Phase 2, Randomized, Double-blind, Placebo-controlled Study of Fiztasovimab (NPC-21) for Kidney Transplant Recipients at High Risk of Cytomegalovirus Infection (LionHeart21).

Background: Kidney transplantation (KT) has dramatically improved the quality of life of patients with end-stage kidney disease. However, the incidence of opportunistic infections has also increased because of immunosuppression. A common infection after KT is cytomegalovirus (CMV). In KT recipients, we assessed the efficacy and safety of fiztasovimab (NPC-21), an anti-CMV monoclonal antibody.

Methods: This was a multicenter, randomized, double-blind, placebo-controlled, phase 2 study of NPC-21 for KT recipients with CMV donor-positive (D+)/recipient-negative (R-) serostatus. Patients were randomly assigned to receive monthly 6 or 12 mg/kg NPC-21, or placebo, in a 4:1:4 ratio. The primary efficacy endpoint was CMV infection by week 16.

Results: Eighty-seven KT recipients were randomized; 38, 11, and 38 received 6 mg/kg of NPC-21, 12 mg/kg of NPC-21, or placebo, respectively. CMV infections occurred in 29 of 38 (76.3%), 9 of 11 (81.8%), and 26 of 38 (68.4%) patients in the 6 mg/kg NPC-21, 12 mg/kg NPC-21, and placebo groups, respectively, with no statistically significant differences. CMV disease occurred in 2 of 49 (4.1%) versus 5 of 38 (13.2%) patients in the 6 and 12 mg/kg combined NPC-21 group versus the placebo group. The absolute difference (95% confidence interval) was -9.1 (-23.9 to 2.8). No significant adverse events were observed after NPC-21 administration.

Conclusions: NPC-21 was safe, but no significant efficacy difference was found between NPC-21 and placebo. Severe CMV infection was less likely in the NPC-21 group versus the placebo group. Further studies are needed to elucidate the role of NPC-21 in the prevention of CMV.