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Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Stapokibart in Healthy Volunteers and Adult Subjects with Atopic Dermatitis

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Abstract

Introduction

Stapokibart, a novel humanized anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits the signaling of IL-4 and IL-13, which are key drivers of type 2 inflammation in atopic dermatitis (AD). This study aimed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of stapokibart in a randomized, double-blind, placebo-controlled single ascending dose (SAD) study and a multiple ascending dose (MAD) study.

Methods

The SAD study enrolled 33 healthy male adults aged 18–65 years at a single center. The MAD study enrolled 39 patients with moderate-to-severe AD aged 18–70 years at seven centers. Enrolled subjects were randomized to subcutaneous (SC) doses of stapokibart (75–600 mg) or placebo. Serum thymus and activation-regulated chemokine (TARC) and total immunoglobulin E (IgE) were measured as PD biomarkers for stapokibart.

Results

Similar PK characteristics were observed in healthy volunteers and subjects with AD after the initial administration. Stapokibart exhibited non-linear pharmacokinetics in both types of subjects. Following single doses, the mean maximum serum concentration (Cmax) ranged from 5.3 to 63.0 μg/mL, median Tmax ranged from 3.0 to 7.0 days, mean terminal half-life (t1/2z) ranged from 2.39 to 7.43 days, and mean apparent volume (Vz/F) ranged from 3.64 to 6.73 L in healthy subjects. The mean AUC accumulation ratio was 2.29 in subjects with AD after three doses of stapokibart 300 mg administered every 2 weeks. The median serum total IgE and TARC levels on day 43 decreased from baseline by 14.9–25.2% and 48.6–77.0%, respectively, among subjects with AD receiving three doses of stapokibart. No subjects developed grade ≥ 3 adverse events (AEs) or serious AEs or discontinued the study because of AEs. The incidence of AEs was similar between stapokibart and placebo groups.

Conclusion

Stapokibart showed favorable pharmacokinetics, pharmacodynamics, safety, and tolerability in the SAD and MAD studies. Based on these results, phase II and phase III trials of stapokibart have been performed in subjects with moderate-to-severe AD.

Trial Registration

ClinicalTrials.gov Identifier NCT06161090 (29 November, 2023), NCT04893941 (15 May, 2021).

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Data Availability

The datasets generated and/or analyzed during the current studies are available from the corresponding author on reasonable request.

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Acknowledgements

We thank the participants of the study.

Funding

The studies and Rapid Service Fee were funded by KeyMed Biosciences (Chengdu) Co., Ltd.

Author information

Author notes

  1. Libo Zhang and Weilong Zhang contributed equally to this work.

Authors and Affiliations

  1. Keymed Biosciences (Chengdu) Co., Ltd, Chengdu, 610219, Sichuan, China

    Libo Zhang, Weilong Zhang, Yufeng Xu, Yingmin Jia, Zhichuan Li & Bo Chen

  2. United-Power Pharma Tech Co., Ltd., Bei**g, 102206, China

    Lihou Dong & Yunjuan Sun

  3. Phase I Trial Center, Peking University (PKU) Care, Luzhong Hospital, Zibo, 255400, Shandong, China

    Jie Hou

  4. Department of Dermatology, Peking University People’s Hospital, Bei**g, 100044, China

    Jianzhong Zhang

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  1. Libo Zhang
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Contributions

Libo Zhang and Weilong Zhang had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Libo Zhang, Zhichuan Li, Bo Chen, Jie Hou, Jianzhong Zhang. Acquisition, analysis, or interpretation of data: all authors. Drafting of the manuscript: Zhichuan Li, Libo Zhang, Weilong Zhang. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: Libo Zhang. Obtained funding: Bo Chen. Administrative, technical, or material support: Zhichuan Li, Bo Chen, Jie Hou, Jianzhong Zhang. Supervision: Zhichuan Li, Bo Chen, Jie Hou, Jianzhong Zhang.

Corresponding authors

Correspondence to Jie Hou or Jianzhong Zhang.

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Conflict of Interest

Libo Zhang, Weilong Zhang, Yufeng Xu, Yingmin Jia, and Zhichuan Li are employees of Keymed Biosciences (Chengdu) Co.,Ltd. Bo Chen is a shareholder of Keymed Biosciences (Chengdu) Co.,Ltd. All other authors declare no competing interests.

Ethical Approval

The study protocols and amendments for both trials were reviewed and approved by the ethics committees at each clinical trial site. Both studies were conducted in accordance with the Good Clinical Practice (GCP) guidelines and the principles of the Declaration of Helsinki. All subjects signed written informed consent prior to their participation in the studies.

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Zhang, L., Zhang, W., Xu, Y. et al. Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Stapokibart in Healthy Volunteers and Adult Subjects with Atopic Dermatitis. Adv Ther (2024). https://doi.org/10.1007/s12325-024-02887-w

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