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 add-on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN).

METHODS: 121 patients were randomized (2:1:1:2) to placebo or BI 655064 120mg, 180mg or 240mg and received a weekly loading dose for 3 weeks followed by dosing every 2 weeks for the 120mg and 180mg groups, and 120mg weekly for the 240mg group.

PRIMARY ENDPOINT: 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 120mg, 38.3%; 180mg, 45.0%; 240mg, 44.6%; placebo, 48.3%). At Week 26, 28.6% (120mg), 50.0% (180mg), 35.0% (240mg), 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% (120mg), 44.3% (180mg), 38.2% (240mg), 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 240mg 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 180mg in patients with active LN. This article is protected by copyright. All rights reserved.