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
| Autor: | Jin Gyu Jung, Sunghyun Kim, Bum Soo Kim, Anca Streinu-Cercel, Oana Săndulescu, Da Bee Jeon, Adrian Streinu-Cercel, Seul Gi Lee, Sang Joon Lee, Yeon Sook Kim, Yeo Jin Lee, Jin Yong Kim, Yeon Mi Lee, Min Kyung Kim, Jae-Hyeong Park, Jang Hee Hong, Jeong Eun Park, Young Rock Jang, Na Hyun Jung |
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| Rok vydání: | 2021 |
| Předmět: |
CTCAE
Common Toxicity Criteria for Adverse Events BMI body mass index Cmax/dose dose-normalized maximum serum concentration Gastroenterology CPK creatine phosphokinase regdanvimab Pharmacology (medical) Original Research COVID-19 coronavirus disease 2019 AUC0–inf area under the serum concentration–time curve from time zero to infinity biology ADE antibody-dependent enhancement Antibodies Monoclonal EudraCT European Union Drug Regulating Authorities Clinical Trials Database RBD receptor-binding domain Common Terminology Criteria for Adverse Events CL total body clearance IRR infusion-related reaction Vz volume of distribution during the terminal phase Tolerability t½ terminal elimination half-life Cohort CRP C-reactive protein Antibody ADA anti-drug antibody AE adverse event Adult CT-P59 medicine.medical_specialty Antibodies Monoclonal Humanized ACE2 angiotensin-converting enzyme 2 Placebo SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 DEC Dose Escalation Committee S spike [protein] Double-Blind Method MedDRA Medical Dictionary for Regulatory Activities Pharmacokinetics ALT alanine aminotransferase Internal medicine medicine Humans Adverse effect RT-PCR reverse transcription–polymerase chain reaction IQR interquartile range Pharmacology SAE serious adverse event SE standard error SARS-CoV-2 business.industry COVID-19 RT-qPCR quantitative reverse transcription–polymerase chain reaction Antibodies Neutralizing Discontinuation CI confidence interval AUC0–inf/dose dose-normalized area under the serum concentration–time curve from time zero to infinity Neutralizing monoclonal antibody cp copies Immunoglobulin G Ct cycle threshold biology.protein Cmax maximum serum concentration Tmax time to maximum serum concentration Carrier Proteins SD standard deviation business |
| Zdroj: | Clinical Therapeutics |
| ISSN: | 0149-2918 |
| DOI: | 10.1016/j.clinthera.2021.08.009 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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