title: A phase 1, randomized study to assess the pharmacokinetic comparability of siltuximab derived from two different cell lines in healthy subjects.
abstract: Siltuximab, a monoclonal antibody (mAb) against interleukin (IL-6), is under development by Janssen Research & Development, LLC. During early clinical development, siltuximab was produced in a murine Sp2/0 myeloma cell line. The production cell line was switched to stably transfected Chinese hamster ovary (CHO) cell line for subsequent clinical development. A two-part, parallel-group, phase 1 study was designed to evaluate the safety and pharmacokinetics (PK) of a single IV administration of Sp2/0- and CHO-derived siltuximab in healthy subjects. The results from this study demonstrated PK comparability of siltuximab produced from Sp2/0 and CHO cell lines. The 90% confidence interval of the ratios of geometric means of Cmax and AUC0-84day following 1.4 mg/kg doses was (99.4%, 111.3%) and (98.1%, 109.6%), respectively, both within the pre-specified comparability range of 80-125%. Siltuximab derived from either the Sp2/0 or CHO cell lines was in general well tolerated and was not found to be immunogenic in this study.
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Xu
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Chao
authors.initials: C
authors.lastname: Han
authors.affiliation: Janssen Research & Development, LLC, Radnor, PA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Marini
authors.affiliation: Janssen Research & Development, LLC, Radnor, PA, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Ford
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Marciniak
authors.affiliation: Janssen Research & Development, LLC, Malvern, PA, USA.
authors.forename: Manny
authors.initials: M
authors.lastname: Lopez
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Bart
authors.initials: B
authors.lastname: Frederick
authors.affiliation: Janssen Biologics Europe, Leiden, The Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: de Vries
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Bandekar
authors.affiliation: Janssen Research & Development, LLC, Radnor, PA, USA.
authors.forename: Hugh M
authors.initials: HM
authors.lastname: Davis
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Honghui
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Janssen Research & Development, LLC, Spring House, PA, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Puchalski
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000096:biosynthesis / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016466:CHO Cells; D045744:Cell Line, Tumor; D003412:Cricetulus; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008875:Middle Aged; D008954:Models, Biological; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C504234:siltuximab
keywords: bioequivalence; biologics; manufacturing change; pharmacokinetics; siltuximab