A Phase I, Randomized, Single-Dose Study to Evaluate the Biosimilarity of QL1206 to Denosumab Among Chinese Healthy Subjects
Hong Zhang, Min Wu, Xiaoxue Zhu, Cuiyun Li, Xiaojiao Li, Jixuan Sun, Chengjiao Liu, Quan Liu, Wei Wei, Junqi Niu, Yanhua Ding
Abstract
Objective: This study was conducted to explore the tolerance, variability, pharmacokinetics (PK) and pharmacodynamics (PD) of denosumab biosimilar (QL1206) in Chinese healthy subjects. Methods: This is a randomized, double-blind, two-arm, parallel study performed to examine the bioequivalence of denosumab biosimilar termed as QL1206 with that of Xgeva® (Denosumab) as a reference drug. A single dose of 120 mg/kg of the denosumab biosimilar or Xgeva® was administered to the subjects, who were followed up for 134 days. Results: Similar PK properties as those of Xgeva® were exhibited by QL1206. When compared to QL1206 with Xgeva®, the 90% confidence intervals of the ratios for Cmax, AUC0-t, and AUC0-∞ were observed to be within 80–125%. The intersubject variability (inter-CV) ranged from 29% to 39.5%. Six and three subjects in the QL1206 and Xgeva® groups were found to be positive for the ADA and negative for the Nab, respectively. The CTX1 concentration–time profiles appeared similar (about 80% decrease from 48 hours to134 days) between QL1206 and Xgeva® groups. Adverse events (AEs) were observed in 92.6% and 93.4% of subjects in the QL1206 and Xgeva® groups, respectively. Reduction in blood calcium level was found to be the most common AE recorded, with an incidence of 72.8% versus 72.4% in the QL1206 and Xgeva® groups, respectively. Conclusion: Similar PK and PD characteristics were exhibited by QL1206 as compared to those of Xgeva®. The inter-CV was slightly large. The safety profiles of denosumab biosimilars and Xgeva® were found to be similar.