The similarity of pharmacokinetics, pharmacodynamics, safety, and immunogenicity between recombinant fully human anti-RANKL monoclonal antibody injection (MW032) and denosumab (Xgeva®) in healthy Chinese subjects: A single-center, randomized, double-blind, single-dose, parallel-controlled clinical study

Abstract

ObjectiveTo compare the pharmacokinetics (PK), pharmacodynamics (PD), safety and immunogenicity between MW032 (denosumab biosimilar) and Xgeva® (denosumab) in healthy Chinese subjects. Study designIn this single-center, randomized, double-blind, single-dose, parallel-controlled design study, 120 healthy male subjects were randomized 1:1 to receive a single dose subcutaneous injection of 120 mg MW032 or Xgeva®, with an observation period of 161 days. The primary endpoint was the bioequivalence of PK parameters (Cmax, AUC0-t), and secondary endpoints including PD parameters, safety, and immunogenicity. ResultsOne hundred and twelve subjects completed the study, including 56 subjects in each group. The geometric mean ratio and 90% CI for AUC0−t and Cmax were 1.117 (1.034, 1.205) and 1.060 (0.984, 1.142), respectively, which were both within the equivalence interval (0.8, 1.25). The inter-subject variation ranged from 21.37% to 27.37%. The PD parameters between MW032 and Xgeva® were similar. There was no statistically significant difference in the positive incidence of anti-drug antibody test between the two groups. Both MW032 and Xgeva® appeared to be well-tolerated and no Grade 3 or above serious adverse reactions occurred. The adverse reactions observed in the study were reported for denosumab generally. Moreover, there were no high-incidence or previously unreported adverse reactions. ConclusionThis study evidenced that the PK profiles of MW032, a denosumab biosimilar, and Xgeva® were bioequivalent. We also found that the PDs, safety, and immunogenicity were similar between the two drugs. Therefore, our results supported the next confirmatory studies for the development of MW032.