Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial

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 Cmax 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.