LP-001, a Novel Long-Acting EPO-Fc Fusion Protein: A Phase I Dose-Escalation Study of Pharmacokinetics, Safety, and Tolerability in Healthy Chinese Subjects.

The objective of this study is to evaluate the safety, pharmacokinetics, and pharmacodynamics of LP-001 injection in healthy Chinese subjects. This was a single-center, double-blind, randomized, dose-escalation study. Fifty-six healthy adults were enrolled and randomly assigned to receive LP-001 or matched placebo. A total of 156.0 drug related adverse events occurred during treatment in 38 subjects who received LP-001 injection. The main events were grade 1 serum iron reduction and elevated triglycerides, which were considered related to the drug's erythropoietic effect and reversible. Pharmacokinetic exposure increased with dose (0.5-50 mcg·kg-1), but the increase in maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) was greater than the dose ratio (non-linear). Pharmacodynamics showed dose-dependent increases in hemoglobin (Hb), red blood cell count (RBC), hematocrit (HCT), and reticulocyte count (Rtc). The pharmacodynamic indicators in the 15 and 30 mcg·kg-1 multiple-dose groups were significantly higher than those in the placebo group, and the increase in RBC count was more pronounced in the 30 mcg·kg-1 group. LP001, a long-acting rhEPO, was safe and well-tolerated at all doses in this Phase I study. These findings support its continued development as a treatment for myelodysplastic syndromes (MDS).