Pharmacokinetics, Safety, and Tolerability of NPC‐21, an Anti‐Cytomegalovirus Monoclonal Antibody, in Healthy Japanese and White Adult Men: A Randomized, Placebo‐Controlled, First‐in‐Human Phase 1 Study

Abstract

NPC-21 (EV2038) is a fully human monoclonal antibody that targets the antigenic domain 1 of glycoprotein B on the human cytomegalovirus (hCMV) envelope. NPC-21 has been shown to have broadly neutralizing activity and to inhibit cell-to-cell transmission of hCMV in preclinical studies. It is currently in development for the prophylactic or preemptive treatment of hCMV in patients receiving a solid-organ transplant or hematopoietic stem cell transplant. A first-in-human phase 1 study was conducted to assess the pharmacokinetics, safety, and tolerability of NPC-21 in healthy adult men. Forty participants (Japanese, n = 32; White, n = 8) were randomly assigned to receive a single intravenous dose of NPC-21 1, 3, 10, or 20 mg/kg or placebo. Six Japanese participants were included in each dose group and six White participants received a 10-mg/kg dose. The placebo group included 8 Japanese participants and 2 White participants. All 40 participants completed the study. Serum concentration, maximum serum concentration, area under the plasma concentration-time curve from time 0 to the last measurable concentration, and area under the plasma concentrationtime curve from time 0 to infinity increased dose dependently; dose proportionality was linear. NPC-21 demonstrated a biphasic elimination pattern, with an estimated half-life between 612 and 790 hours. NPC-21 was safe and well tolerated up to 20 mg/kg. All adverse events were mild, and none led to treatment discontinuation or were considered related to the study drug. There were no differences in pharmacokinetics or safety between Japanese and White participants. These results support further investigation of NPC-21.

A fully human neutralizing monoclonal antibody targeting a highly conserved epitope of the human cytomegalovirus glycoprotein B

“…Regarding the IC 90 values of cell-to-cell spread ( Fig 1C ), in vivo findings suggest that at least one 10 mg/kg dose of EV2038 every 28 days may be sufficient to prevent further HCMV infection. The half-life of EV2038 was estimated to be around 12 days in cynomolgus monkeys, extending up to 33 days in healthy adults, according to a phase I trial [ 60 ]. The long half-life of circulating EV2038 contributes to a reduction in the dose, and consequently, the cost of antibody therapy.…”