{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["78(6)"],"submitter":["Visvanathan S"],"funding":["Boehringer Ingelheim"],"pubmed_abstract":["<h4>Objective</h4>To evaluate the safety, efficacy and therapeutic mechanism of BI 655064, an antagonistic anti-CD40 monoclonal antibody, in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR).<h4>Methods</h4>In total, 67 patients were randomised to receive weekly subcutaneous doses of 120 mg BI 655064 (n=44) or placebo (n=23) for 12 weeks. The primary endpoint was the proportion of patients who achieved 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Safety was assessed in patients who received at least one dose of study drug.<h4>Results</h4>At week 12, the primary endpoint was not met, with 68.2% of patients treated with BI 655064 achieving an ACR20 vs 45.5% with placebo (p=0.064); using Bayesian analysis, the posterior probability of seeing a difference greater than 35% was 42.9%. BI 655064 was associated with greater changes in CD40-CD40L pathway-related markers, including reductions in inflammatory and bone resorption markers (interleukin-6, matrix metalloproteinase-3, receptor activator of nuclear factor-κB ligand), concentration of autoantibodies (immunoglobulin [Ig]G rheumatoid factor [RF], IgM RF, IgA RF) and CD95+ activated B-cell subsets. No serious adverse events (AEs) related to BI 655064 treatment or thromboembolic events occurred; reported AEs were mainly of mild intensity.<h4>Conclusion</h4>Although blockade of the CD40-CD40L pathway with BI 655064 in MTX-IR patients with RA resulted in marked changes in clinical and biological parameters, including reductions in activated B-cells, autoantibody production and inflammatory and bone resorption markers, with a favourable safety profile, clinical efficacy was not demonstrated in this small phase IIa study.<h4>Trial registration number</h4>NCT01751776."],"journal":["Annals of the rheumatic diseases"],"pagination":["754-760"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6579552"],"repository":["biostudies-literature"],"pubmed_title":["Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study."],"pmcid":["PMC6579552"],"pubmed_authors":["Rosenstock B","Vinisko R","Kellner H","Dokoupilova E","Padula SJ","Schwabe C","Baum P","Kwiatkowska B","Visvanathan S","Fine JS","Alten R","Petrikova A","Joseph D","Ptaszynski R","Muller-Ladner U","Ramanujam M","Steffgen J","Daniluk S","Eleftheraki AG"],"additional_accession":[]},"is_claimable":false,"name":"Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study.","description":"<h4>Objective</h4>To evaluate the safety, efficacy and therapeutic mechanism of BI 655064, an antagonistic anti-CD40 monoclonal antibody, in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR).<h4>Methods</h4>In total, 67 patients were randomised to receive weekly subcutaneous doses of 120 mg BI 655064 (n=44) or placebo (n=23) for 12 weeks. The primary endpoint was the proportion of patients who achieved 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Safety was assessed in patients who received at least one dose of study drug.<h4>Results</h4>At week 12, the primary endpoint was not met, with 68.2% of patients treated with BI 655064 achieving an ACR20 vs 45.5% with placebo (p=0.064); using Bayesian analysis, the posterior probability of seeing a difference greater than 35% was 42.9%. BI 655064 was associated with greater changes in CD40-CD40L pathway-related markers, including reductions in inflammatory and bone resorption markers (interleukin-6, matrix metalloproteinase-3, receptor activator of nuclear factor-κB ligand), concentration of autoantibodies (immunoglobulin [Ig]G rheumatoid factor [RF], IgM RF, IgA RF) and CD95+ activated B-cell subsets. No serious adverse events (AEs) related to BI 655064 treatment or thromboembolic events occurred; reported AEs were mainly of mild intensity.<h4>Conclusion</h4>Although blockade of the CD40-CD40L pathway with BI 655064 in MTX-IR patients with RA resulted in marked changes in clinical and biological parameters, including reductions in activated B-cells, autoantibody production and inflammatory and bone resorption markers, with a favourable safety profile, clinical efficacy was not demonstrated in this small phase IIa study.<h4>Trial registration number</h4>NCT01751776.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jun","modification":"2026-06-17T06:15:11.436Z","creation":"2026-06-17T03:07:59.221Z"},"accession":"S-EPMC6579552","cross_references":{"pubmed":["30902820"],"doi":["10.1136/annrheumdis-2018-214729"]}}