title: 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.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
authors.forename: Kiran
authors.initials: K
authors.lastname: Dole
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA florencia.segal@novartis.com.
authors.forename: Florencia Pereyra
authors.initials: FP
authors.lastname: Segal
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA Novartis Institutes for BioMedical Research, Emeryville, California, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Feire
authors.affiliation: Novartis Pharmaceuticals AG, Basel, Switzerland.
authors.forename: Baldur
authors.initials: B
authors.lastname: Magnusson
authors.affiliation: Elite Research Institute, Miami, Florida, USA.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Rondon
authors.affiliation: Novartis Pharmaceuticals, Hyderabad, India.
authors.forename: Janardhana
authors.initials: J
authors.lastname: Vemula
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
authors.forename: Yinuo
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Pertel
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D003587:Cytomegalovirus / Q000187:drug effects* / Q000472:pathogenicity*; D004311:Double-Blind Method; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000998:Antiviral Agents; D007074:Immunoglobulin G