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 1 Studies in Healthy Subjects and Patients with Mild SARS-CoV-2 Infection

Kim, Jin Yong; Jang, Young Rock; Hong, Jang Hee; Jung, Jin Gyu; Park, Jae-Hyeong; Streinu-Cercel, Adrian; Streinu-Cercel, Anca; Săndulescu, Oana; Lee, Sang Joon; Kim, Sung Hyun; Jung, Na Hyun; Lee, Seul Gi; Park, Jeong Eun; Kim, Min Kyung; Jeon, Da Bee; Lee, Yeo Jin; Kim, Bum Soo; Lee, Yeon Mi; Kim, Yeon-Sook

PURPOSE: Neutralizing antibodies can reduce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, viral titers, and pathological damage. CT-P59 (regdanvimab), a SARS-CoV-2 neutralizing monoclonal antibody, was examined in 2 randomized, double-blind, placebo-controlled, single ascending dose, phase 1 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 post-infusion. Secondary endpoints included pharmacokinetics. Study 1.2 also measured virology and clinical efficacy. FINDINGS: Thirty-two subjects were randomized to study 1.1 (6 per CT-P59 dose cohort; 8 placebo). By day 14 post-infusion, adverse events (AEs) were reported in 2 subjects receiving CT-P59 20 mg/kg (headache, elevated C-reactive protein) and 1 receiving CT-P59 40 mg/kg (pyrexia); all CTCAE grade 1. In study 1.2, 18 patients were randomized (5 per dose cohort; 3 placebo). 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, respectively. IMPLICATIONS: CT-P59 exhibited a promising safety profile in healthy subjects and patients with mild SARS-CoV-2 infection, with potential antiviral and clinical efficacy in patients with mild SARS-CoV-2 infection. TRIAL REGISTRATION: Study 1.1: EudraCT, 2020-003065-19; NCT04525079. Study 1.2: EudraCT, 2020-003165-19; NCT04593641.