Abstract
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant morbidity and mortality worldwide. Despite a successful vaccination programme, the emergence of mutated variants that can escape current levels of immunity mean infections continue. Herein, we report the development of CT-P63, a broad-spectrum neutralizing monoclonal antibody. In vitro studies demonstrated potent neutralizing activity against the most prevalent variants, including Delta and the BA.1 and BA.2 sub-lineages of Omicron. In a transgenic mouse model, prophylactic CT-P63 significantly reduced wild-type viral titres in the respiratory tract and CT-P63 treatment proved efficacious against infection with Beta, Delta, and Omicron variants of SARS-CoV-2 with no detectable infectious virus in the lungs of treated animals. A randomized, double-blind, parallel-group, placebo-controlled, Phase I, single ascending dose study in healthy volunteers ( NCT05017168 ) confirmed the safety, tolerability, and pharmacokinetics of CT-P63. Twenty-four participants were randomized and received the planned dose of CT-P63 or placebo. The safety and tolerability of CT-P63 were evaluated as primary objectives. Eight participants (33.3%) experienced a treatment-emergent adverse event (TEAE), including one grade ≥3 (blood creatine phosphokinase increased). There were no deaths, treatment-emergent serious adverse events, TEAEs of special interest, or TEAEs leading to study drug discontinuation in the CT-P63 groups. Serum CT-P63 concentrations rapidly peaked before declining in a biphasic manner and systemic exposure was dose proportional. Overall, CT-P63 was clinically safe and showed broad-spectrum neutralizing activity against SARS-CoV-2 variants in vitro and in vivo .
Keywords: COVID-19; CT-P63; SARS-CoV-2 variants of concern; monoclonal antibody; neutralizing antibody.
【저자키워드】 COVID-19, SARS-CoV-2 variants of concern, monoclonal antibody, neutralizing antibody., CT-P63, 【초록키워드】 Treatment, neutralizing antibody, SARS-CoV-2, coronavirus, vaccination, pandemic, Immunity, SARS-CoV-2 variant, Infection, Delta, lung, in vitro, Prophylactic, omicron, variants, Randomized, Neutralizing activity, Beta, Placebo, Neutralizing, morbidity and mortality, respiratory tract, in vivo, placebo-controlled, Blood, monoclonal, Concentration, Infectious virus, dose, deaths, phase, Safe, double-blind, Serious Adverse Events, acute respiratory syndrome, Tolerability, treatment-emergent adverse event, study drug, parallel-group, participant, TEAE, titre, wild-type, variants of SARS-CoV-2, Transgenic mouse, creatine phosphokinase, prevalent, single ascending dose, caused, significantly, peaked, detectable, clinically, evaluated, reduced, treated, demonstrated, groups, declining, healthy volunteer, mutated variant, 【제목키워드】 neutralizing antibody, SARS-CoV-2, coronavirus, Randomized, phase, acute respiratory syndrome, Preclinical,