A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Clinical Trial to Assess Safety, Tolerability, and Pharmacokinetics of LY-CovMab, a Potent Human Neutralizing Antibody Against SARS-CoV-2

Introduction We aimed to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of a single dose of LY-CovMab in Chinese healthy adults. Methods We conducted a phase 1, randomized, dose-escalation, placebo-controlled trial in 42 volunteers, 18-45 years of age, and 40 out of 42 received a single dose of LY-CovMab or placebo with LY-CovMab at a dose of 30 mg, 150 mg, 600 mg, 1200 mg, and 2400 mg. There were ten subjects in each group receiving LY-CovMab or placebo in a 4:1 ratio with the exception that the 30 mg group had two subjects both receiving LY-CovMab. Results Among the 42 randomized participants, 40 received an injection with 32 administered LY-CovMab and 8 administered placebo. A total of 18 drug-related treatment-emergent adverse events (TEAEs) were reported in 12 subjects (30.0%), including protein urine present (25%, 10/40) and blood creatinine increased (7.5%, 3/40). The incidence of drug-related TEAE in each dosage group was as follows: 150 mg (28.6%, 2/7), 600 mg (25%, 2/8), 1200 mg (14.3%, 1/7), 2400 mg (50%, 4/8), and placebo (37.5%, 3/8). All drug-related TEAEs were grade 1, and most of them were recovering/resolving or recovered/resolved without taking action. The serum exposure of LY-CovMab (C-max, AUC(0-last), AUC(0-inf)) after intravenous infusion increased in an approximately proportional manner as the dose increased from 150 to 2400 mg. The elimination half-life (t(1/2)) value did not differ among different dose cohorts and was estimated to be around 28.5 days. Conclusions A single dose of LY-CovMab was shown to be safe and well tolerated in Chinese healthy adults. The pharmacokinetic (PK) profiles of LY-CovMab in healthy adults showed typical monoclonal antibody distribution and elimination characteristics. LY-CovMab demonstrated dose proportionality.