{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T17:04:12Z","timestamp":1789664652685,"version":"4.0.1"},"reference-count":29,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018956","name":"NIHR Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To characterize its dose\u2010response relationship, BI\u2009655064 (an anti\u2010CD40 monoclonal antibody) was tested as an add\u2010on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 121 patients were randomized (2:1:1:2) to receive placebo or BI 655064 120, 180, or 240 mg and received a weekly loading dose for 3\u2009weeks followed by dosing every 2\u2009weeks for the 120 and 180 mg groups, and 120 mg weekly for the 240 mg group. The primary endpoint was complete renal response (CRR) at week 52. Secondary endpoints included CRR at week 26.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A dose\u2010response relationship with CRR at week 52 was not shown (BI 655064 120 mg, 38.3%; 180 mg, 45.0%; 240 mg, 44.6%; placebo, 48.3%). At week 26, 28.6% (120 mg), 50.0% (180 mg), 35.0% (240 mg), and 37.5% (placebo) achieved CRR. The unexpected high placebo response prompted a post hoc analysis evaluating confirmed CRR (cCRR, at weeks 46 and 52). cCRR was achieved in 22.5% (120 mg), 44.3% (180 mg), 38.2% (240 mg), and 29.1% (placebo) of patients. Most patients reported \u22651 adverse event (BI 655064, 85.7\u201395.0%; placebo, 97.5%), most frequently infections and infestations (BI 655064 61.9\u201375.0%; placebo 60%). Compared with other groups, higher rates of serious (20% vs. 7.5\u201310%) and severe infections (10% vs. 4.8\u20135.0%) were reported with 240 mg BI 655064.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The trial failed to demonstrate a dose\u2010response relationship for the primary CRR endpoint. Post hoc analyses suggest a potential benefit of BI 655064 180 mg in patients with active LN.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.42557","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T13:41:48Z","timestamp":1684244508000},"page":"1983-1993","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Clinical and Biomarker Responses to <scp>BI<\/scp> 655064, an Antagonistic <scp>Anti\u2010CD40<\/scp> Antibody, in Patients With Active Lupus Nephritis: A Randomized, <scp>Double\u2010Blind<\/scp>, <scp>Placebo\u2010Controlled<\/scp>, Phase <scp>II<\/scp> Trial"],"prefix":"10.1002","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1712-0637","authenticated-orcid":false,"given":"David R.","family":"Jayne","sequence":"first","affiliation":[{"name":"Department of Medicine University of Cambridge  Cambridge 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