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

doi:10.3389/fphar.2020.01329

A Phase I, Randomized, Single-Dose Study to Evaluate the Biosimilarity of QL1206 to Denosumab Among Chinese Healthy Subjects

Front Pharmacol. 2020 Oct 8:11:01329. doi: 10.3389/fphar.2020.01329. eCollection 2020.

Authors

Hong Zhang¹, Min Wu¹, Xiaoxue Zhu¹, Cuiyun Li¹, Xiaojiao Li¹, Jixuan Sun¹, Chengjiao Liu¹, Quan Liu², Wei Wei³, Junqi Niu⁴, Yanhua Ding¹

Affiliations

¹ Phase I Clinical Research Center, The First Hospital of Jilin University, Jilin, China.
² Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.
³ Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, China.
⁴ Department of Hepatology, The First Hospital of Jilin University, Changchun, China.

Abstract

Objective: This study was conducted to explore the tolerance, variability, pharmacokinetics (PK), and pharmacodynamics (PD) of denosumab biosimilar (QL1206) in healthy Chinese subjects.

Methods: This is a randomized, double-blind, two-arm, parallel study performed to examine the bioequivalence of denosumab biosimilar, 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 C_max, AUC_0-t, and AUC_0-∞ were observed to be within 80-125%. The inter-subject 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 the 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.

Keywords: biosimilar; denosumab; immunogenicity; inter-subject variability; pharmacodynamics; pharmacokinetics.