Safety, pharmacokinetics and pharmacodynamics of SHR-1703, an innovative long-acting anti-interleukin-5 monoclonal antibody, in healthy subjects: a randomized, double-blind, dose-escalation, placebo-controlled phase I study

ABSTRACT

Objective

SHR-1703 is a novel humanized IgG1 monoclonal antibody with high IL-5 affinity and prolonged half-life, aiming to control eosinophil-related diseases. The study intended to evaluate pharmacokinetics, pharmacodynamics, immunogenicity, safety, and tolerability of SHR-1703 in healthy subjects.

Methods

A single-center, randomized, double-blind, placebo-controlled, single-dose escalation phase I study was conducted. 42 subjects were allocated to sequentially receive single subcutaneous injection of 20, 75, 150, 300, and 400 mg SHR-1703 or placebo.

Results

After administration, SHR-1703 was slowly absorbed with median T_max ranging from 8.5 to 24.5 days. Mean t_1/2 in 150 to 400 mg doses was 86 to 100 days. C_max and AUC increased in nearly dose-proportional pattern over range of 75 to 400 mg SHR-1703. After receiving SHR-1703, peripheral blood eosinophils (EOS) greatly decreased from baseline, which showed no significant change from baseline in placebo group. Magnitude and duration of reduction of EOS rose with increased dosing of SHR-1703. In 400 mg dose, remarkable efficacy of reducing EOS maintained up to approximately 6 months post single administration. Moreover, SHR-1703 exhibited low immunogenicity (2.9%), favorable safety, and tolerability in healthy subjects.

Conclusion

Pharmacokinetics, pharmacodynamics, immunogenicity, safety, and tolerability of SHR-1703 support further clinical development of SHR-1703 in eosinophil-associated diseases.

Clinical Trial registration

The study was registered on the ClinicalTrials.gov (identifier: NCT04480762).

KEYWORDS:

• SHR-1703
• Phase I study
• eosinophil-related diseases
• safety
• pharmacokinetics
• pharmacodynamics

Declaration of interest

Y Luo, M Fu and K Shen are employees of Jiangsu Hengrui Pharmaceuticals 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.

Authors’ contribution

L Yang: Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Data curation, Writing-original draft, Writing-review & editing, Visualization, Supervision, Project administration; Y Fang: Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Data curation, Writing-original draft, Writing-review & editing, Visualization, Supervision, Project administration; Y Luo: Methodology, Software, Formal analysis, Investigation, Data curation, Writing-review & editing, Visualization; M Fu: Methodology, Software, Formal analysis, Investigation, Data curation, Writing-review & editing, Visualization; K Shen: Methodology, Software, Formal analysis, Investigation, Data curation, Writing-review & editing, Visualization; Z Luo: Conceptualization, Methodology, Validation, Investigation, Resources, Writing-original draft, Writing-review & editing, Visualization, Supervision, Project administration, Funding acquisition. All authors have read and approved the final version of the manuscript.

Acknowledgments

We express our appreciation to all the study nurses in Phase I clinical trial center ward for sampling. We would like to acknowledge all the human subjects for participating in the study.

Data availability statement

The data in the study are available by contacting the corresponding author upon reasonable request for research purpose.

Additional information

Funding

The study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd. and grants from the Science and Technology Department of Sichuan Province, China (No. 23NSFSC3997).