Safety, tolerability, pharmacokinetics, and pharmacodynamics of SHR-2010, a novel anti-MASP-2 antibody, in healthy volunteers: a randomized, double-blind, placebo-controlled phase 1 study

Background This first-in-human study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of SHR-2010, a novel humanized IgG4 monoclonal antibody targeting mannan-binding lectin serine protease-2, in healthy adults.Research design and methods In this randomized, double-blind, phase 1 study, eligible participants were randomly assigned to single ascending doses of SHR-2010 or placebo (32 via intravenous drip: 6:2; 0.3, 1.5, 4.0, and 8.0 mg/kg; 29 via subcutaneous injection: 8:2; 4.0, 8.0, and 12.0 mg/kg). The primary endpoints were safety and tolerability.Results SHR-2010 was well tolerated. Treatment-related adverse events (TRAEs) were similar in SHR-2010 groups (55.3% [26/47]) and placebo groups (78.6% [11/14]). No deaths or severe TRAEs were reported. In the intravenous dose groups, the Cmax increased proportionally with the dose, while the AUC increased slightly more than the dose increment. In the subcutaneous injection groups, Cmax and AUC demonstrated a linear relationship with dose. SHR-2010 demonstrated a notable inhibitory effect on lectin pathway, with the mean maximum inhibition rates exceeding 80.0% across the tested doses, compared to 6.7% with placebo.Conclusions SHR-2010 was safe and well tolerated after a single dose and exhibited robust blockade of the lectin pathway, supporting further development.Trial registration The trial is registered at ClinicalTrials.gov (NCT05398510).