A phase 1, randomized study to assess the pharmacokinetic comparability of siltuximab derived from two different cell lines in healthy subjects

• Published in: Clinical pharmacology in drug development Vol. 3; no. 4; pp. 328 - 334
• Main Authors: Xu, Chao, Han, Chao, Marini, Joseph, Ford, Joyce, Marciniak, Stanley, Lopez Jr, Manny, Frederick, Bart, de Vries, Dick, Bandekar, Rajesh, Davis, Hugh M., Zhou, Honghui, Puchalski, Thomas A.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.07.2014; Wiley Subscription Services, Inc
• Subjects: Adult; Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - biosynthesis; Antibodies, Monoclonal - pharmacokinetics; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Area Under Curve; bioequivalence; biologics; Cell Line, Tumor; CHO Cells; Confidence intervals; Cricetulus; Cross-Over Studies; Double-Blind Method; Female; Flocculation; Half-Life; Humans; Infusions, Intravenous; Male; manufacturing change; Metabolic Clearance Rate; Mice; Middle Aged; Models, Biological; pharmacokinetics; Rodents; siltuximab; Therapeutic Equivalency; Young Adult; pharmacokinetics; siltuximab; biologics; bioequivalence; manufacturing change
• ISSN: 2160-763X; 2160-7648
• DOI: 10.1002/cpdd.86

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.