David R. Jayne, Jürgen Steffgen, Juanita Romero-Diaz, Ingeborg Bajema, Dimitrios T. Boumpas, Kajohnsak Noppakun, Hirofumi Amano, Harold Michael Gomez, Bancha Satirapoj, Yingyos Avihingsanon, Ratana Chawanasuntorapoj, Magdalena Madero, Beata Naumnik, Rhona Recto, Nora Fagan, Ivette Revollo, Jing Wu, Sudha Visvanathan, Richard Furie
{"title":"活动性狼疮性肾炎患者对拮抗性抗CD40抗体BI 655064的临床和生物标志物反应：一项随机、双盲、安慰剂对照的II期试验。","authors":"David R. Jayne, Jürgen Steffgen, Juanita Romero-Diaz, Ingeborg Bajema, Dimitrios T. Boumpas, Kajohnsak Noppakun, Hirofumi Amano, Harold Michael Gomez, Bancha Satirapoj, Yingyos Avihingsanon, Ratana Chawanasuntorapoj, Magdalena Madero, Beata Naumnik, Rhona Recto, Nora Fagan, Ivette Revollo, Jing Wu, Sudha Visvanathan, Richard Furie","doi":"10.1002/art.42557","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>To characterize its dose-response relationship, BI 655064 (an anti-CD40 monoclonal antibody) was tested as an add-on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN).</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <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 weeks followed by dosing every 2 weeks 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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>A dose-response 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 ≥1 adverse event (BI 655064, 85.7–95.0%; placebo, 97.5%), most frequently infections and infestations (BI 655064 61.9–75.0%; placebo 60%). Compared with other groups, higher rates of serious (20% vs. 7.5–10%) and severe infections (10% vs. 4.8–5.0%) were reported with 240 mg BI 655064.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>The trial failed to demonstrate a dose-response relationship for the primary CRR endpoint. Post hoc analyses suggest a potential benefit of BI 655064 180 mg in patients with active LN.</p>\n </section>\n </div>","PeriodicalId":129,"journal":{"name":"Arthritis & Rheumatology","volume":"75 11","pages":"1983-1993"},"PeriodicalIF":11.4000,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clinical and Biomarker Responses to BI 655064, an Antagonistic Anti-CD40 Antibody, in Patients With Active Lupus Nephritis: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial\",\"authors\":\"David R. Jayne, Jürgen Steffgen, Juanita Romero-Diaz, Ingeborg Bajema, Dimitrios T. Boumpas, Kajohnsak Noppakun, Hirofumi Amano, Harold Michael Gomez, Bancha Satirapoj, Yingyos Avihingsanon, Ratana Chawanasuntorapoj, Magdalena Madero, Beata Naumnik, Rhona Recto, Nora Fagan, Ivette Revollo, Jing Wu, Sudha Visvanathan, Richard Furie\",\"doi\":\"10.1002/art.42557\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>To characterize its dose-response relationship, BI 655064 (an anti-CD40 monoclonal antibody) was tested as an add-on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <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 weeks followed by dosing every 2 weeks 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>A dose-response 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 ≥1 adverse event (BI 655064, 85.7–95.0%; placebo, 97.5%), most frequently infections and infestations (BI 655064 61.9–75.0%; placebo 60%). Compared with other groups, higher rates of serious (20% vs. 7.5–10%) and severe infections (10% vs. 4.8–5.0%) were reported with 240 mg BI 655064.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>The trial failed to demonstrate a dose-response relationship for the primary CRR endpoint. Post hoc analyses suggest a potential benefit of BI 655064 180 mg in patients with active LN.</p>\\n </section>\\n </div>\",\"PeriodicalId\":129,\"journal\":{\"name\":\"Arthritis & Rheumatology\",\"volume\":\"75 11\",\"pages\":\"1983-1993\"},\"PeriodicalIF\":11.4000,\"publicationDate\":\"2023-05-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Arthritis & Rheumatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/art.42557\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Arthritis & Rheumatology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/art.42557","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
Clinical and Biomarker Responses to BI 655064, an Antagonistic Anti-CD40 Antibody, in Patients With Active Lupus Nephritis: A Randomized, Double-Blind, Placebo-Controlled, Phase II Trial
Objective
To characterize its dose-response relationship, BI 655064 (an anti-CD40 monoclonal antibody) was tested as an add-on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN).
Methods
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 weeks followed by dosing every 2 weeks 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.
Results
A dose-response 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 ≥1 adverse event (BI 655064, 85.7–95.0%; placebo, 97.5%), most frequently infections and infestations (BI 655064 61.9–75.0%; placebo 60%). Compared with other groups, higher rates of serious (20% vs. 7.5–10%) and severe infections (10% vs. 4.8–5.0%) were reported with 240 mg BI 655064.
Conclusion
The trial failed to demonstrate a dose-response relationship for the primary CRR endpoint. Post hoc analyses suggest a potential benefit of BI 655064 180 mg in patients with active LN.
期刊介绍：
Arthritis & Rheumatology is the official journal of the American College of Rheumatology and focuses on the natural history, pathophysiology, treatment, and outcome of rheumatic diseases. It is a peer-reviewed publication that aims to provide the highest quality basic and clinical research in this field. The journal covers a wide range of investigative areas and also includes review articles, editorials, and educational material for researchers and clinicians. Being recognized as a leading research journal in rheumatology, Arthritis & Rheumatology serves the global community of rheumatology investigators and clinicians.
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