Assessing Immune Response of Different COVID-19 Vaccines in Older Adults

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Cohorts and arms can be withdrawn or added as deemed necessary according to the criteria specified in this protocol

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.

Eligibility Criteria:
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.