Methods: This was a phase 1b/2, multicenter, double-anonymizzed, placebo-controlled trial. Participants aged between 18 and 85 years with ARDS caused by viral pneumonia and PaO2/FIO2 ≤ 200 mm Hg were included. Patients were randomly assigned (1:1:1) to receive STSA-1002 1,350 mg, STSA-1002 750 mg, 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 end point was time to clinical improvement. Clinical improvement was defined as either blood oxygen saturation/FIO2 > 235 mm Hg or PaO2/FIO2 > 200 mm Hg, maintained for at least 48 hours, whichever occurred first, within 28 days. Results: Between December 9, 2023, and March 20, 2025, a total of 49 patients were enrolled and randomized to treatment. Among the 47 patients who received study medication, 17 received STSA-1002 1,350 mg, 15 received STSA-1002 750 mg, and 15 received placebo. The time to clinical improvement was 6.0 days in the STSA 1002 1,350 mg group, 8.4 days in the STSA 1002 750 mg group, and 7.4 days in the control group. A subdistribution hazard ratio of 1.55 (95% CI, 0.68-3.55) was reported for the STSA-1002 1,350 mg group and 1.04 (95% CI, 0.46-2.38) for the STSA-1002 750 mg group according to a competing risk model, both compared with the control group. Following adjustment for baseline PaO2/FIO2, the subdistribution hazard ratio was 1.22 (95% CI, 0.52-2.86) and 1.13 (95% CI, 0.47-2.75), respectively. The 28-day all-cause mortality was 5.88% (1 of 17), 26.67% (4 of 15), and 40% (6 of 15). STSA-1002 was well tolerated. Interpretation: STSA-1002 exhibited a favorable safety profile and potential efficacy. These findings warrant confirmation in a phase 3 trial. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT06038916; URL: www.clinicaltrials.gov © 2026 The Author(s)