Preclinical assessment and randomized Phase I study of CT-P63, a broadly neutralizing antibody targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

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
• SARS-CoV-2 variants of concern
• neutralizing antibody
• monoclonal antibody
• CT-P63

Acknowledgements

We thank all participants and investigators involved in the study. Medical writing support, including development of a draft outline and subsequent drafts in consultation with the authors, collating author comments, copyediting, fact checking, and referencing, was provided by Beatrice Tyrrell, DPhil, at Aspire Scientific Limited (Bollington, UK). Funding for medical writing support for this article was provided by Celltrion, Inc. (Incheon, Republic of Korea).

Disclosure statement

J.M.S., R.S., B.K., H.N., C.K., J.I.K., M.K., D.K.R., S.K., K.A., N.J., and S.Y.L. are employees of Celltrion, Inc. M.T-K., A.W., A.K are employees of Biokinetica which was sponsored by Celltrion, Inc., for conduct of this study. M.H.L., J.S.Y., K.C.K., J.Y.L., H.L., H.M.W., J.W.K., J.A.C., M.S. report no potential conflict of interest.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Additional information

Funding

This research was partly funded by Korea National Institute of Health (KNIH) [grant numbers 2021-NI007-01, 2021-ER1601-00, and 2020-ER5337-00]. This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, South Korea [grant number HQ21C0193]. The Phase I study was funded by Celltrion (Incheon, Republic of Korea).