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Pharmacokinetics and Pharmacodynamics of Novel Long-Acting Ropeginterferon Alfa-2b in Healthy Chinese Subjects

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Abstract

Introduction

Ropeginterferon alfa-2b is a novel mono-pegylated human recombinant interferon (IFN) with the addition of N-terminal proline covalently attached by a 40-kDa polyethylene (peg) moiety. The present study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD) profiles and safety of the product in healthy Chinese.

Methods

Forty subjects were enrolled and treated with a single subcutaneous injection of either 180 mcg peg-IFN alfa-2a or 90, 180, and 270 mcg ropeginterferon alfa-2b.

Results

The mean Tmax of ropeginterferon alfa-2b was 92–141 h and the elimination half-life was 78–129 h. Dose-related, non-proportional increase in ropeginterferon alfa-2b exposure was observed, which was higher than for peg-IFN alfa-2a. The PD parameters were similar between each dose level of ropeginterferon alfa-2b. The mean Tmax of β2-microglobulin ranged from 118 to 132 h after a single dose of ropeginterferon alfa-2b. The average Emax was 3 mcg/ml in all dose levels and the mean AUEC0–t ranged from 1608 to 1775 h/mcg/ml. The TEAEs were comparable among each treatment group and no death nor drug-related SAE was reported.

Conclusion

Ropeginterferon alfa-2b is safe and well tolerated after a single subcutaneous injection up to 270 mcg in healthy Chinese.

Clinical Trial Registration

www.chinadrugtrials.org.cn, CTR20190451.

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Acknowledgements

Funding

This study and the journal’s Rapid Service Fee was funded by PharmaEssentia Corp. The interpretation and conclusions in this study are based on the authors’ view.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Author Contributions

CLT proposed the concept for study and contributed to the design of the study. YWH acted as the medical monitor. YWH, CWT, WW, and JGZ participated in the design of the study, preparation of the protocol, CRF, review of data/analyses, internal and external presentation, as well as preparation of the CSR. YWH and CYT were major contributors in writing the manuscript. BS and MXW were investigators to conduct study and contributed to acquisition, analysis and interpretation of data. YWH, CYT, and AQ contributed to the interpretation of the results and reviewing the manuscript.

List of Investigators

Bo-Song and Mei-xia Wang were investigators in Beijing Youan Hospital, Capital Medical University, Beijing, China.

Disclosures

Chan-Yen Tsai, Chung-Wei Tsai, Albert Qin, and Chingleou Teng work for PharmaEssentia Corporation headquarter in Taipei, Taiwan. William Wang and Jingjing Zhang work for PharmaEssentia Biotech Ltd, Beijing, China. Yi-Wen Huang was the Senior Director of Medical Research and Head of Pharmacovigilance at PharmaEssentia Corporation headquarter in Taipei, Taiwan from July 02, 2018 to May 31, 2021. Yi-Wen Huang moved to Taipei Medical University Hospital. Bo-Song and Mei-xia Wang have nothing to disclose.

Compliance with Ethics Guidelines

The study was conducted in accordance with the provisions of the Declaration of Helsinki and its amendments, US Food and Drug Administration (FDA) guidance, and principles of Good Clinical Practice (GCP) from the International Conference on Harmonization (ICH) guidelines. The protocol and informed consent form were reviewed and approved by IRB of Beijing Youan Hospital, Capital Medical University (Protocol Number: A17-101) prior to the screening or enrollment of the study participant. The purpose of the study was explained to the subjects before they provided their written informed consent. Subjects were provided with copies of their signed informed consent forms. At the study center, the clinical staff was available to subjects before they entered the study and throughout their participation in the study to answer questions about the study. Subjects were informed about any new development of the product during the study that might have influenced their continued participation in the study.

Data Availability

The data that support the finding of this study are available on request to PharmaEssentia Corp.

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, No. 252, Wuxing Street, Xinyi District, Taipei City, 110301, Taiwan

    Yi-Wen Huang

  2. Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, No. 252, Wuxing Street, Xinyi District, Taipei City, 110301, Taiwan

    Yi-Wen Huang

  3. School of Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

    Yi-Wen Huang

  4. PharmaEssentia Corporation, Taipei, Taiwan

    Yi-Wen Huang, Chan-Yen Tsai, Chung-Wei Tsai, Albert Qin & Chingleou Teng

  5. PharmaEssentia Biotech Ltd, Beijing, China

    William Wang & Jingjing Zhang

  6. Beijing Youan Hospital, Capital Medical University, Beijing, China

    Bo Song & Mei-xia Wang

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  1. Yi-Wen Huang
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Corresponding author

Correspondence to Yi-Wen Huang.

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Huang, YW., Tsai, CY., Tsai, CW. et al. Pharmacokinetics and Pharmacodynamics of Novel Long-Acting Ropeginterferon Alfa-2b in Healthy Chinese Subjects. Adv Ther 38, 4756–4770 (2021). https://doi.org/10.1007/s12325-021-01863-y

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  • DOI: https://doi.org/10.1007/s12325-021-01863-y

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