A Randomized, Double-Blind, Placebo-Controlled Phase Ib Clinical Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Continuous Intravenous Infusion of STC3141 Injection in adult ARDS Patients

Increased circulating histones correlate with acute respiratory distress syndrome (ARDS) severity and prognosis. A histone-neutralizing polyanion molecule (STC3141) therapy in the rat acute lung injury (ALI) study showed benefits. We aimed to investigate the safety, tolerability, and pharmacokinetics of STC3141 in ARDS patients.A total of 16 ARDS patients were divided into three groups:a control group (N=4) and two treatment groups using two different doses of STC3141: 58·3mg/hr (N=6) and 87·5mg/hr (N=6). Each patient received a continuous intravenous infusion of either STC3141 or an equivalent volume of saline as a placebo for 72 hours and was followed up for 28 days. A total of 14 patients (87·5%) reported treatment-emergent adverse events (TEAEs): 5 in each STC3141 group (83·3%) and 4 in the placebo group (100%). STC3141-related TEAEs were reported by 3 patients (18·8%). None of the AEs led to treatment discontinuation or stopping the trial. While mortality rates were comparable, STC3141, especially at 58·3 mg/hr, may improve ventilator-free days and recovery speed. Pharmacokinetic analysis demonstrated dose-dependent increases in exposure parameters (Cmax and AUC) with less than proportional dose escalation, stable elimination characteristics (CL and Vss), and absence of nonlinear pharmacokinetics, though notable inter-individual variability was observed across both dose groups.STC3141 administration appeared to have an acceptable degree of safety and tolerability and expected pharmacokinetics in ARDS patients. Cautiously designed, larger randomized efficacy trials in ARDS are necessary to clarify the efficacy.