Journal Article

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

Hou, Qiaoyun, Wu, Junzhen, Yan, Hongyue, Guo, Bujing, Qiu, Yanping, Yu, Shuyan, He, Jinjie, Zhang, Xiang, Zhang, Jing, Song, Han, Yang, Yifan, Zhao, Junxue, Xue, Yu, Chen, Bo

2025

Overview

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 Tmax was 2.00–3.00 days, mean Cmax was 4.75–87.40 μg/mL, mean AUC0‐t was 20.29–1262.50 day*μg/mL, mean Vz/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)

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Adolescent / ADP-ribosyl Cyclase 1 - antagonists & inhibitors / ADP-ribosyl Cyclase 1 - immunology / Adult / Adverse events / Antibodies, Monoclonal, Humanized - administration & dosage / Antibodies, Monoclonal, Humanized - adverse effects / Antibodies, Monoclonal, Humanized - immunology / Antibodies, Monoclonal, Humanized - pharmacokinetics / anti‐CD38 mAbs / Apoptosis / Autoimmune diseases / Bioavailability / CD38 antigen / CM313 / Dose-Response Relationship, Drug / Double-Blind Method / Drug dosages / Enrollments / Female / Healthy Volunteers / Humans / Immunogenicity / Immunoglobulin A / Immunoglobulin G / Immunoglobulin M / Infusions, Intravenous / Injections, Subcutaneous / Lupus / Lymphocytes / Lymphocytes B / Lymphocytes T / Male / Middle Aged / Monoclonal antibodies / Monocytes / Multiple myeloma / Pharmacodynamics / Pharmacokinetics / Phase 1 / Placebos / Plasma / safety / Thrombocytopenia / Young Adult