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A first-in-human study to assess the safety and pharmacokinetics of monoclonal antibodies against human cytomegalovirus in healthy volunteers

Dole, Kiran and Segal, Florencia and Feire, Adam and Magnusson, Baldur and Rondon, Juan C and Vemula, Janardhana Rao and Yu, Jing and Pang, Yinuo and Pertel, Peter (2016) A first-in-human study to assess the safety and pharmacokinetics of monoclonal antibodies against human cytomegalovirus in healthy volunteers. Antimicrobial Agents and Chemotherapy, 60 (5). pp. 2881-2887. ISSN 0066-4804; 1098-6596

Abstract

Human cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients and treatment options are limited by toxicities. CSJ148 is a combination of two anti-HCMV human monoclonal antibodies (LJP538 and LJP539) that bind to and inhibit the function of viral HCMV glycoprotein B (gB) and the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. Here, we evaluated the safety, tolerability, and pharmacokinetics of a single intravenous dose of LJP538 or LJP539 or their combination in healthy volunteers. Adverse events and laboratory abnormalities occurred sporadically with similar incidence between antibody and placebo groups and without any apparent relationship to dose. No subject who received antibody developed a hypersensitivity, infusion-related reaction or anti-drug antibodies. After intravenous administration, both LJP538 and LJP539 demonstrated typical human IgG1 pharmacokinetic properties, with slow clearances, limited volumes of distribution, and long terminal half-lives. The pharmacokinetic parameters were linear and dose proportional for both antibodies across the 50-fold range of doses evaluated in the study. There was no apparent impact on pharmacokinetics when the antibodies were administered alone or in combination. CSJ148 and the individual monoclonal antibodies were safe and well tolerated, with pharmacokinetics as expected for human immunoglobulin.

Item Type: Article
Additional Information: Unmapped bibliographic data: LA - English [Field not mapped to EPrints] ST - A first-in-human study to assess the safety and pharmacokinetics of monoclonal antibodies against human cytomegalovirus in healthy volunteers [Field not mapped to EPrints] AU - Dole, K. [Field not mapped to EPrints] AU - Segal, F. P. [Field not mapped to EPrints] AU - Feire, A. [Field not mapped to EPrints] AU - Magnusson, B. [Field not mapped to EPrints] AU - Rondon, J. C. [Field not mapped to EPrints] AU - Vemula, J. [Field not mapped to EPrints] AU - Yu, J. [Field not mapped to EPrints] AU - Pang, Y. [Field not mapped to EPrints] AU - Pertel, P. [Field not mapped to EPrints] AD - (Dole, Segal, Feire, Yu, Pang, Pertel) Novartis Institutes for BioMedical Research, Cambridge, MA, United States [Field not mapped to EPrints] DB - Embase [Field not mapped to EPrints] DP - Ovid Technologies [Field not mapped to EPrints] AN - 20160348185 [Field not mapped to EPrints]
Keywords: Cytomegalovirus
Date Deposited: 29 Nov 2016 00:45
Last Modified: 29 Nov 2016 00:45
URI: https://oak.novartis.com/id/eprint/26684

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