A phase I clinical study of the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR-2106, an anti-CD40 antibody, following single intravenous or subcutaneous administration in healthy participants.

Authors

Jie Huang, Qiang-da Huang, Jin-Lian Xie, Qian Wu, Kun-Hong Deng, Shuang Yang, Xiao-Yan Yang, Ying Wang, Ying Zhu, Qiuna Du, Chuanpin Chen, Guo-Ping Yang

Published in

European journal of pharmacology. Pages 179291. Aug 26, 2026. Epub Aug 26, 2026.

Abstract

SHR-2106 is a humanized IgG1 monoclonal antibody that blocks CD40-CD40L interactions and has demonstrated immunosuppressive activity and graft-prolonging effects in preclinical studies. This first-in-human Phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single intravenous or subcutaneous doses of SHR-2106 in healthy adults.
This randomized, double-blind, placebo-controlled Phase I study enrolled healthy participants. Fifty-one participants were enrolled in seven cohorts and received five intravenous doses (50-1200 mg) or two subcutaneous doses (300 and 600 mg). Safety, serum pharmacokinetics, CD40 occupancy on B cells, and anti-drug antibodies were assessed using standard clinical and bioanalytical methods.
SHR-2106 demonstrated a favourable safety and tolerability profile, and most treatment-emergent adverse events were mild to moderate laboratory abnormalities with incidence rates comparable to placebo. SHR-2106 exhibited nonlinear pharmacokinetics consistent with target-mediated drug disposition, with a dose-dependent increase in geometric mean terminal half-life following intravenous administration (1.83-10.7 days). Absolute bioavailability after subcutaneous administration was approximately 60%. CD40 occupancy exceeded 80% within 24 hours at all doses, with saturation duration increasing from 7 to 70 days across the intravenous dose range and remaining comparable between routes at matched doses. Anti-drug antibody incidence decreased with increasing intravenous dose and did not significantly affect pharmacokinetics or pharmacodynamics.
SHR-2106 was well tolerated and achieved rapid and sustained CD40 engagement, supporting dose and route selection for Phase II studies.

PMID:
42648529
Bibliographic data and abstract were imported from PubMed on 27 Aug 2026.

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