A First-in-Human Study To Assess the Safety and Pharmacokinetics of Monoclonal Antibodies against Human Cytomegalovirus in Healthy Volunteers.

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.

• Authors: Kiran Dole, Florencia Pereyra Segal, Adam Feire, Baldur Magnusson, Juan C Rondon, Janardhana Vemula, Jing Yu, Yinuo Pang, Peter Pertel
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 60 Issue 5 Pg. 2881-7 (05 2016) ISSN: 1098-6596 [Electronic] United States
• PMID: 26926639 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Viral
• Antiviral Agents
• Immunoglobulin G

Topics

• Adult
• Antibodies, Monoclonal (pharmacokinetics, pharmacology, therapeutic use)
• Antibodies, Viral (immunology)
• Antiviral Agents (pharmacokinetics, pharmacology, therapeutic use)
• Cytomegalovirus (drug effects, pathogenicity)
• Double-Blind Method
• Female
• Healthy Volunteers
• Humans
• Immunoglobulin G (metabolism)
• Male
• Middle Aged
• Young Adult