ABSTRACT
Background: Reactivation of BK virus (BKV) infection can cause significant kidney disease in immunocompromised patients. BKV nephropathy is a leading cause of allograft loss in kidney transplant recipients. There are currently no effective or BKV-specific therapies. MAU868 is a novel monoclonal human IgG1 that binds to the BKV major capsid protein with potent in vitro neutralizing activity against the 4 major BKV genotypes. Method(s): This is a Phase 2, randomized, placebo-controlled, double-blind study in patients (pts) who received a kidney transplant within one year. Pts had BK viremia;either >=104 copies/ml within 10 days of randomization or >=103 copies/ml in 2 consecutive samples 1-3 wks apart with most recent value measured within 10 days of randomization. Pts were randomized (2:1) to MAU868 or placebo intravenously (IV) every 28 days for 12 wks, with 24 wks follow-up. This analysis reports efficacy results at 16 and 36 wks for 2 cohorts: Cohort 1: MAU868 1350 mg IV X4 doses, and Cohort 2: MAU868 6750 mg IV followed by 1350 mg IV X3 doses. The primary endpoint was safety;BKV viral load (VL) response to treatment was assessed as secondary endpoints and post-hoc analyses. Result(s): 20 pts received MAU868 and 8 pts received placebo;all completed 12 wks of treatment and 24 wks of follow-up. Baseline characteristics were comparable between groups. Median baseline VL was 16,700 log10 BKV DNA copies/ml (range 1,200-1,800,000). MAU868 was well tolerated, with a comparable frequency of adverse events and serious adverse events between groups through wk 36. There were 2 deaths in the MAU868 group due to COVID-19 infection deemed unrelated to study drug. The antiviral effect was greater in the MAU868 group than in the placebo group at wk 16 and sustained through wk 36 (Table). Conclusion(s): MAU868 was well tolerated and demonstrated clinically meaningful BK antiviral activity in kidney transplant recipients with BK viremia. These results support the further development of MAU868 as a therapy for BK viremia. (Table Presented).