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First-in-human study to assess guselkumab (anti-IL-23 mAb) pharmacokinetics/safety in healthy subjects and patients with moderate-to-severe psoriasis

  • Clinical Trial
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Abstract

Purpose

The purpose of this study is to evaluate the pharmacokinetics, immunogenicity, safety, and tolerability of guselkumab, a human monoclonal antibody with high affinity and specificity for binding to interleukin-23.

Methods

In this first-in-human, phase 1, randomized study, a single intravenous (IV; 0.03–10 mg/kg) or subcutaneous (SC; 10–300 mg) dose of guselkumab was administered to 47 healthy subjects, and a single SC dose (placebo, 10, 30, 100, 300 mg) was administered to 24 patients with moderate-to-severe psoriasis.

Results

Mean maximum observed serum concentration and area under the zero-to-infinity serum concentration-time curve of guselkumab increased in an approximately dose-proportional manner over the dose range of 0.03–10 mg/kg following a single IV administration or 10–300 mg following a single SC administration. Mean clearance and volume of distribution ranged from 3.62–6.03 mL/day/kg and 99.38–123.22 mL/kg, respectively. Mean half-life ranged from 12 to 19 days in healthy subjects and patients with psoriasis. Among guselkumab-treated subjects/patients, 1/30 (3.3 %) healthy subjects in the IV group, 0/6 healthy subjects in the SC group, and 1/20 (5.0 %) patients with psoriasis tested positive for antibodies to guselkumab. No clinically significant adverse events were identified in this study.

Conclusion

Guselkumab pharmacokinetic profiles were generally comparable between healthy subjects and patients with psoriasis. Guselkumab, administered as an IV infusion or SC injection, was well tolerated in healthy subjects and patients with psoriasis.

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Acknowledgments

The authors thank the principal/coordinating investigators, Eleanor A. Lisbon MD MPH of Quintiles Phase One Services (Overland Park, KS, USA) for part 1 and Robert Matheson MD of Oregon Medical Research Center, P.C. (Portland, OR, USA) for part 2, who provided fully compensated services in the conduct of this trial, as well as the following institutional review boards at participating sites for their review and approval of the protocol and informed consent documents: Quintiles Phase One Services, Overland Park, KS, for part 1; Comprehensive Phase One, Miramar, FL; Rockefeller University, New York, NY; Central Dermatology, P.C., St. Louis, MO; Oregon Medical Research Center, P.C., Portland, OR; Therapeutics Clinical Research, San Diego, CA; Dermatology Research Associates, Los Angeles, CA; and Parexel International, Baltimore, MD for part 2. We also thank Michelle L. Perate, MS and Julie Thomas, PharmD of Janssen Scientific Affairs, LLC, for manuscript preparation and submission support.

Author contribution statement

All authors have met the ICMJE criteria for authorship by contributing to the study conception/design and/or data acquisition/analysis/interpretation, drafting/revising the manuscript, providing final approval for submission, and agreeing to be accountable for all aspects of the work.

Author information

Authors and Affiliations

  1. Biologics Clinical Pharmacology, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA, 19477, USA

    Yanli Zhuang, Tong-Yuan Yang, Allen Schantz, Hugh M. Davis & Zhenhua Xu

  2. Compound Development, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA, 19477, USA

    Cesar Calderon & Stanley J Marciniak Jr

  3. Clinical Research, DePuy Orthopaedics US Inc., West Chester, PA, 19380, USA

    Esther Bouman-Thio

  4. Immunology, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA, 19477, USA

    Philippe Szapary

  5. Quantitative Sciences, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA, 19477, USA

    Honghui Zhou

Authors
  1. Yanli Zhuang
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  2. Cesar Calderon
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  3. Stanley J Marciniak Jr
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  8. Hugh M. Davis
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  9. Honghui Zhou
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  10. Zhenhua Xu
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Corresponding author

Correspondence to Zhenhua Xu.

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Disclosures

Janssen Research & Development, LLC provided funding for this study. Authors Zhuang, Calderon, Marciniak, Szapary, Yang, Schantz, Davis, Zhou, and Xu are employees of Janssen Research & Development, LLC, and author Bouman-Thio is an employee of DePuy Orthopaedics US Inc., with both companies being wholly owned subsidiaries of Johnson & Johnson, Inc. All authors own the stock in Johnson & Johnson.

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Zhuang, Y., Calderon, C., Marciniak, S.J. et al. First-in-human study to assess guselkumab (anti-IL-23 mAb) pharmacokinetics/safety in healthy subjects and patients with moderate-to-severe psoriasis. Eur J Clin Pharmacol 72, 1303–1310 (2016). https://doi.org/10.1007/s00228-016-2110-5

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  • DOI: https://doi.org/10.1007/s00228-016-2110-5

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