Pharmacokinetics, Pharmacodynamics, and Immunogenicity of CM313 in Healthy Participants: An Open-Label/Double-Blind, Randomized, Placebo-Controlled Phase 1 Trial

Abstract

CM313, a novel humanized anti-CD38 monoclonal antibody, has demonstrated therapeutic potential in autoimmune diseases. This Phase 1 trial evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy participants following single ascending doses of CM313. Fifty-one participants received CM313 or placebo by SC injection at doses of 150 mg (1:1), 300 mg (2:1), and 600 mg (2:1), or by IV infusion at 8 mg/kg (2:1). All completed the trial. Treatment-emergent adverse events occurred in 90.9% of CM313-treated participants and 83.3% of placebo-treated participants, all mild or moderate. No serious adverse events were reported. SC injections of CM313 demonstrated a notably lower incidence of infusion-related reactions (600 mg SC: 20%) than IV infusion (8 mg/kg IV: 60%). CM313 exhibited nonlinear pharmacokinetics. Following a single SC dose, the median T_max was 2.00–3.00 days, mean C_max was 4.75–87.40 μg/mL, mean AUC_0-t was 20.29–1262.50 day*μg/mL, mean V_z/F was 2.63–21.20 L, mean clearance was 0.50–7.90 L/day, and mean half-life was 1.85–3.90 days. The bioavailability of the 600 mg SC dose was 66% of the 8 mg/kg IV dose. CM313 induced rapid and sustained reductions in total IgA, IgE, IgG, and IgM levels by 40%–80% from baseline. Both SC and IV formulations demonstrated potent CD38 binding activity and markedly depleted NK cells by ≥ 90% within 2 days. CM313 also achieved 80%–90% CD38 receptor occupancy on B cells, T cells, and monocytes within 1 week. Overall, single doses of CM313 demonstrated favorable safety, tolerability, PK, and PD in healthy participants.

Trial Registration: ClinicalTrials.gov (NCT06285227)