In:
Clinical Pharmacology & Therapeutics, Wiley, Vol. 105, No. 4 ( 2019-04), p. 1031-1039
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 ( AE s), few moderate AE s, and a low incidence of infection‐related AE s similar to placebo treatment. The tolerability and consistency of M281 pharmacokinetics and pharmacodynamics support further evaluation of M281 in diseases mediated by pathogenic IgG.
Type of Medium:
Online Resource
ISSN:
0009-9236
,
1532-6535
DOI:
10.1002/cpt.2019.105.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2040184-X
SSG:
15,3
Permalink