Safety and serum distribution of anti-SARS-CoV-2 monoclonal antibody MAD0004J08 after intramuscular injection

• Published in: Nature communications 2022-04, Vol.13 (1), p.2263-8, Article 2263
• Main Authors: Lanini, Simone, Milleri, Stefano, Andreano, Emanuele, Nosari, Sarah, Paciello, Ida, Piccini, Giulia, Gentili, Alessandra, Phogat, Adhuna, Hyseni, Inesa, Leonardi, Margherita, Torelli, Alessandro, Montomoli, Emanuele, Paolini, Andrea, Frosini, Andrea, Antinori, Andrea, Nicastri, Emanuele, Girardi, Enrico, Plazzi, Maria Maddalena, Ippolito, Giuseppe, Vaia, Francesco, Della Cioppa, Giovanni, Rappuoli, Rino
• Format: Article
• Language: English
• Subjects: 631/250/2152/2153/1291; 631/326/596/4130; 692/308/153; 692/308/2779/109/1940; 82/1; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - blood; Antibodies, Viral; Coronaviruses; COVID-19; Humanities and Social Sciences; Humans; Injections, Intramuscular; Monoclonal antibodies; multidisciplinary; Neutralization; Neutralization Tests; Pharmacokinetics; Pharmacology; Prophylaxis; Safety; SARS-CoV-2 - immunology; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Vaccination
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-29909-x

The emerging threat represented by SARS-CoV-2 variants, demands the development of therapies for better clinical management of COVID-19. MAD0004J08 is a potent Fc-engineered monoclonal antibody (mAb) able to neutralize in vitro all current SARS-CoV-2 variants of concern (VoCs) including the omicron variant even if with significantly reduced potency. Here we evaluated data obtained from the first 30 days of a phase 1 clinical study (EudraCT N.: 2020-005469-15 and ClinicalTrials.gov Identifier: NCT04932850). The primary endpoint evaluated the percentage of severe adverse events. Secondary endpoints evaluated pharmacokinetic and serum neutralization titers. A single dose administration of MAD0004J08 via intramuscular ( i.m .) route is safe and well tolerated, resulting in rapid serum distribution and sera neutralizing titers higher than COVID-19 convalescent and vaccinated subjects. A single dose administration of MAD0004J08 is also sufficient to effectively neutralize major SARS-CoV-2 variants of concern (alpha, beta, gamma and delta). MAD0004J08 can be a major advancement in the prophylaxis and clinical management of COVID-19. Monoclonal antibodies (mAbs) are a potential therapeutic option for treatment of COVID-19. Here, the authors report safety and pharmacokinetics of an intramuscularly injected mAb (MAD0004J08) during the first 30 days of a phase 1 clinical study.