title: First-in-human study to assess guselkumab (anti-IL-23 mAb) pharmacokinetics/safety in healthy subjects and patients with moderate-to-severe psoriasis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Biologics Clinical Pharmacology, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA, 19477, USA.
authors: Yanli
authors: Y
authors: Zhuang
authors: Compound Development, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA, 19477, USA.
authors: Cesar
authors: C
authors: Calderon
authors: Compound Development, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA, 19477, USA.
authors: Stanley J
authors: SJ
authors: Marciniak
authors: Clinical Research, DePuy Orthopaedics US Inc., West Chester, PA, 19380, USA.
authors: Esther
authors: E
authors: Bouman-Thio
authors: Immunology, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA, 19477, USA.
authors: Philippe
authors: P
authors: Szapary
authors: Biologics Clinical Pharmacology, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA, 19477, USA.
authors: Tong-Yuan
authors: TY
authors: Yang
authors: Biologics Clinical Pharmacology, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA, 19477, USA.
authors: Allen
authors: A
authors: Schantz
authors: Biologics Clinical Pharmacology, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA, 19477, USA.
authors: Hugh M
authors: HM
authors: Davis
authors: Quantitative Sciences, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA, 19477, USA.
authors: Honghui
authors: H
authors: Zhou
authors: Biologics Clinical Pharmacology, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, PA, 19477, USA. zxu5@its.jnj.com.
authors: Zhenhua
authors: http://orcid.org/0000-0002-3415-0133
authors: Z
authors: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D019540:Area Under Curve; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D053759:Interleukin-23 / Q000037:antagonists & inhibitors / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003879:Dermatologic Agents; D053759:Interleukin-23; C000588857:guselkumab
keywords: Anti-interleukin-23; First-in-human; Guselkumab; Monoclonal antibody; Pharmacokinetics; Safety