Abstracts Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG 2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood C max and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood–pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged ( P = 0.005) and case severity ( P = 0.021), and reduced the time to virus negative ( P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.
【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, IgG, Tolerance, Coronavirus disease 2019, Efficacy, coronavirus, COVID-19 pneumonia, Pneumonia, antibody, Phase 2, SARS-COV-2 infection, severity, monoclonal antibody, pharmacokinetic characteristics, Infection, lung, pharmacokinetics, in vitro, severe acute respiratory syndrome Coronavirus, virus, Peripheral blood, CD147, Randomized, serum, Cohort, titer, Patient, Placebo, receptor, incidence, respiratory, patients, SARS-CoV-2 replication, placebo-controlled, safety profile, COVID-19 patients, Evidence, COVID-19 patient, Phase 1, phase 1 study, acute respiratory syndrome, Tolerability, treatment-emergent adverse event, control group, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, healthy volunteers, double-blinded, subject, healthy subjects, dosage, abstracts, cohorts, phase 1 trial, biodistribution study, cardiac blood–pool ratio, exploratory phase 2 study, lung tissue, Meplazumab, meplazumab treatment, TEAE, C max, positive, blocking, humanized, recent, Prevent, enrolled, evaluate, significantly, involved, indicated, conducted, eight, reduced, determine, hospitalized patient, reached, suppress, assigned, discharged, accelerate, anti-CD147, exploratory phase 2, healthy volunteer, 【제목키워드】 COVID-19, Efficacy, Trial, Safety, Randomized, exploratory phase 2, healthy volunteer,