Population pharmacokinetics and pharmacodynamics of HFB30132A, a monoclonal antibody against SARS-CoV-2, in healthy Chinese and US subjects.

Development of neutralizing monoclonal antibody (nAb) is a strategy for treatment of infections caused by SARS-CoV-2. This study evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of HFB30132A, a fully human nAb targeting SARS-CoV-2 spike protein receptor binding domain, in healthy subjects. Randomized, double-blind, placebo-controlled phase I trial was performed in healthy Chinese and US subjects, respectively. The subjects (n=44) received a single ascending dose (400, 1000, 2000 mg) or placebo. Safety and PK data were analysed. PD was evaluated by pseudovirus neutralization test in vitro using serum samples of Chinese subjects. Population PK/PD model was developed using non-linear mixed effects modeling. Effect of covariates was evaluated via covariate screening, Monte Carlo simulation, and randomisation test. The PK profile was consistent with three-compartment model. The clearance (CL) and V₁ were 0.38 mL/h and 2.9 L, respectively. Ethnicity and body weight (BW) were factors affecting PK. Compared to the subjects who are not Hispanic or Latino, AUC_0-∞ increased by 64% in the healthy subjects of Han nationality. The PD was consistent with effect-compartment model when ND₅₀ titre (reciprocal of 50% neutralization dilution) was used as PD index. E_max reduced along with time, consistent with exponential model. The EC₅₀ was 4590 mg/L. Half-life for reduction of E_max was 133 days. Albumin, lymphocytes, neutrophils or monocytes were covariates on PD. There was ethnic difference in PK, and tolerance in PD of HFB30132A. Population PK/PD model characterized dose-exposure-response relationship of HFB30132A in healthy subjects. These findings are useful for drug development in the future. Clinical trial registration: ClinicalTrial.gov NCT04590430, NCT05275660.