Safety, Tolerability, and Pharmacokinetics of Anti-SARS-CoV-2 Immunoglobulin Intravenous (Human) Investigational Product (COVID-HIGIV) in Healthy Adults: a Randomized, Controlled, Double-Blinded, Phase 1 Study.

Anti-SARS-CoV-2 immunoglobulin (human) investigational product (COVID-HIGIV) is a purified immunoglobulin preparation containing SARS-CoV-2 polyclonal antibodies. This single-center clinical trial aimed to characterize the safety and pharmacokinetics of COVID-HIGIV in healthy, adult volunteers. Participants were enrolled to receive one of three doses of COVID-HIGIV (100, 200, 400 mg/kg) or placebo in a 2:2:2:1 randomization scheme. Between 24 December 2020 and 27 July 2021, 28 participants met eligibility and were randomized with 27 of these 28 (96.4%) being administered either COVID-HIGIV (n = 23) or placebo (n = 4). Only one SAE was observed, and it occurred in the placebo group. A total of 18 out of 27 participants (66.7%) reported 50 adverse events (AEs) overall. All COVID-HIGIV-related adverse events were mild or moderate in severity and transient. The most frequent AEs (>5% of participants) reported in the safety population were headache (n = 6, 22.2%), chills (n = 3, 11.1%), increased bilirubin (n = 2, 7.4%), muscle spasms (n = 2, 7.4%), seasonal allergies (n = 2, 7.4%), pyrexia (n = 2, 7.4%), and oropharyngeal pain (n = 2, 7.4%). Using the SARS-CoV-2 binding IgG immunoassay (n = 22, specific for pharmacokinetics), the geometric means of Cmax (AU/mL) for the three COVID-HIGIV dose levels (low to high) were 7.69, 17.02, and 33.27 AU/mL; the average values of Tmax were 7.09, 7.93, and 5.36 h, respectively. The half-life of COVID-HIGIV per dose level was 24 d (583 h), 31 d (753 h), and 26 d (619 h) for the 100 mg/kg, 200 mg/kg, and 400 mg/kg groups, respectively. The safety and pharmacokinetics of COVID-HIGIV support its development as a single-dose regimen for postexposure prophylaxis or treatment of COVID-19.