A randomized placebo-controlled phase 1 safety and tolerability study of a novel human anti-MERS coronavirus polyclonal intravenous immunoglobulin produced from transchromosomic cattle

BACKGROUND: Passive immunotherapy approaches are being developed to prevent and treat a variety of human medical conditions. Here we report the first use of a fully-human polyclonal IgG immunoglobulin (SAB-301) produced from hyperimmune plasma of transchromosomic (Tc) cattle immunized with a Middle East Respiratory Syndrome (MERS) coronavirus vaccine. METHODS: We conducted a double-blind, placebo-controlled, single dose escalation study in six cohorts of 3–10 participants who were randomly assigned by a computer-generated table to receive 1, 2.5, 5, 10, 20, or 50 mg/kg of SAB-301 or placebo on Day 0, and were followed by clinical, laboratory, and pharmacokinetic assessments on days 1, 3, 7, 21, 42 and 90. The primary outcome was safety whereas pharmacokinetic profile, MERS virus neutralization assay over time (pharmacodynamics), and immunogenicity were secondary outcomes. The analysis was performed on the intention to treat population. ClinicalTrials.gov Identifier: NCT02788188. FINDINGS: We randomized 38 participants (28 to SAB-301 and 10 to placebo). Ninety-seven adverse event (AEs) were reported: 64 AEs occurred in 23 of 28 participants (82%) receiving SAB-301 (mean 2.3 AEs per participant), and 33 AEs occurred in 10 of 10 participants (100%) receiving placebo (mean 3.3 AEs per participant). The most common AEs were headache, albuminuria, elevated creatine kinase, and common cold, and occurred in similar proportions as placebo. Single dose pharmacokinetics (PK) demonstrated relatively linear and dose-proportional increases in maximal concentration and area-under-the-concentration-time curve (AUC(0–24)), and the PK strongly correlated with the microneutralization assay (R(2)=0.845, p