Pharmacokinetics, pharmacodynamics, safety and immunogenicity of recombinant, fully human anti-RANKL monoclonal antibody (MW031) versus denosumab in Chinese healthy subjects: a single-center, randomized, double-blind, single-dose, parallel-controlled trial

ABSTRACT

Background

MW031 is a biosimilar candidate of denosumab (Prolia®). This study aimed to compare the pharmacokinetics, pharmacodynamics, safety and immunogenicity of MW031 to denosumab in healthy Chinese participants.

Research design and methods

In this single-center, randomized, double-blind, parallel-controlled, single-dose trial, participants were given 60 mg MW031 (N = 58) or denosumab (N = 61) by subcutaneous injection and observed for 140 days. The primary endpoint was the bioequivalence of PK parameters (C_max, AUC_0-∞), and secondary endpoints including PD parameter, safety, and immunogenicity.

Results

A comparison of main PK parameters showed that the geometric mean ratios (GMR) (90% confidence intervals [CIs]) of AUC_0-∞ and C_max for MW031 over denosumab were 105.48% (98.96%, 112.43%) and 98.58% (92.78%, 104.75%), respectively. The inter-CV values of AUC_0-∞ and C_max for MW031 ranged from 19.9% to 23.1%. PD parameter (sCTX) in the MW031 and denosumab groups were similar, and the positivity rates of immunogenicity were 0% in both groups. This study also showed similar safety profiles in both groups, and there were no drug-related, high-incidence and previously unreported adverse reactions.

Conclusion

This trial confirmed similar pharmacokinetic profiles of MW031 and denosumab in healthy male participants, and pharmacodynamic profile, immunogenicity and safety were comparable for both drugs.

Trial registration

NCT04798313; CTR20201149

KEYWORDS:

• Denosumab
• MW031
• pharmacokinetics
• pharmacodynamics
• safety
• equivalence

Abbreviations

Table

Declaration of interest

Y Guo, W Xu, Z Hu, Y Xiao and H Yu are employees of Mabwell (Shanghai) Bioscience Co., Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Ethics

The protocol, amendments and other ethics committee review documents of this trial were assessed and approved by the Ethics Committee of Drug for Clinical Trials, Peking University (PKU) Care, Luzhong Hospital, Zibo. The trial was conducted according to the Declaration of Helsinki, the Good Clinical Practice for Drugs (GCP) issued by the National Medical Products Administration and other regulations[11]. All participants provided signed informed consent before study enrollment.

Author contributions

Study design, investigation and manuscript drafting: Y Guo and J Hou. Investigation: W Xu, Z Hu, Y Di, T Guo. Manuscript revision: Y Xiao and H Yu. Approval of the final manuscript: all authors.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14712598.2023.2178298

Additional information

Funding

This paper was funded by Mabwell (Shanghai) Bioscience Co., Ltd.