A Randomized Phase 2 Study of MAU868 vs. Placebo to Treat BK Viremia in Kidney Transplant Recipients

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 (21) 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).