A phase 1, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of sipavibart in healthy Japanese adults.

BACKGROUND: Sipavibart, a recombinant human immunoglobulin G1-based monoclonal antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, is approved in Japan for prevention of COVID-19 in immunocompromised individuals. This phase 1 study evaluated the safety and pharmacokinetics (PK) of sipavibart in Japanese individuals. METHODS: Healthy Japanese adults (18-55 years) were enrolled into one of three cohorts, and randomized to sipavibart 300 mg intramuscularly (IM) or placebo (Cohort 1), sipavibart 600 mg IM or placebo (Cohort 2), or sipavibart 1200 mg intravenously (IV) or placebo (Cohort 3). Participants were followed for approximately 1 year post-administration. Safety/tolerability (occurrence of adverse events [AEs]), PK, pharmacodynamics (PD; neutralizing response against SARS-CoV-2 variants), and immunogenicity (development of anti-drug antibodies [ADAs]) were assessed. RESULTS: Twenty-four individuals (56% male) were randomized, with eight participants (sipavibart, n = 6; placebo, n = 2) in each cohort. Through Day 91 (primary safety endpoint), AEs were reported in five participants (27.8%) in the total sipavibart group and one (16.7%) in the pooled placebo group. There were no deaths, serious or treatment-related AEs, or AEs leading to discontinuation. PK parameters indicated consistent exposure across sipavibart administration routes and doses. Neutralizing antibody titers against all tested SARS-CoV-2 variants increased over time. A linear PK/PD relationship was observed across serum sipavibart concentrations for the SARS-CoV-2 variants tested. No participants developed treatment-emergent ADAs. CONCLUSIONS: Single IM and IV doses of sipavibart were well tolerated in healthy Japanese adults, with a linear PK/PD relationship across tested SARS-CoV-2 variants.