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Introduction: Adintrevimab is a fully human immunoglobulin G1 extended half-life monoclonal antibody that was developed to have broad neutralization against SARS-CoV, SARS-CoV-2, and other SARS-like CoVs with pandemic potential. Here we report the safety, pharmacokinetics (PK), serum viral neutralizing antibody (sVNA) titers, and immunogenicity results of the first three cohorts evaluated in the first-in-human study of adintrevimab in healthy adults. Methods: This is a phase 1, randomized, placebo-controlled, single ascending-dose study of adintrevimab administered intramuscularly (IM) or intravenously (IV) to healthy adults aged ≥ 18–55 years with no current or prior SARS-CoV-2 infection. Participants were randomized 8:2 to adintrevimab or placebo in each of three dose cohorts: adintrevimab 300 mg IM (cohort 1), 500 mg IV (cohort 2), and 600 mg IM (cohort 3). Follow-up was 12 months. Blood samples were taken predose and at multiple time points postdose up to month 12 to assess sVNA, PK, and antidrug antibodies (ADAs). Results: Thirty participants received a single dose of adintrevimab (n = 24; 8 per cohort) or placebo (n = 6). All except one adintrevimab participant in cohort 1 completed the study. No participants in any treatment arm experienced a study drug-related adverse event. Across adintrevimab-treated participants, 11 (45.8%) experienced at least one TEAE. All but one TEAE were mild in severity, and all were either viral infection or respiratory symptoms. There were no serious adverse events, discontinuations due to adverse events, or deaths. Adintrevimab exhibited a linear and dose-proportional PK profile and extended serum half-life (mean 96, 89, and 100 days in cohorts 1, 2, and 3, respectively). Participants receiving adintrevimab demonstrated dose-dependent increased sVNA titers and breadth across multiple variants. Conclusion: Adintrevimab at doses of 300 mg IM, 500 mg IV, and 600 mg IM was well tolerated in healthy adults. Adintrevimab demonstrated dose-proportional exposure, rapid development of neutralizing antibody titers, and an extended half-life. [ABSTRACT FROM AUTHOR]