A multinational, phase 2, randomised, adaptive protocol to evaluate immunogenicity and reactogenicity of different COVID-19 vaccines in adults ≥75 already vaccinated against SARS-CoV-2 (EU-COVAT-1-AGED): a trial conducted within the VACCELERATE network

Julia M Neuhann, Jannik Stemler, Antonio Carcas, Jesús Frías-Iniesta, Ullrich Bethe, Sarah Heringer, Lea Tischmann, Marouan Zarrouk, Arnd Cüppers, Franz König, Martin Posch, Oliver A Cornely, Julia M Neuhann, Jannik Stemler, Antonio Carcas, Jesús Frías-Iniesta, Ullrich Bethe, Sarah Heringer, Lea Tischmann, Marouan Zarrouk, Arnd Cüppers, Franz König, Martin Posch, Oliver A Cornely

Abstract

Background: In the ongoing COVID-19 pandemic, advanced age is a risk factor for a severe clinical course of SARS-CoV-2 infection. Thus, older people may benefit in particular from booster doses with potent vaccines and research should focus on optimal vaccination schedules. In addition to each individual's medical history, immunosenescence warrants further research in this population. This study investigates vaccine-induced immune response over 1 year.

Methods/design: EU-COVAT-1-AGED is a randomised controlled, adaptive, multicentre phase II protocol evaluating different booster strategies in individuals aged ≥75 years (n=600) already vaccinated against SARS-CoV-2. The initial protocol foresaw a 3rd vaccination (1st booster) as study intervention. The present modified Part B of this trial foresees testing of mRNA-1273 (Spikevax®) vs. BNT162b2 (Comirnaty®) as 4th vaccination dose (2nd booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 wild-type and variants. The primary endpoint of the trial is to assess the rate of 2-fold antibody titre increase 14 days after vaccination measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wild-type virus. Secondary endpoints include the changes in neutralising antibody titres (Virus Neutralisation Assay) against wild-type as well as against Variants of Concern (VOC) at 14 days and up to 12 months. T cell response measured by qPCR will be performed in subgroups at 14 days as exploratory endpoint. Biobanking samples are being collected for neutralising antibody titres against potential future VOC. Furthermore, potential correlates between humoral immune response, T cell response and neutralising capacity will be assessed. The primary endpoint analysis will be triggered as soon as for all patients the primary endpoint (14 days after the 4th vaccination dose) has been observed.

Discussion: The EU-COVAT-1-AGED trial Part B compares immunogenicity and safety of mRNA-1273 (Spikevax®) and BNT162b2 (Comirnaty®) as 4th SARS-CoV-2 vaccine dose in adults ≥75 years of age. The findings of this trial have the potential to optimise the COVID-19 vaccination strategy for this at-risk population.

Trial registration: ClinicalTrials.gov NCT05160766 . Registered on 16 December 2021.

Protocol version: V06_0: 27 July 2022.

Keywords: Advanced age; BNT162b2 (Comirnaty®); Booster; COVID-19 vaccination; Fourth dose; Immunosenescence; Phase II; Randomisation; SARS-CoV-2; VOC; Variants of concern; mRNA-1273 (Spikevax®); ≥75 years.

Conflict of interest statement

JN, no conflicts declared.

JS has received research grants by the Ministry of Education and Research (BMBF) and Basilea Pharmaceuticals Inc.; has received speaker honoraria by Pfizer Inc. and Gilead; has been a consultant to Gilead, Produkt&Markt GmbH, Alvea Vax. and Micron Research and has received travel grants by German Society for Infectious Diseases (DGI) and Meta-Alexander Foundation.

AnC, no conflicts declared.

JF has received research grants by the Instituto de Salud Carlos III, Ministry of Science. Spain. Has received grants or research contracts from Laboratorios Faes, Normon, Pfizer, Italfarmaco, GSK, Prestige, has been a consultant or has received speaker honoraria from Faes, Normon, Cinfa, Mundipharma, Abbott, Novartis and docency colaborations from Abbvie.

UB, no conflicts declared.

SH, no conflicts declared.

LT; no conflicts declared.

MZ has received honoraria for lecturing courses by Pfizer Malaysia; is now an employee with AiCuris AG.

AC, no conflicts declared.

FK, no conflicts declared.

MP, no conflicts declared

OC reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Consulting fees from Abbvie, Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, Pardes, PSI, Scynexis, Seres; Honoraria for lectures from Abbott, Al-Jazeera Pharmaceuticals, Astellas, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Pfizer; Payment for expert testimony from Cidara; Participation on a Data Safety Monitoring Board or Advisory Board from Actelion, Allecra, Cidara, Entasis, IQVIA, Janssen, MedPace, Paratek, PSI, Pulmocide, Shionogi; A patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); Other interests from DGHO, DGI, ECMM, ISHAM, MSG-ERC, Wiley.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flow chart of the trial design EU-COVAT-1-AGED Part B

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Source: PubMed

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