tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2022 Aug 25;1-39.
doi: 10.1080/22221751.2022.2117094. Online ahead of print.
Preclinical assessment and randomized Phase I study of CT-P63, a broadly neutralizing antibody targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Ji-Min Seo[SUP] 1 [/SUP], Bobin Kang[SUP] 1 [/SUP], Rina Song[SUP] 1 [/SUP], Hanmi Noh[SUP] 1 [/SUP], Cheolmin Kim[SUP] 1 [/SUP], Jong-In Kim[SUP] 1 [/SUP], Minsoo Kim[SUP] 1 [/SUP], Dong-Kyun Ryu[SUP] 1 [/SUP], Min-Ho Lee[SUP] 2 [/SUP], Jeong-Sun Yang[SUP] 3 [/SUP], Kyung-Chang Kim[SUP] 3 [/SUP], Joo-Yeon Lee[SUP] 3 [/SUP], Hansaem Lee[SUP] 3 [/SUP], Hye-Min Woo[SUP] 3 [/SUP], Jun-Won Kim[SUP] 3 [/SUP], Jung-Ah Choi[SUP] 4 [/SUP], Manki Song[SUP] 4 [/SUP], Monika Tomaszewska-Kiecana[SUP] 5 [/SUP], Anna Wołowik[SUP] 5 [/SUP], Agnieszka Kulesza[SUP] 5 [/SUP], Sunghyun Kim[SUP] 1 [/SUP], Keumyoung Ahn[SUP] 1 [/SUP], Nahyun Jung[SUP] 1 [/SUP], Soo-Young Lee[SUP] 1 [/SUP]
Affiliations
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.
. 2022 Aug 25;1-39.
doi: 10.1080/22221751.2022.2117094. Online ahead of print.
Preclinical assessment and randomized Phase I study of CT-P63, a broadly neutralizing antibody targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Ji-Min Seo[SUP] 1 [/SUP], Bobin Kang[SUP] 1 [/SUP], Rina Song[SUP] 1 [/SUP], Hanmi Noh[SUP] 1 [/SUP], Cheolmin Kim[SUP] 1 [/SUP], Jong-In Kim[SUP] 1 [/SUP], Minsoo Kim[SUP] 1 [/SUP], Dong-Kyun Ryu[SUP] 1 [/SUP], Min-Ho Lee[SUP] 2 [/SUP], Jeong-Sun Yang[SUP] 3 [/SUP], Kyung-Chang Kim[SUP] 3 [/SUP], Joo-Yeon Lee[SUP] 3 [/SUP], Hansaem Lee[SUP] 3 [/SUP], Hye-Min Woo[SUP] 3 [/SUP], Jun-Won Kim[SUP] 3 [/SUP], Jung-Ah Choi[SUP] 4 [/SUP], Manki Song[SUP] 4 [/SUP], Monika Tomaszewska-Kiecana[SUP] 5 [/SUP], Anna Wołowik[SUP] 5 [/SUP], Agnieszka Kulesza[SUP] 5 [/SUP], Sunghyun Kim[SUP] 1 [/SUP], Keumyoung Ahn[SUP] 1 [/SUP], Nahyun Jung[SUP] 1 [/SUP], Soo-Young Lee[SUP] 1 [/SUP]
Affiliations
- PMID: 36006772
- DOI: 10.1080/22221751.2022.2117094
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.