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

COVID-19 Clinical Trial

— EU-COVAT-1  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05160766
• Other study ID #: EU-COVAT-1_AGED
• Secondary ID: 2021-004526-29un
• Status: Completed
• Phase: Phase 2
• Start date: November 8, 2021
• Est. completion date: September 13, 2023

Study information

• Verified date: November 2023
• Source: University of Cologne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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 Cohorts and arms can be withdrawn or added as deemed necessary according to the criteria specified in this protocol

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 323
• Est. completion date: September 13, 2023
• Est. primary completion date: October 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 75 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Vaccination Reaction
• Vaccination; Infection

Intervention

Biological:
• Comirnaty(BTN162b2)
Single booster shot (4th dose) of already approved BioNTech/ Pfizer vaccine that protect against COVID-19 infection
• Spikevax (mRNA-1273)
Single booster shot (4th dose) of already approved Moderna vaccine that protect against COVID-19 infection

Locations

Country	Name	City	State
Germany	University Hospital Cologne	Cologne
Germany	University Hospital Frankfurt	Frankfurt
Germany	Hannover Medical School Hospital	Hannover
Ireland	Cork University Hospital	Cork
Ireland	Mater Misericordiae University Hospital	Dublin
Ireland	Royal College of Surgeons in Ireland	Dublin
Ireland	St. James's Hospital	Dublin
Ireland	St. Vincent's University Hospital	Dublin
Lithuania	Inlita JSC	Vilnius
Lithuania	Vilnius University Hospital Santaros Klinikos	Vilnius
Norway	Helse Bergen HF, Haukeland University Hospital	Bergen
Spain	Hospital Universitari Germans Trias i Pujol	Badalona
Spain	Bellvitge University Hospital	Barcelona
Spain	Reina Sofia University Hospital	Córdoba
Spain	La Paz University Hospital	Madrid
Spain	Biodonostia Health Research Institute	San Sebastián

Sponsors (3)

Lead Sponsor	Collaborator
Oliver Cornely, MD	European Commission, VACCELERATE

Countries where clinical trial is conducted

Germany,  Ireland,  Lithuania,  Norway,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CD4+ and CD8+ T cell response following 4th vaccination dose	Change in cellular immune response (CD4+ and CD8+ T cell response) measured by qPCR 14 days after 4th vaccination dose, to be determined in a subgroup analysis.	14 days after 4th vaccination dose
Other	Neutralizing antibody titre (Virus Neutralisation Assay) against newly emerging variants in bio-banked samples after 4th vaccination dose.	Neutralizing antibody titre (Virus Neutralisation Assay) against newly emerging variants in bio-banked samples in a subgroup analysis after 4th vaccination dose.	Up to 12 months after 4th vaccination dose
Other	Correlates of humoral immune response, cellular immune response and viral neutralising capacity against SARS-CoV-2 variants of concern (VOC).	Correlates of humoral immune response, cellular immune response and viral neutralising capacity against SARS-CoV-2 variants of concern (VOC), to be determined in a subgroup only.	Up to 12 months after 4th vaccination dose
Primary	Antibody titre increase 14 days after 4th vaccination dose.	Rate of 2-fold antibody titre increase 14 days after 4th vaccination dose measured by qualitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wildtype virus.	14 days after 4th vaccination dose
Secondary	Antibody titre level against wild-type SARS-CoV-2 after a 4th vaccination dose	Antibody titre level at 12 months after a 4th vaccination dose measured by a quantitative enzyme-linked immunosorbent assay (anti-RBD-ELISA assay).	Up to 12 months after 4th vaccination dose
Secondary	Neutralizing antibody titre (Virus Neutralisation Assay) after a 4th vaccination dose.	Neutralizing antibody titre (Virus Neutralisation Assay) against wild-type 14 days after a 4th vaccination dose, to be determined in a subgroup only.	14 days after 4th vaccination dose
Secondary	Neutralizing antibody titre (Virus Neutralisation Assay) after a 4th vaccination dose.	Neutralizing antibody titre (Virus Neutralisation Assay) against variants of Concern (VOC) 14 days after a 4th vaccination dose, to be determined in a subgroup only.	14 days after 4th vaccination dose
Secondary	Neutralizing antibody titre (Virus Neutralisation Assay) after a 4th vaccination dose.	Neutralizing atibody titre (Virus Neutralisation Assay) against wild-type SARS-CoV-2 at 12 months after a 4th vaccination dose, to be determined in a subgroup only.	Up to 12 months after 4th vaccination dose
Secondary	Neutralizing antibody titre (Virus Neutralisation Assay) after a 4th vaccination dose.	Neutralizing atibody titre (Virus Neutralisation Assay) against variants of concern at 12 months after a 4th vaccination dose, to be determined in a subgroup only.	Up to 12 months after 4th vaccination dose