Safety, tolerability, pharmacokinetics, and immunogenicity of an anti-SARS-CoV-2 monoclonal antibody HFB30132A after single dose intravenous administration in healthy Chinese subjects: a phase 1, randomized, double-blind, placebo-controlled study

Objective: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) still protracts worldwide. HFB30132A is an anti- SARS-CoV-2 monoclonal antibody purposely engineered for an extended half-life with neutralizing activity against majority of the virus variants identified so far. The aim of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of HFB30132A in healthy Chinese subjects. Methods: A phase 1, randomized, double-blind, placebo-controlled, single ascending dose clinical trial was designed. Twenty subjects were enrolled to Cohort 1 (1,000 mg dose level, 10 subjects) or Cohort 2 (2,000 mg dose level, 10 subjects). Subjects in each cohort were assigned randomly to receive a single intravenous (IV) dose of HFB30132A or placebo at a ratio of 8:2. Safety was assessed in terms of treatment emergent adverse events (TEAEs), vital signs, physical examination, laboratory tests, and ECG findings. PK parameters were measured and calculated appropriately. Anti-drug antibody (ADA) test was performed to detect anti-HFB30132A antibodies. Results: All subjects completed the study. Overall, 13 (65%) of the 20 subjects experienced TEAEs. The most common TEAEs were laboratory abnormalities (12 subjects [60%]), gastrointestinal disorders (6 subjects [30%]), and dizziness (4 subjects [20%]). All TEAEs were Grade 1 or Grade 2 in severity based on the criteria of Common Terminology Criteria for Adverse Events (CTCAE). Serum exposure (C-max, AUC(0-t), AUC(0-infinity)) of HFB30132A increased with ascending dose. After single dose of 1,000 mg and 2000 mg HFB30132A, the mean C-max was 570.18 mu g/mL and 898.65 mu g/mL, the mean AUC(0-t) value was 644,749.42 h*mu g/ mL and 1,046,209.06 h*mu g/mL, and the mean AUC(0-infinity) value was 806,127.47 h*mu g/ mL and 1,299,190.74 h*mu g/mL, respectively. HFB30132A showed low clearance ranging from 1.38 to 1.59 mL/h, and a long terminal elimination half-life (t (1/2)) of 89-107 days. ADA test did not detect any anti-HFB30132A antibodies Conclusion: HFB30132A was safe and generally well-tolerated after single IV dose of 1,000 mg or 2000 mg in healthy Chinese adults. HFB30132A did not induce immunogenic response in this study. Our data support further clinical development of HFB30132A.

Automated summary

The aim of this study was to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of HFB30132A in healthy Chinese adults. Results showed that HFB30132A was safe and generally well-tolerated after single IV doses of 1,000 mg or 2,000 mg, and did not induce an immunogenic response. The findings support further clinical development of HFB30132A.