Clinical trial NCT05160766: Assessing Immune Response of Different COVID-19 Vaccines in Older Adults
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prevention of COVID-19
Keywords: SARS-CoV-2
COVID-19
Vaccination
Immunogenicity
BNT162b2
mRNA-1273
Booster
Elderly
head-to-head comparison
Lead sponsor: University of Cologne
Sponsor class: OTHER
Collaborators: name: VACCELERATE
name: European Commission
First posted: 2021-12-16
Enrollment: 323
Sex: ALL
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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. This trial foresees testing of different vaccines as a third (first booster, Part A) or fourth vaccine dose (second booster, Part B) for comparative assessment of their immunogenicity and safety against SARS-CoV-2 and SARS-CoV-2 variants in the elderly.
Primary purpose: PREVENTION

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 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Antibody Titre Increase 14 Days After Study Vaccination Dose.
timeFrame: From Day 0 until Day 14
Secondary outcomes:
measure: Change in Neutralizing Antibody Titre Against Wild-type 14 Days After Study Vaccination Dose
timeFrame: From Day 0 until Day 14
measure: Change in Neutralizing Antibody Titre Against Variants of Concern 14 Days After Study Vaccination Dose
timeFrame: From Day 0 until Day 14
measure: Antibody Titre Level at 12 Months After a Study Vaccination Dose
timeFrame: From Day 0 until Month 12
measure: Neutralizing Antibody Titre Against Wild-type at 12 Months After Study Vaccination Dose
timeFrame: From Day 0 until Month 12
measure: Neutralizing Antibody Titre Against Variants of Concern at 12 Months After Study Vaccination Dose
timeFrame: From Day 0 until Month 12
Other outcomes:
measure: Number of Participants With Unsolicited AEs
timeFrame: From Day 0 until Month 12
measure: Number of Participants With Solicited AEs
timeFrame: From Day 0 until Day 7
measure: Number of Participants With Rate of SAEs Grade ≥3
timeFrame: From Day 0 until Month 3
measure: Change in Cellular Immune Response Measured by qPCR 14 Days After 4th Vaccination Dose
timeFrame: From Day 0 until Day 14
measure: Neutralizing Antibody Titre Against Newly Emerging Variants in Bio-banked Samples After Study Vaccination Dose
timeFrame: From Day 0 until Month 12
Locations:
city: Cologne
country: Germany
facility: University Hospital Cologne
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt
city: Hannover
country: Germany
facility: Hannover Medical School Hospital
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
city: Bergen
country: Norway
facility: Helse Bergen HF, Haukeland University Hospital
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Córdoba
country: Spain
facility: Reina Sofia University Hospital
city: Madrid
country: Spain
facility: La Paz University Hospital
city: San Sebastián
country: Spain
facility: Biodonostia Health Research Institute
Study officials:
affiliation: University of Cologne
name: Oliver A Cornely, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.