M281, an Anti-FcRn Antibody: Pharmacodynamics, Pharmacokinetics, and Safety Across the Full Range of IgG Reduction in a First-in-Human Study.
Clin Pharmacol Ther
; 105(4): 1031-1039, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30402880
ABSTRACT
M281 is a fully human, anti-neonatal Fc receptor (FcRn) antibody that inhibits FcRn-mediated immunoglobulin G (IgG) recycling to decrease pathogenic IgG while preserving IgG production. A randomized, double-blind, placebo-controlled, first-in-human study with 50 normal healthy volunteers was designed to probe safety and the physiological maximum for reduction of IgG. Intravenous infusion of single ascending doses up to 60 mg/kg induced dose-dependent serum IgG reductions, which were similar across all IgG subclasses. Multiple weekly doses of 15 or 30 mg/kg achieved mean IgG reductions of ≈85% from baseline and maintained IgG reductions ≥75% from baseline for up to 24 days. M281 was well tolerated, with no serious or severe adverse events (AEs), few moderate AEs, and a low incidence of infection-related AEs similar to placebo treatment. The tolerability and consistency of M281 pharmacokinetics and pharmacodynamics support further evaluation of M281 in diseases mediated by pathogenic IgG.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina G
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Receptores Fc
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Antígenos de Histocompatibilidade Classe I
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Anticorpos
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA