A First-In-Human Phase 1 Study of SHR-1906, a Humanized Monoclonal Antibody Against Connective Tissue Growth Factor, in Healthy Participants.

New therapeutic targets and drugs are urgently needed to halt the fibrosing process in idiopathic pulmonary fibrosis (IPF). SHR-1906 is a novel fully humanized monoclonal antibody against the connective tissue growth factor (CTGF) which plays an essential role in the genesis of IPF. We assessed the safety, tolerability, pharmacokinetics, and immunogenicity of single dose SHR-1906 in healthy participants. This was a randomized, double-blind, placebo-controlled, dose-escalation, phase 1 study. Twelve healthy participants for each dose level were enrolled to receive single ascending doses of SHR-1906 intravenously (1.5, 6, 12, 20, 30, and 45 mg/kg) or placebo and followed for 71 days. The primary endpoints were safety and tolerability. Treatment-related treatment-emergent adverse events (TEAEs) occurred in 25 participants (46.3%) in the SHR-1906 group and 11 (61.1%) in the placebo group. No serious adverse events occurred. Over the dose range investigated, the geometric mean clearance was 0.14 - 0.63 mL/h/kg, the geometric mean volume of distribution at steady state was 47.4 - 75.5 mL/kg, and the t 1/2 was 51.9 - 349 h. SHR-1906 showed nonlinear pharmacokinetics. The peak concentration increased in a dose-proportional manner, while the area under the concentration-time curve (AUC) showed a greater than dose-proportional increase. Anti-drug antibodies (ADAs) of SHR-1906 were detected in nine of 54 participants (16.7%). A single dose of SHR-1906 up to 45 mg/kg demonstrated a favorable tolerability profile in healthy participants. The pharmacokinetics and immunogenicity of SHR-1906 were evaluated, supporting further clinical development.