Safety, Pharmacokinetics, and Pharmacodynamics of TQ-A3334, an Oral Toll-Like Receptor 7 Agonist, in Healthy Individuals.

Zhang, Hong; Hu, Yue; Wu, Min; Liu, Jingrui; Li, Xiaojiao; Zhu, Xiaoxue; Li, Cuiyun; Chen, Hong; Liu, Chengjiao; Niu, Junqi; Ding, Yanhua

BACKGROUND & AIMS TQ-A3334, a selective, oral toll-like receptor (TLR)-7 agonist, is being developed to treat chronic hepatitis B (CHB). This study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of TQ-A3334 in healthy participants. RESEARCH DESIGN AND METHODS The effects of a single-ascending dose of TQ-A3334 (0.2-1.8 mg) combined with food (1.2 mg) were evaluated in 48 healthy participants. RESULTS No serious adverse events or discontinuations occurred in the study. The most common adverse reactions were lymphocyte count decreased and headache, which were generally consistent with IFN-α exposure and the mechanism of action of a TLR7 agonist. TQ-A3334 was rapidly absorbed, with a time to maximum plasma concentration of 0.42-0.5 h. Systemic exposure (Cmax and AUC) to TQ-A3334 increased with a slight saturation proportion to dose. Food reduced the exposure of TQ-A3334. The concentrations of MCP-1, ISG-15, MX-1, and OAS-1 were observed to be slightly dose-dependent, ranging from 1.0 to 1.8 mg TQ-A3334. CONCLUSIONS Oral doses of 0.2-1.8 mg appeared to be safe and tolerated. PD activity was seen at doses ranging from 1.0 to 1.8 mg, indicating its possible future use to treat CHB.