Pharmacokinetic Characteristics, Safety, and Tolerability of Telitacicept, an Injectable Recombinant Human B-Lymphocyte Stimulating Factor Receptor-Antibody Fusion Protein, in Healthy Chinese Subjects

Abstract

Telitacicept, an injectable recombinant human B-lymphocyte stimulating factor receptor-antibody fusion protein, is a new dual B lymphocyte stimulator (BLyS)/APRIL (a proliferation-inducing ligand) inhibitor that effectively blocks proliferation of B lymphocytes. This study evaluates the pharmacokinetic characteristics, tolerability, and safety of a single subcutaneous injection of various doses (80, 160, and 240 mg) of telitacicept in healthy Chinese subjects. This trial is a single-center, randomized, open-label phase I clinical study that includes three dose groups (80, 160, and 240 mg) with 12 subjects in each dose group. The subjects were randomly assigned to different dose groups in a 1:1:1 ratio for a single subcutaneous administration trial. After a single dose, the maximum serum concentration (C_max ) of total and free telitacicept was reached within 0.5-1 days. The elimination half-lives of total and free telitacicept at doses of 80-240 mg were 10.9-11.9 days and 11-12.5 days, respectively. The formation and elimination of the BLyS-telitacicept complex were much slower; the median time to C_max was 15-57 days and was significantly prolonged with increasing dose. Only two of the 36 healthy subjects had positive antidrug antibodies with antibody titers of 1:15. The severity of adverse events was mild or moderate, and no higher treatment-emergent adverse events were reported. In conclusion, total telitacicept within a dose range of 80-240 mg and free telitacicept within a dose range of 160-240 mg had linear pharmacokinetic characteristics.

Keywords: BLyS/APRIL; pharmacokinetics; safety; telitacicept; tolerability.

Figure 1

The mean serum concentration of total telitacicept. The error bars are SD.

Figure 2

The mean serum concentration of free telitacicept. The error bars are SD.

Figure 3

The mean serum concentration of the B lymphocyte stimulator‐telitacicept complex. The error bars are SD.

Figure 4

Analysis of the rate of change (%) in the levels of immunological indicators (IgG, IgA, IgM, C3, C4, and B cells) from baseline after medication. Rate of change (%) = (postdose value − baseline value)/baseline value × 100%.