Phase I Evaluation of the Safety and Pharmacokinetics of a Single-Dose Intravenous Injection of a Murine Monoclonal Antibody against Hantaan Virus in Healthy Volunteers

Abstract

Anti-Hantaan virus monoclonal antibody (AHM) is a murine monoclonal antibody against Hantaan virusbeing developed for the treatment of hemorrhagic fever with renal syndrome. The purpose of the present study was to describe the tolerance and pharmacokinetics of an intravenously administered single ascending dose of AHM in Chinese healthy volunteers. Four cohorts of 22 healthy subjects received AHM at 2.5 to 20 mg, and the results indicated that AHM was well tolerated. We established a highly sensitive, rapid, and accurate immunoassay for the kinetic analysis of AHM in serum. Serial blood samples were obtained after intravenous administration for up to 17 days. A one-compartment model was determined to best describe the disposition of AHM. The maximal level in serum and the area under the serum concentration-time curve were proportional to the doses. The mean clearance, the half-life, and the volume of distribution were constant, irrespective of the dose. AHM was slowly cleared and had a half-life of approximately 110 h. These data support the use of a treatment regimen in which AHM is given only once intravenously.

Pharmacokinetics and Biodistribution Study of 7A7 Anti-Mouse Epidermal Growth Factor Receptor Monoclonal Antibody and Its Fragment in an Immunocompetent Mouse Model

“…This allows us to circumvent the main drawbacks of the use of radioactivity methods. Pharmacokinetics analyses using similar approaches involving an ELISA system with blood fractions and specific ligands have been reported and validated by other authors [33–35]. This analysis gave a t 1/2   β for 7A7 mAb of 23.9 h, very similar to the value of t 1/2   β obtained using the radioactivity method.…”

Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture

“…MAbs against HTNV have been developed. In China, a single-dose intravenous injection of a murine MAb against HTNV was developed and applied in healthy volunteers (Xu et al, 2009 ; Hall et al, 2010 ). It has been demonstrated that the anti-HTNV MAbs have anti-HTNV activity both in vitro and in vivo (Xu et al, 2002 ).…”

Human Antibody Neutralizes Severe Fever with Thrombocytopenia Syndrome Virus, an Emerging Hemorrhagic Fever Virus

“…Antibody has played a critical role in the treatment of a wide variety of viral diseases, such as those caused by Hantaan virus, cytomegalovirus, rabies virus, and respiratory syncytial virus infection (11)(12)(13)(14). The mechanisms of antibody protection include neutralization, complement activation, antibody-dependent cellular cytotoxicity, and opsonization (15).…”