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

Sponsor

Oliver Cornely, MD (Other)

Overall Status

Recruiting

CT.gov ID

NCT05160766

Collaborator

European Commission (Other), VACCELERATE (Other)

550

Enrollment

Location

Arms

17.7

Anticipated Duration (Months)

31.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 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 elderly, a usually neglected population. Additional vaccines and extended follow-up visits can be added through amendments of this sub-protocol. As stated in the EU-COVAT master protocol, this trial, i.e., the EU-COVAT-1_AGED study, implements a specific safety monitoring strategy (see below).

Cohorts and arms can be withdrawn or added as deemed necessary according to the criteria specified in this protocol

Condition or Disease	Intervention/Treatment	Phase
Vaccination Reaction COVID-19 Vaccination; Infection	Biological: Comirnaty(BTN162b2) Biological: Spikevax (mRNA-1273)	Phase 2

Detailed Description

PLEASE NOTE:

This protocol refers to Part B of the clinical trial in which new accruals are randomized to a 4th vaccination (second booster) with either BNT162b2 or mRNA-1273. Part A of the present trial in which individuals received a 3rd vaccination (first booster) is closed to further recruitment as of January 13, 2022. With the massive roll-out of booster campaigns throughout Europe, Part A was abandoned because of a poor recruitment rate. Individuals in Part A are followed-up as specified in protocol version V04_0 and analyzed descriptively, the statistical analysis plan will be adapted accordingly.

Randomisation in Part B Subjects who - prior to study entry - got a primary vaccination series and 3rd vaccination dose 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

will receive a 4th vaccination dose with an allocation ratio of 1:1 to either BNT162b2 or mRNA-1273. Accordingly, there are 6 cohorts/arms (equalling 12 intervention arms). All individuals who were randomized to BNT162b2 represent Group 1, all individuals who were randomized to mRNA-1273 represent Group 2.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

550 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a randomised controlled, adaptive, multicentre Phase II Part B protocol evaluating different booster strategies in individuals aged 75 years and older already vaccinated against SARS-CoV-2. This trial foresees testing of different vaccines as a fourth vaccine dose ( second booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 and SARS-CoV-2 variants in the elderly.This is a randomised controlled, adaptive, multicentre Phase II Part B protocol evaluating different booster strategies in individuals aged 75 years and older already vaccinated against SARS-CoV-2. This trial foresees testing of different vaccines as a fourth vaccine dose ( second booster) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 and SARS-CoV-2 variants in the elderly.

Masking:

None (Open Label)

Masking Description:

No blinding is foreseen in this trial

Primary Purpose:

Prevention

Official Title:

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)

Actual Study Start Date :

Nov 8, 2021

Anticipated Primary Completion Date :

Apr 1, 2022

Anticipated Study Completion Date :

May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Comirnaty-Comirnaty-Comirnaty Participants are already fully vaccinated with 3x Comirnaty (BNT162b2) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial.	Biological: Comirnaty(BTN162b2) Single booster shot (4th dose) of already approved BioNTech/ Pfizer vaccine that protect against COVID-19 infection Other Names: BioNTech/ Pfizer Biological: Spikevax (mRNA-1273) Single booster shot (4th dose) of already approved Moderna vaccine that protect against COVID-19 infection Other Names: Moderna
Active Comparator: Spikevax-Spikevax-Spikevax Participants are already fully vaccinated with 3x Spikevax (mRNA-1273) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial.	Biological: Comirnaty(BTN162b2) Single booster shot (4th dose) of already approved BioNTech/ Pfizer vaccine that protect against COVID-19 infection Other Names: BioNTech/ Pfizer Biological: Spikevax (mRNA-1273) Single booster shot (4th dose) of already approved Moderna vaccine that protect against COVID-19 infection Other Names: Moderna
Active Comparator: Vaxzevria-Vaxzevria-Spikevax Participants are already fully vaccinated with 2x Vaxzevria (ChAdOx-1-S) and 1x Spikevax (mRNA-1273) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial.	Biological: Comirnaty(BTN162b2) Single booster shot (4th dose) of already approved BioNTech/ Pfizer vaccine that protect against COVID-19 infection Other Names: BioNTech/ Pfizer Biological: Spikevax (mRNA-1273) Single booster shot (4th dose) of already approved Moderna vaccine that protect against COVID-19 infection Other Names: Moderna
Active Comparator: Vaxzevria-Vaxzevria-Comirnaty Participants are already fully vaccinated with 2x Vaxzevria (ChAdOx-1-S) and 1x Comirnaty (BNT162b2) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial.	Biological: Comirnaty(BTN162b2) Single booster shot (4th dose) of already approved BioNTech/ Pfizer vaccine that protect against COVID-19 infection Other Names: BioNTech/ Pfizer Biological: Spikevax (mRNA-1273) Single booster shot (4th dose) of already approved Moderna vaccine that protect against COVID-19 infection Other Names: Moderna
Active Comparator: Spikevax-Spikevax-Comirnaty Participants are already fully vaccinated with 2x Spikevax (mRNA-1273) and 1x Comirnaty (BNT162b2) when entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial.	Biological: Comirnaty(BTN162b2) Single booster shot (4th dose) of already approved BioNTech/ Pfizer vaccine that protect against COVID-19 infection Other Names: BioNTech/ Pfizer Biological: Spikevax (mRNA-1273) Single booster shot (4th dose) of already approved Moderna vaccine that protect against COVID-19 infection Other Names: Moderna
Active Comparator: Comirnaty-Comirnaty-Spikevax Participants are already fully vaccinated with 2x Comirnaty (BNT162b2) and 1x Spikevax (mRNA-1273) entering the trial, only the 4th dose will be administered in the study. Treatment will be given as a single shot of either Comirnaty (BTN162b2) or Spikevax (mRNA-1273) using the approved dose and mode of administration of each vaccine included in this trial.	Biological: Comirnaty(BTN162b2) Single booster shot (4th dose) of already approved BioNTech/ Pfizer vaccine that protect against COVID-19 infection Other Names: BioNTech/ Pfizer Biological: Spikevax (mRNA-1273) Single booster shot (4th dose) of already approved Moderna vaccine that protect against COVID-19 infection Other Names: Moderna

Outcome Measures

Primary Outcome Measures

Immunogenicity response to different mRNA-based vaccines as 4th vaccination dose [14 days after 4th dose]
Rate of 2-fold antibody titre increase following 4th dose vaccination with BNT162b2 (Comirnaty) and mRNA-1273 (Spikevax), measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wildtype virus at 14 days after 4th dose (versus immediately before vaccination).

Secondary Outcome Measures

Antibody titre level against wild-type SARS-CoV-2 after a 4th vaccination dose (second booster) [Up to 12 months after 4th dose]
Antibody titre level at 12 months after a 4th vaccination dose measured by a quantitative enzyme-linked immunosorbent assay (anti-RBD-ELISA assay).
Neutralizing antibody titre (Virus Neutralisation Assay) after a 4th vaccination dose [Up to 12 months after 4th dose]
Neutralizing antibody titre (Virus Neutralisation Assay) against wild-type SARS-CoV-2 at 12 months after a 4th vaccination dose
Neutralizing antibody titre (Virus Neutralisation Assay) after a 4th vaccination dose. [Up to 12 months after 4th dose]
Neutralizing antibody titre (Virus Neutralisation Assay) against variants of Concern (VOC) at 12 months after a 4th vaccination dose.
Change in neutralizing antibody titre (Virus Neutralisation Assay) after a 4th vaccination dose [14 days after 4th dose]
Change in neutralizing antibody titre (Virus Neutralisation Assay) against wild-type 14 days after a 4th vaccination dose, to be performed in a subgroup only.
Change in neutralizing antibody titre (Virus Neutralisation Assay) against variants of concern 14 days after a 4th vaccination dose, to be performed in a subgroup only. [14 days after 4th]
Change in neutralizing antibody titre (Virus Neutralisation Assay) against variants of concern 14 days after a 4th vaccination dose, to be performed in a subgroup only.

Other Outcome Measures

CD4+ and CD8+ T cell response following 4th vaccination dose (second booster) [14 days after 4th dose]
Change in cellular immune response (CD4+ and CD8+ T cell response) measured by qPCR 14 days after 4th booster dose in a subgroup analysis.
Neutralizing antibody titre (Virus Neutralisation Assay) against newly emerging Variants of Concern [Up to 12 months after 4th dose]
Neutralizing antibody titre (Virus Neutralisation Assay) against newly emerging variants in bio-banked samples in a subgroup analysis after 4th vaccination dose.
Correlates of immune response after 4th vaccination dose against SARS-CoV-2 Variants of Concern (VOC). [Up to 12 months after 4th dose]
Correlates of humoral immune response, cellular immune response and viral neutralising capacity against SARS-CoV-2 variants of concern (VOC).

Eligibility Criteria

Criteria

Ages Eligible for Study:

75 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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:

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.