Two-year treatment experience with BI 655064, an antagonistic anti-CD40 antibody, in patients with active lupus nephritis: An exploratory, phase II maintenance trial.

ObjectiveTo evaluate the long-term efficacy and safety of different doses of BI 655064 versus placebo added to standard of care during maintenance treatment for lupus nephritis (LN).Methods1293.13 was an exploratory, phase II maintenance trial. Patients were eligible for entry if they had completed 1 year of randomised treatment with BI 655064 (120, 180 or 240 mg) or placebo in the 1293.10 trial, responded to treatment at Year 1 (complete renal response [CRR], partial renal response or urinary protein/creatinine ratio ≤1) and consented to continue treatment. The primary endpoint was the proportion of patients with CRR without renal flares at Year 2. Secondary endpoints included change from baseline in Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores and safety/tolerability.Results69/121 patients (57.0%) from the 1293.10 trial entered 1293.13. The adjusted proportion of patients with CRR decreased in all groups between Year 1 (BI 655064: 53.4%-72.7%; placebo: 71.4%) and Year 2 (BI 655064: 48.2%-59.5%; placebo: 57.5%). At Year 2, mean decreases in total SELENA-SLEDAI scores were greatest with BI 655064 240 mg (-10.6 points), followed by 120 mg (-8.9 points), 180 mg (-7.2 points) and placebo (-5.3 points). SELENA-SLEDAI non-renal scores decreased at Year 1 (BI 655064: -3.0 to -3.4; placebo: -1.8); this pattern remained with BI 655064 during Year 2 (-2.4 to -4.1), whereas placebo returned to near-baseline scores (-0.4). Over 2 years of treatment, almost all patients (97.1%) experienced ≥1 adverse event (AE). Compared with the other groups, higher rates of serious AEs (42.9% vs 23.1%-33.3%)-mainly driven by serious infections (23.8% vs 7.7%-14.3%)-and severe AEs (47.6% vs 13.3%-28.6%) were reported with BI 655064 240 mg.ConclusionsThis exploratory, phase II maintenance trial failed to demonstrate the benefits of BI 655064 on renal outcomes in the treatment of LN. However, some benefits in total and non-renal SELENA-SLEDAI scores were observed.