Safety, tolerability, pharmacokinetics and pharmacodynamics of an anti- oncostatin M monoclonal antibody in rheumatoid arthritis: results from phase II randomized, placebo-controlled trials

• DOI: 10.1186/ar4312
• Publication Date: 2013-09-24T07:45:00Z
• Authors: Ernest H Choy; Marina Bendit; Dana McAleer; Feng Liu; Maria Feeney; Sara Brett; Stefano Zamuner; Andrea Campanile; John Toso
• Keywords: Tolerability; Pharmacodynamics

Oncostatin M (OSM) has been implicated in the pathophysiology of rheumatoid arthritis (RA) through its effect on inflammation and joint damage. GSK315234 is a humanised anti-OSM Immunoglobulin G1 (IgG1) monoclonal antibody (mAb). This 3-part study examines safety, tolerability efficacy patients with active RA.This was (Parts A, B C), multicenter study. Part A were randomised, double-blind, placebo-controlled, Bayesian adaptive dose finding studies to investigate tolerability, efficacy, pharmacokinetics pharmacodynamics single (Part A) 3 repeat B) intravenous infusions RA background methotrexate (MTX). C dose, single-blind, placebo-controlled assess subcutaneously administered MTX.The primary endpoint mean change DAS28 at Day 28 56 C. All receiving least one included safety analysis. In there statistically significant differences between mg/kg placebo 56, 84 91. There also difference 0.3 mg/kg, 10 as compared placebo, 84. Although these changes small occurred late, they supported progression determine therapeutic potential GSK315234. For B, no observed 6 placebo. C, 40, 100 500 mg subcutaneous group, No findings any time points for EULAR response criteria, ACR20, ACR50 or ACR70. An exploratory analysis clinical, pharmacokinetic data suggests lack may be due moderate binding affinity rapid off-rate higher OSM receptor causing protein carrier prolonging half life accumulation OSM/antibody complex serum synovial fluid.Our highlighted importance mAb fully neutralize target how this influence potentially worsen disease activity. Using an high should test hypothesis examine RA.ClinicalTrials.gov no: NCT00674635.