TY - JOUR
T1 - Safety and serum distribution of anti-SARS-CoV-2 monoclonal antibody MAD0004J08 after intramuscular injection
AU - Lanini, Simone
AU - Milleri, Stefano
AU - Andreano, Emanuele
AU - Nosari, Sarah
AU - Paciello, Ida
AU - Piccini, Giulia
AU - Gentili, Alessandra
AU - Phogat, Adhuna
AU - Hyseni, Inesa
AU - Leonardi, Margherita
AU - Torelli, Alessandro
AU - Montomoli, Emanuele
AU - Paolini, Andrea
AU - Frosini, Andrea
AU - Antinori, Andrea
AU - Nicastri, Emanuele
AU - Girardi, Enrico
AU - Plazzi, Maria Maddalena
AU - Ippolito, Giuseppe
AU - Vaia, Francesco
AU - Della Cioppa, Giovanni
AU - Rappuoli, Rino
N1 - Funding Information:
The authors would like to thank the donors, physicians, and staff participating in this phase I clinical trial aimed to evaluate the safety and tolerability of MAD0004J08. We would also like to thank CROss Allience, Mendrisio, Svizzera, Ardena Bioanalyses, Assen, Netherlands, ExcellGene, Monthey, Switzerland, Menarini Biotech S.r.l., Pomezia, Italy and Istituto Biochimico Italiano (IBI) Lorenzini, Aprilia, Italy, for their support to this study. The authors would also like to acknowledge Concetta Castelletti (laboratory), clinical team: Ilaria Mastrorosa, Alessandra Vergori, Sandrine Ottou, Serena Vita, Laura Scorzolini, Alessandra D’Abramo. This study was supported by the EU Malaria Fund, inaugurated on the 3rd of June 2020 and initiated by the kENUP Foundation. This publication was supported by the COVID-2020-12371817 project, which has received funding from the Italian Ministry of Health (Ministero della Salute), from the Italian Ministry of Economic (Ministero dello Sviluppo Economico) through the “Contratti di Sviluppo” funding program, and from Regione Toscana. This work was funded by the European Research Council (ERC) advanced grant agreement number 787552 (vAMRes). This publication was supported by the European Virus Archive goes Global (EVAg) project, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 653316.
Funding Information:
The authors would like to thank the donors, physicians, and staff participating in this phase I clinical trial aimed to evaluate the safety and tolerability of MAD0004J08. We would also like to thank CROss Allience, Mendrisio, Svizzera, Ardena Bioanalyses, Assen, Netherlands, ExcellGene, Monthey, Switzerland, Menarini Biotech S.r.l., Pomezia, Italy and Istituto Biochimico Italiano (IBI) Lorenzini, Aprilia, Italy, for their support to this study. The authors would also like to acknowledge Concetta Castelletti (laboratory), clinical team: Ilaria Mastrorosa, Alessandra Vergori, Sandrine Ottou, Serena Vita, Laura Scorzolini, Alessandra D?Abramo. This study was supported by the EU Malaria Fund, inaugurated on the 3rd of June 2020 and initiated by the kENUP Foundation. This publication was supported by the COVID-2020-12371817 project, which has received funding from the Italian Ministry of Health (Ministero della Salute), from the Italian Ministry of Economic (Ministero dello Sviluppo Economico) through the ?Contratti di Sviluppo? funding program, and from Regione Toscana. This work was funded by the European Research Council (ERC) advanced grant agreement number 787552 (vAMRes). This publication was supported by the European Virus Archive goes Global (EVAg) project, which has received funding from the European Union?s Horizon 2020 research and innovation program under grant agreement No 653316.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-29909-x
DO - 10.1038/s41467-022-29909-x
M3 - Article
C2 - 35477725
AN - SCOPUS:85128966723
SN - 2041-1723
VL - 13
SP - 1
EP - 8
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2263
ER -