Safety, tolerability, pharmacokinetics, and immunogenicity of a human monoclonal antibody TQC2731 targeting thymic stromal lymphopoietin (TSLP) in healthy Chinese adults.

<bold>Background:</bold> TQC2731 is a fully human monoclonal antibody that targets TSLP, which has been found to be involved in Th2 and non-Th2 inflammation. TQC2731 is now been investigated in patients with asthma. <bold>Objectives:</bold> To evaluate the safety, tolerability, pharmacokinetics and immunogenicity of TQC2731 in healthy Chinese adults. <bold>Methods:</bold> In this phase I randomized, double-blind, placebo-controlled study, single subcutaneous (SC) doses of TQC2731 or placebo were administered to 44 healthy adults (12 to 630 mg). Single intravenous (IV) doses of TQC2731 210mg or placebo were administered to 10 healthy adults (8:2). Ten adults were randomized to receive TQC2731 420mg or placebo every 28 days for three doses. Safety, tolerability, immunogenicity and pharmacokinetic profiles were analyzed. <bold>Results:</bold> No deaths, treatment-related serious adverse events, or study discontinuations due to adverse events were reported. All the adverse events (AE) reported were of grade 1 or 2 expect 4 subjects experienced a grade 3 or 4 AE (2 subjects with increased creatine kinase, 1 subject with increased triglyceride, 1 subject with acute suppurative tonsillitis). Treatment emergent adverse events occurred at similar rates after TQC2731 and placebo treatment. TQC2731 displayed linear pharmacokinetics in healthy adults. Mean T_1/2 for both IV and SC administration of TQC2731 ranged from 17.2 to 26.1days. <bold>Conclusions:</bold> TQC2731 was well tolerated at all doses administered during the study in healthy Chinese adults. Our results support further clinical development of TQC2731 for asthma and other related diseases mediated by Th2 inflammation.