Assessing Immune Response of Different COVID-19 Vaccines in Older Adults (EU-COVAT-1)

A Multinational, Phase 2, Randomised, Adaptive Protocol to Evaluate Immunogenicity and Reactogenicity of Different COVID-19 Vaccines Administration in Older Adults (≥75) Already Vaccinated Against SARS-COV-2 (EU-COVAT-1_AGED)

This is a randomised controlled, adaptive, multicentre Phase II protocol evaluating different booster strategies in individuals aged 75 years and older already vaccinated against SARS-CoV-2.

Part A of this trial foresees testing of different vaccines as a 3rd vaccination dose (first booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 wild-type and variants in the elderly, a usually neglected population.

Part B of this trial foresees testing of different vaccines as a 4th vaccination dose (second booster) for comparative assessment of their immunogenicity and safety against SARSCoV-2 wild-type and variants in the identical population.

Study Overview

• Status: Completed
• Conditions: Prevention of COVID-19
• Intervention / Treatment: Biological: Comirnaty (BTN162b2); Biological: Spikevax (mRNA-1273)

Detailed Description

Part A of the present trial in which individuals received a 3rd vaccination (first booster) of either BNT162b2 or mRNA-1273 was closed to further recruitment as of January 13, 2022. This was due to a change in vaccination policies, recommending a 3rd vaccination with either BNT162b2 or mRNA-1273. Therefore, Part A was supplanted by Part B that investigated a 4th COVID-19 vaccination and started on 21 Jan 2022.

The initial study protocol started the trial with Part A in which participants were randomized to a 3rd vaccination (first booster) with either BNT162b2 or mRNA-1273:

Subjects who - prior to study entry - received a vaccination series of either BNT162b2 & BNT162b2 or mRNA-1273 & mRNA-1273 or ChAdOx-1-S & ChAdOx-1-S.

For the reasons mentioned above, the study protocol was amended to continue the trial with Part B in which participants were randomized to a 4th vaccination (second booster) with either BNT162b2 or mRNA-1273:

Subjects who - prior to study entry - received a vaccination series of either BNT162b2 & BNT162b2 & BNT162b2 or BNT162b2 & BNT162b2 & mRNA-1273 or mRNA-1273 & mRNA-1273 & mRNA-1273 or mRNA-1273 & mRNA-1273 & BNT162b2 or ChAdOx-1-S & ChAdOx-1-S & BNT162b2 or ChAdOx-1-S & ChAdOx-1-S & mRNA-1273.

• Study Type: Interventional
• Enrollment (Actual): 323
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Cologne, Germany, 50931
    • University Hospital Cologne
  • Frankfurt, Germany, 60590
    • University Hospital Frankfurt
  • Hannover, Germany, 30625
    • Hannover Medical School Hospital
• Lithuania
  • Vilnius, Lithuania, 08661
    • Vilnius University Hospital Santaros Klinikos
• Norway
  • Bergen, Norway, 5021
    • Helse Bergen HF, Haukeland University Hospital
• Spain
  • Badalona, Spain, 08916
    • Hospital Universitari Germans Trias i Pujol
  • Córdoba, Spain, 14004
    • Reina Sofia University Hospital
  • Madrid, Spain, 28046
    • La Paz University Hospital
  • San Sebastián, Spain, 20014
    • Biodonostia Health Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria (Part A):

• Subject is ≥75 years old.
• Prior to study entry the subject was vaccinated with BNT162b2, mRNA-1273 or ChAdOx-1-S (same vaccine product for 1st + 2nd dose)

BNT162b2 + BNT162b2

mRNA-1273 + mRNA-1273

ChAdOx-1-S + ChAdOx-1-S

• 9 ± 3 months since the second vaccine dose at time of enrolment for the planned 3rd vaccine dose in the trial. Vaccination status should be documented in the source data and captured in the eCRF.
• No contra-indication against any of the vaccine products in the trial.
• Written informed consent from subject has been obtained.

Exclusion Criteria (Part A):

• Primary vaccination performed with different vaccine products as sole (e.g., COVID-19 Vaccine Janssen) or, 1st and 2nd vaccination doses (heterologous vaccination scheme).
• Subjects with any significant or uncontrolled disease posing a risk due to vaccination as judged by the investigator.
• Current immunosuppressive therapy, for example continuous glucocorticosteroid treatment equivalent to >10 mg/day prednisolone.
• Participation in other interventional trials.
• Subjects unable to report solicited adverse events.
• Subject with any contraindications to the vaccines in the trial at randomisation. A list of contraindications as listed in the Summary of medicinal Product Characteristics (SmPC, the Fachinformation in Germany), if appropriate.
• Use of drugs with significant interaction with the investigational product according to the SmPC or similar documents.
• Diseases or findings that may have a significant effect on the target variables and which may therefore mask or inhibit the therapeutic effect under investigation.
• Any current SARS-CoV-2 infection or proven in the preceding 3 months.
• Persons with any kind of dependency on the principal investigator or employed by the sponsor or principal investigator.
• Legally incapacitated persons.
• Persons held in an institution by legal or official order.

Inclusion Criteria (Part B):

• Subject is ≥75 years old.
• Prior to study entry the subject was vaccinated with one of the following vaccination regimens (1st + 2nd + 3rd dose):

BNT162b2 + BNT162b2 + BNT162b2

BNT162b2 + BNT162b2 + mRNA-1273

mRNA-1273 + mRNA-1273 + mRNA-1273

mRNA-1273 + mRNA-1273 + BNT162b2

ChAdOx-1-S + ChAdOx-1-S + BNT162b2

ChAdOx-1-S + ChAdOx-1-S + mRNA-1273

The last dose of the above listed vaccinations must have been administered at least 1 month prior to study entry. Vaccination status should be documented in the source data and will be captured in the eCRF.

- Written informed consent from subject has been obtained.

Exclusion Criteria (Part B):

• Prior to study entry the subject got vaccinated with a regimen not included in the list given above.
• Last anti-SARS-CoV-2 vaccine dose administered less than one month prior to study entry.
• Vaccination against a disease other than COVID-19 within 2 weeks prior to study entry. Only exception: Influenza vaccination which is allowed at any time.
• Subjects with any significant or uncontrolled disease posing a risk due to vaccination as judged by the investigator.
• Current immunosuppressive therapy, for example continuous glucocorticosteroid treatment equivalent to >10 mg/day prednisolone.
• Subject simultaneously participates in another clinical trials or has participated in the past 30 days.
• Subjects unable to report solicited adverse events.
• Subject with any contraindications to the vaccines in the trial. A list of contraindications as listed in the Summary of medicinal Product Characteristics (SmPC, the Fachinformation in Germany), if appropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: BNT162b2 (Part A); vaccination with BNT162b2 as 3rd vaccination	Biological: Comirnaty (BTN162b2); Single booster shot (3rd dose in Part A and 4th dose in Part B)
Active Comparator: mRNA-1273 (Part A); vaccination with mRNA-1273 as 3rd vaccination	Biological: Spikevax (mRNA-1273); Single booster shot (3rd dose in Part A and 4th dose in Part B)
Active Comparator: BNT162b2 (Part B); vaccination with BNT162b2 as 4th vaccination	Biological: Comirnaty (BTN162b2); Single booster shot (3rd dose in Part A and 4th dose in Part B)
Active Comparator: mRNA-1273 (Part B); vaccination with mRNA-1273 as 4th vaccination	Biological: Spikevax (mRNA-1273); Single booster shot (3rd dose in Part A and 4th dose in Part B)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody Titre Increase 14 Days After Study Vaccination Dose.	Rate of 2-fold antibody titre increase 14 days after 3rd (Part A) or 4th vaccination dose (Part B) measured by qualitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wildtype virus.	From Day 0 until Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Neutralizing Antibody Titre Against Wild-type 14 Days After Study Vaccination Dose	Change in neutralizing antibody titre (Virus Neutralisation Assay) against wild-type 14 days after a 3rd (Part A) or 4th vaccination dose (Part B), to be determined in a subgroup only. Microneutralization assay results were proposed to be reported as "change in neutralizing antibody titre (Virus Neutralisation Assay)" in the trial protocol. However, as the pandemic progressed, the need arose to assess neutralization against different variants. In our stud(ies), we evaluated not only the Wuhan strain but also 25 distinct variants of concern (VoCs) and/or variants of interest (VoIs). For VoCs and VoIs, expressing results as "change in neutralization capacity expressed as a percentage (%)" is more effective as it illustrates the impact of mutations on neutralization, thereby allowing cross-variant comparisons. This adjustment did not alter the suggested endpoint, as both reporting methods reflect the ability of patients' antibodies neutralizing capacities.	From Day 0 until Day 14
Change in Neutralizing Antibody Titre Against Variants of Concern 14 Days After Study Vaccination Dose	Change in neutralizing antibody titre (Virus Neutralisation Assay) against variants of concern 14 days after a 3rd (Part A) or 4th vaccination dose (Part B), to be determined in a subgroup only. Microneutralization assay results were proposed to be reported as "change in neutralizing antibody titre (Virus Neutralisation Assay)" in the trial protocol. However, as the pandemic progressed, the need arose to assess neutralization against different variants. In our stud(ies), we evaluated not only the Wuhan strain but also 25 distinct variants of concern (VoCs) and/or variants of interest (VoIs). For VoCs and VoIs, expressing results as "change in neutralization capacity expressed as a percentage (%)" is more effective as it illustrates the impact of mutations on neutralization, thereby allowing cross-variant comparisons. This adjustment did not alter the suggested endpoint, as both reporting methods reflect the ability of patients' antibodies neutralizing capacities.	From Day 0 until Day 14
Antibody Titre Level at 12 Months After a Study Vaccination Dose	Antibody titre level at 12 months after a 3rd (Part A) or 4th vaccination dose (Part B) measured by a quantitative enzyme-linked immunosorbent assay (anti-RBD-ELISA assay).	From Day 0 until Month 12
Neutralizing Antibody Titre Against Wild-type at 12 Months After Study Vaccination Dose	Neutralizing antibody titre (Virus Neutralisation Assay) against wild-type SARS-CoV-2 at 12 months after a 3rd (Part A) or 4th vaccination dose (Part B), to be determined in a subgroup only. Microneutralization assay results were proposed to be reported as "change in neutralizing antibody titre (Virus Neutralisation Assay)" in the trial protocol. However, as the pandemic progressed, the need arose to assess neutralization against different variants. In our stud(ies), we evaluated not only the Wuhan strain but also 25 distinct variants of concern (VoCs) and/or variants of interest (VoIs). For VoCs and VoIs, expressing results as "change in neutralization capacity expressed as a percentage (%)" is more effective as it illustrates the impact of mutations on neutralization, thereby allowing cross-variant comparisons. This adjustment did not alter the suggested endpoint, as both reporting methods reflect the ability of patients' antibodies neutralizing capacities.	From Day 0 until Month 12
Neutralizing Antibody Titre Against Variants of Concern at 12 Months After Study Vaccination Dose	Neutralizing antibody titre (Virus Neutralisation Assay) against variants of concern at 12 months after a 3rd (Part A) or 4th vaccination dose (Part B), to be determined in a subgroup only. Microneutralization assay results were proposed to be reported as "change in neutralizing antibody titre (Virus Neutralisation Assay)" in the trial protocol. However, as the pandemic progressed, the need arose to assess neutralization against different variants. In our stud(ies), we evaluated not only the Wuhan strain but also 25 distinct variants of concern (VoCs) and/or variants of interest (VoIs). For VoCs and VoIs, expressing results as "change in neutralization capacity expressed as a percentage (%)" is more effective as it illustrates the impact of mutations on neutralization, thereby allowing cross-variant comparisons. This adjustment did not alter the suggested endpoint, as both reporting methods reflect the ability of patients' antibodies neutralizing capacities.	From Day 0 until Month 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Unsolicited AEs	Number of Participants with Unsolicited AEs until the end of trial	From Day 0 until Month 12
Number of Participants With Solicited AEs	Number of Participants with Solicited AEs for 7 days after study vaccination dose.	From Day 0 until Day 7
Number of Participants With Rate of SAEs Grade ≥3	Number of Participants with Rate of serious adverse events (SAEs) Grade ≥3 according to the National Cancer Institute Common Toxicity Criteria up to three months after study vaccination dose.	From Day 0 until Month 3
Change in Cellular Immune Response Measured by qPCR 14 Days After 4th Vaccination Dose	Change in cellular immune response (CD4+ and CD8+ T cell response) to SARS-CoV-2 measured by fold change of CXCL10 mRNA levels measured by qPCR after 4th vaccination dose, to be determined in a subgroup only.	From Day 0 until Day 14
Neutralizing Antibody Titre Against Newly Emerging Variants in Bio-banked Samples After Study Vaccination Dose	"Neutralizing antibody titre (Virus Neutralisation Assay)" against newly emerging variants in bio-banked samples after a 3rd (Part A) or 4th vaccination dose (Part B), to be determined in a subgroup only. Microneutralization assay results were proposed to be reported as "change in neutralizing antibody titre (Virus Neutralisation Assay)" in the trial protocol. However, as the pandemic progressed, the need arose to assess neutralization against different variants. In our stud(ies), we evaluated not only the Wuhan strain but also 25 distinct variants of concern (VoCs) and/or variants of interest (VoIs). For VoCs and VoIs, expressing results as "change in neutralization capacity expressed as a percentage (%)" is more effective as it illustrates the impact of mutations on neutralization, thereby allowing cross-variant comparisons. This adjustment did not alter the suggested endpoint, as both reporting methods reflect the ability of patients' antibodies neutralizing capacities.	From Day 0 until Month 12

Collaborators and Investigators

• Sponsor: Oliver Cornely, MD
• Collaborators: European Commission; VACCELERATE
• Investigators: Principal Investigator: Oliver A Cornely, MD, University of Cologne

Publications and helpful links

General Publications

• Neuhann JM, Stemler J, Carcas A, Frias-Iniesta J, Bethe U, Heringer S, Tischmann L, Zarrouk M, Cuppers A, Konig F, Posch M, Cornely OA. 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. Trials. 2022 Oct 8;23(1):865. doi: 10.1186/s13063-022-06791-y.

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2021
• Primary Completion (Actual): October 1, 2022
• Study Completion (Actual): September 13, 2023

Study Registration Dates

• First Submitted: November 11, 2021
• First Submitted That Met QC Criteria: December 14, 2021
• First Posted (Actual): December 16, 2021

Study Record Updates

• Last Update Posted (Estimated): May 20, 2025
• Last Update Submitted That Met QC Criteria: May 2, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Elderly; Booster; COVID-19; Immunogenicity; Vaccination; BNT162b2; mRNA-1273; head-to-head comparison
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19
• Other Study ID Numbers: EU-COVAT-1_AGED; 2021-004526-29 (EudraCT Number); uni-koeln-4602 (Other Identifier: University of Cologne)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Making de-identified/anonymized data accessible is currently under way. We expect to grant access through a central independent data repository no later than January 2025. Any pertinent information will be updated in due course.
• IPD Sharing Time Frame: Making de-identified/anonymized data accessible is currently under way. We expect to grant access through a central independent data repository no later than January 2025. Any pertinent information will be updated in due course.
• IPD Sharing Access Criteria: To be announced.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No