학술논문
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.
Document Type
Academic Journal
Author
Jayne DR; Department of Medicine, University of Cambridge, Cambridge, UK.; Steffgen J; Boehringer Ingelheim International GmbH, Biberach, Germany.; Romero-Diaz J; Instituto Nacional de Ciencias Médicas y Nutrición 'Salvador Zubiran', Mexico City, Mexico.; Bajema I; Department of Pathology and Medical Biology, University of Groningen, University Medical Center, Groningen, the Netherlands.; Boumpas DT; Department of Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Noppakun K; Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.; Amano H; Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.; Gomez HM; Angeles University Foundation Medical Center, Angeles City, Philippines.; Satirapoj B; Division of Nephrology, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.; Avihingsanon Y; Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.; Chawanasuntorapoj R; Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.; Madero M; National Institute of Cardiology Ignacio Chávez, Mexico City, Mexico.; Naumnik B; Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Bialystok, Poland.; Recto R; Mary Mediatrix Medical Center, Lipa City, Philippines.; Fagan N; Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut.; Revollo I; Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany.; Wu J; Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut.; Visvanathan S; Boehringer Ingelheim Pharmaceuticals Inc, Ridgefield, Connecticut.; Furie R; Northwell Health and Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York.
Source
Publisher: Wiley Country of Publication: United States NLM ID: 101623795 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2326-5205 (Electronic) Linking ISSN: 23265191 NLM ISO Abbreviation: Arthritis Rheumatol Subsets: MEDLINE
Subject
Language
English
Abstract
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.
(© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
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.
(© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)