Safety and serum distribution of anti-SARS-CoV-2 monoclonal antibody MAD0004J08 after intramuscular injection
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Abstract
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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SciScore for 10.1101/2021.08.03.21261441: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: The final protocol and informed consent were approved by the institutional review boards of each of the participating investigational sites.
IRB: The final protocol and informed consent were approved by the institutional review boards of each of the participating investigational sites.
Field Sample Permit: Plasma specimens from COVID-19 convalescent and vaccinated subjects: Plasma specimens from COVID-19 convalescent subjects and SARS-COV-2 vaccinated subjects used as comparators in the present paper were previously collected from a separate study conducted in collaboration with the National Institute for Infectious Diseases, IRCCS – Lazzaro Spallanzani Rome (IT) and Azienda …SciScore for 10.1101/2021.08.03.21261441: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: The final protocol and informed consent were approved by the institutional review boards of each of the participating investigational sites.
IRB: The final protocol and informed consent were approved by the institutional review boards of each of the participating investigational sites.
Field Sample Permit: Plasma specimens from COVID-19 convalescent and vaccinated subjects: Plasma specimens from COVID-19 convalescent subjects and SARS-COV-2 vaccinated subjects used as comparators in the present paper were previously collected from a separate study conducted in collaboration with the National Institute for Infectious Diseases, IRCCS – Lazzaro Spallanzani Rome (IT) and Azienda Ospedaliera Universitaria Senese, Siena (IT).Sex as a biological variable A total of 30 healthy men and nonpregnant women, 18 to 55 years of age, meeting all inclusion/exclusion criteria were enrolled in three sequential cohorts of 10 subjects each. Randomization This is a dose escalation study, open label across doses and randomized, double blind withing each dose level. Blinding This is a dose escalation study, open label across doses and randomized, double blind withing each dose level. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources After 1 hour incubation at 37°C, 5% CO2, virus-mAb mixture was added to the wells of a 96-well plate containing a sub-confluent Vero E6 cell monolayer. Vero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources For the analyses of sera or plasma neutralisation antibody titres against SARS-CoV-2 and VoCs, the 100% inhibitory dilution (ID100) was calculated as geometric mean of two technical duplicates and statistical significances of the differences among groups was determined by non-parametric Mann–Whitney T test using GraphPad Prism software (version 8.0.2). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:The limitation of our study is that our first in human study was conducted in healthy population of age 18-55 without much diversity, whereas the risk for severity of COVID-19 disease is more in population with comorbid conditions or older age groups. Our ongoing Phase 2-3 study will assess MAD0004J08 in mild/moderate diseased and stratified subjects groups to assess dose selection and efficacy. To conclude, MAD0004J08 administration is safe, confers broad-coverage against major SARS-CoV-2 variants of concern, and giving the low dosage needed and i.m. route of administration can be a globally available and affordable countermeasure to the COVID-19 pandemic.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04932850 Active, not recruiting Study to Evaluate the Safety and Concentrations of Monoclona… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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