Abstract
Introduction
NNC0109-0012, a novel human monoclonal antibody that binds to and neutralizes the activity of interleukin–20, was investigated as a potential treatment for inflammatory diseases. Pharmacokinetic (PK) modeling was performed using data from four completed clinical phase 1/2 trials to better understand the clinical PK of NNC0109-0012.
Methods
The populations included were patients with rheumatoid arthritis (RA), chronic plaque psoriasis, and healthy volunteers. NNC0109-0012 was administered subcutaneously at various dose levels (0.01–3 mg/kg) as single dose, once weekly, or multiple doses every second week for up to 12 doses. Noncompartmental methods were used to describe the PK parameters. Population PK was analyzed using nonlinear mixed-effects modeling, with body weight as the main covariate and gender, age, and population as additional covariates.
Results
Across studies (N = 116), mean age and body weight ranged from 38 to 58 years and 72 to 96 kg, respectively. NNC0109-0012 displays linear PK. Time to maximum plasma concentration occurred at approximately 1 week, and the terminal half-life was approximately 3 weeks. Clearance and volume of distribution increased proportionally to body weight. No difference in clearance or volume of distribution was observed between gender or different age groups; however, clearance was slightly lower in healthy volunteers than in patients with RA.
Conclusion
The PK profile of NNC0109-0012 is similar to other monoclonal antibodies directed against soluble targets.
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Acknowledgments
This study and the associated article processing charges were supported by Novo Nordisk A/S, Denmark. Under the direction of the authors, editorial assistance was provided by Jane Phillips, PhD, and Maryann Travaglini, PharmD, of Complete Healthcare Communications, Inc. (Chadds Ford, PA, USA), and was funded by Novo Nordisk A/S. The authors had full control of the data reported in this article. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.
Conflict of interest
Mia Sandberg Lundblad is an employee of Novo Nordisk and holds stock options in Novo Nordisk. Rune Viig Overgaard is an employee of Novo Nordisk and holds stock options in Novo Nordisk. Marie Göthberg is an employee of Novo Nordisk and holds stock options in Novo Nordisk. Marianne Scheel Fjording is an employee of Novo Nordisk and holds stock options in Novo Nordisk. Estelle Watson is an employee of Novo Nordisk and holds stock options in Novo Nordisk.
Compliance with ethics guidelines
The clinical trials described in this manuscript were approved by the national health authorities and the local ethics committee, as applicable, and were performed in accordance with the ethical standards in the 1964 Declaration of Helsinki and its later amendments. All clinical trial participants gave their informed consent before inclusion in the study.
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Lundblad, M.S., Overgaard, R.V., Göthberg, M. et al. Clinical Pharmacokinetics of the Anti-Interleukin-20 Monoclonal Antibody NNC0109-0012 in Healthy Volunteers and Patients with Psoriasis or Rheumatoid Arthritis. Adv Ther 32, 228–238 (2015). https://doi.org/10.1007/s12325-015-0191-7
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DOI: https://doi.org/10.1007/s12325-015-0191-7