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

Abstract

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 >10⁵ 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).

Keywords: COVID-19; CT-P59; SARS-CoV-2; neutralizing monoclonal antibody; regdanvimab.

Figure 1

Participant flow diagrams for study 1.1 (A) and study 1.2 (B).

Figure 2

Mean serum concentrations of CT-P59 in healthy volunteers (study 1.1). Data are presented on a semilogarithmic scale shown as an insert. Error bars indicate SDs.

Figure 3

Change in viral titer according to maximum viral load (A) <10⁵ copies (cp)/mL, (B) >10⁵ cp/mL, (C) >10⁶ cp/mL, and (D) >10⁷ cp/mL in patients with mild SARS-CoV-2 infection (study 1.2). Dotted horizontal lines represent lower limit of detection.

Figure 4

Serum concentrations of CT-P59 in patients with mild SARS-CoV-2 infection (study 1.2). Data are presented on a semilogarithmic scale shown as an insert. Error bars indicate SDs.