Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Anti-C5a Antibody BDB-001 for Severe COVID-19: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Clinical Trial in Healthy Chinese Adults

• DOI: 10.1007/s40121-023-00759-4
• Publication Date: 2023-01-25T18:03:20Z
• Authors: Guiling Chen; Nan Li; Xiahong Dai; Shiyan Tu; Zhenwei Shen; Kaiqi Wu; Tinghan Jin; Jiajun Wu; Conggao Peng; Guoping Sheng; Mengfei Zhu; Lingling Tang; Lanjuan Li
• Keywords: Tolerability; Pharmacodynamics

Severe Coronavirus Disease 2019 (COVID-19) progresses with inflammation and coagulation, due to an overactive complement system. Complement component 5a (C5a) plays a key role in the system trigger powerful "cytokine chemokine storm" viral infection. BDB-001, recombinant human immunoglobulin G4 (IgG4) that specially binds C5a, has potential inhibit C5a-triggered cytokine storm treating COVID-19 patients other diseases. Here, we have explored its safety, tolerability, pharmacokinetics, pharmacodynamics healthy adults. This trial is registered http://www.chinadrugtrials.org.cn/(CTR20200429 ).Thirty-two enrolled participants were randomized into three single-dose cohorts (2, 4, 8 mg/kg) 1 multi-dose cohort (4 mg/kg), received either BDB-001 or placebo (3:1) double-blindly. The safety tolerability after administration evaluated for 21 days 28 cohort. pharmacokinetics of plasma as free C5a analyzed.The incidence drug-related adverse events (AEs) was low, all AEs mild moderate: neither ≥ 3 (NCI-Common Terminology Criteria For Adverse Events, CTCAE 5.0) nor serious (SAEs) found. area under concentration-time curve from time zero 480 h (AUC0-480h), infinity (AUCinf), peak concentration ©max) increased dose-dependently 2 mg/kg characterized by nonlinear target-mediated drug disposal (TMDD). accumulation index AUC0-tau five administrations 6.42, suggesting effect. Furthermore, inhibition at level observed.The results this phase I study supported potent anti-C5a inhibitor no immunogenicity. TRIAL REGISTRATION NUMBER: CTR20200429.