PMID- 34551869 OWN - NLM STAT- MEDLINE DCOM- 20211203 LR - 20211214 IS - 1879-114X (Electronic) IS - 0149-2918 (Print) IS - 0149-2918 (Linking) VI - 43 IP - 10 DP - 2021 Oct TI - Safety, Virologic Efficacy, and Pharmacokinetics of CT-P59, a Neutralizing Monoclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Protein: Two Randomized, Placebo-Controlled, Phase I Studies in Healthy Individuals and Patients With Mild SARS-CoV-2 Infection. PG - 1706-1727 LID - S0149-2918(21)00308-8 [pii] LID - 10.1016/j.clinthera.2021.08.009 [doi] AB - PURPOSE: Neutralizing antibodies can reduce SARS-CoV-2 cellular entry, viral titers, and pathologic damage. CT-P59 (regdanvimab), a SARS-CoV-2 neutralizing monoclonal antibody, was examined in 2 randomized, double-blind, placebo-controlled, single ascending dose, Phase I studies. METHODS: In study 1.1, healthy adults were sequentially enrolled to receive CT-P59 10, 20, 40, or 80 mg/kg or placebo. In study 1.2, adult patients with mild SARS-CoV-2 infection were enrolled to receive CT-P59 20, 40, or 80 mg/kg or placebo. Primary objectives of both studies were safety and tolerability up to day 14 after infusion. Secondary end points included pharmacokinetic properties. Study 1.2 also measured virology and clinical efficacy. FINDINGS: Thirty-two individuals were randomized to study 1.1 (6 per CT-P59 dose cohort and 8 in the placebo cohort). By day 14 after infusion, adverse events (AEs) were reported in 2 individuals receiving CT-P59 20 mg/kg (headache and elevated C-reactive protein levels) and 1 receiving CT-P59 40 mg/kg (pyrexia) (all Common Terminology Criteria for Adverse Events grade 1). In study 1.2, 18 patients were randomized (5 per dose cohort and 3 in the placebo cohort). Sixteen AEs were reported in 10 patients receiving CT-P59. No AEs in either study led to study discontinuation. Greater reductions in viral titers were reported with CT-P59 than placebo in those with maximum titers >10(5) copies/mL. Mean time to recovery was 3.39 versus 5.25 days. IMPLICATIONS: CT-P59 exhibited a promising safety profile in healthy individuals and patients with mild SARS-CoV-2 infection, with potential antiviral and clinical efficacy in patients with mild SARS-CoV-2 infection. ClinicalTrials.gov identifier: NCT04525079 (study 1.1) and NCT04593641 (study 1.2). CI - Copyright (c) 2021. Published by Elsevier Inc. FAU - Kim, Jin Yong AU - Kim JY AD - Division of Infectious Diseases, Department of Internal Medicine, Incheon Medical Center, Incheon, Republic of Korea. FAU - Jang, Young Rock AU - Jang YR AD - Division of Infectious Diseases, Department of Internal Medicine, Incheon Medical Center, Incheon, Republic of Korea. FAU - Hong, Jang Hee AU - Hong JH AD - Clinical Trials Center, Chungnam National University Hospital, Daejeon, Republic of Korea. FAU - Jung, Jin Gyu AU - Jung JG AD - Clinical Trials Center, Chungnam National University Hospital, Daejeon, Republic of Korea. FAU - Park, Jae-Hyeong AU - Park JH AD - Clinical Trials Center, Chungnam National University Hospital, Daejeon, Republic of Korea. FAU - Streinu-Cercel, Adrian AU - Streinu-Cercel A AD - National Institute for Infectious Diseases "Prof. Dr. Matei Bals," Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. FAU - Streinu-Cercel, Anca AU - Streinu-Cercel A AD - National Institute for Infectious Diseases "Prof. Dr. Matei Bals," Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. FAU - Sandulescu, Oana AU - Sandulescu O AD - National Institute for Infectious Diseases "Prof. Dr. Matei Bals," Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. FAU - Lee, Sang Joon AU - Lee SJ AD - Celltrion Inc, Incheon, Republic of Korea. FAU - Kim, Sung Hyun AU - Kim SH AD - Celltrion Inc, Incheon, Republic of Korea. FAU - Jung, Na Hyun AU - Jung NH AD - Celltrion Inc, Incheon, Republic of Korea. FAU - Lee, Seul Gi AU - Lee SG AD - Celltrion Inc, Incheon, Republic of Korea. FAU - Park, Jeong Eun AU - Park JE AD - Celltrion Inc, Incheon, Republic of Korea. FAU - Kim, Min Kyung AU - Kim MK AD - Celltrion Inc, Incheon, Republic of Korea. FAU - Jeon, Da Bee AU - Jeon DB AD - Celltrion Inc, Incheon, Republic of Korea. FAU - Lee, Yeo Jin AU - Lee YJ AD - Celltrion Inc, Incheon, Republic of Korea. FAU - Kim, Bum Soo AU - Kim BS AD - Celltrion Inc, Incheon, Republic of Korea. FAU - Lee, Yeon Mi AU - Lee YM AD - Celltrion Inc, Incheon, Republic of Korea. FAU - Kim, Yeon-Sook AU - Kim YS AD - Division of Infectious Diseases, Chungnam National University School of Medicine, Daejeon, Republic of Korea. Electronic address: alice@cnuh.co.kr. LA - eng SI - ClinicalTrials.gov/NCT04525079 SI - ClinicalTrials.gov/NCT04593641 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210823 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antibodies, Neutralizing) RN - 0 (Carrier Proteins) RN - 0 (Immunoglobulin G) RN - I0BGE6P6I6 (regdanvimab) SB - IM MH - Adult MH - Antibodies, Monoclonal/adverse effects MH - Antibodies, Monoclonal, Humanized MH - Antibodies, Neutralizing MH - *COVID-19 MH - Carrier Proteins MH - Double-Blind Method MH - Humans MH - Immunoglobulin G MH - *SARS-CoV-2 PMC - PMC8380488 OTO - NOTNLM OT - COVID-19 OT - CT-P59 OT - SARS-CoV-2 OT - neutralizing monoclonal antibody OT - regdanvimab EDAT- 2021/09/24 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/08/23 CRDT- 2021/09/23 05:45 PHST- 2021/05/13 00:00 [received] PHST- 2021/07/23 00:00 [revised] PHST- 2021/08/18 00:00 [accepted] PHST- 2021/09/24 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/09/23 05:45 [entrez] PHST- 2021/08/23 00:00 [pmc-release] AID - S0149-2918(21)00308-8 [pii] AID - 10.1016/j.clinthera.2021.08.009 [doi] PST - ppublish SO - Clin Ther. 2021 Oct;43(10):1706-1727. doi: 10.1016/j.clinthera.2021.08.009. Epub 2021 Aug 23.