Clinical trial NCT06189040: Immunogenicity After COVID-19 Vaccines in Adapted Schedules
Official title: Assessment of the Immunogenicity and Safety of Marketed Vaccines for COVID-19 After Regular Schedule and Adapted Vaccine Schedules and Routes: BNT162b2, mRNA-1273 Vaccine and ChAdOx1-S [Recombinant]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronavirus Disease 2019
COVID-19
Lead sponsor: Universiteit Antwerpen
Sponsor class: OTHER
First posted: 2024-01-03
Enrollment: 580
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The goal of this clinical trial is to compare different Coronavirus Disease 2019 (COVID-19) vaccination schedules in healthy adults that have not yet been exposed to SARS-CoV-2, the virus causing COVID-19. The main questions it aims to answer are:

1. Is it possible to adapt COVID-19 vaccination schedules while maintaining an adequate humoral immune response?
2. Is it possible to adapt COVID-19 vaccination schedules while maintaining an acceptable safety profile?

Participants will be vaccinated twice with a COVID-19 vaccine (on day 0, and on day 28 or 84). After each vaccination, they will collect information about adverse events in a diary for 14 days. Information about the occurrence of events such as hospitalizations and infections with SARS-CoV-2 will be collected by the investigator for up to 364 days after the first vaccination. Blood samples will be taken on different timepoints and used to assess immunity against SARS-CoV-2.

Researchers will compare 8 vaccination schedules to see if the immune response and safety profile is similar. Each participant will receive 1 of the following 8 vaccine schedules:

* BNT162b2 (30µg) on day 0, followed by BNT162b2 (30µg) on day 28
* BNT162b2 (20µg) on day 0, followed by BNT162b2 (20µg) on day 28
* BNT162b2 (30µg) on day 0, followed by BNT162b2 (30µg) on day 84
* BNT162b2 (30µg) on day 0, followed by mRNA-1273 (100µg) on day 28
* BNT162b2 (30µg) on day 0, followed by ChAdOx1-S \[recombinant\] on day 28
* BNT162b2 (6µg, intradermal administration) on day 0, followed by BNT162b2 (6µg, intradermal administration) on day 28
* mRNA-1273 (100µg) on day 0, followed by mRNA-1273 (100µg) on day 28
* mRNA-1273 (50µg) on day 0, followed by mRNA-1273 (50µg) on day 28


Eligibility criteria: Inclusion Criteria:

1. Male, female, or X (non-binary gender) subjects, 18-55y inclusive on the day of signing of the ICF
2. Provision of signed and dated informed consent form
3. Available at all provided timepoints of the study and is not planning to move abroad for the whole duration of the study
4. In good general health as evidenced by medical history and/or physical examination or adults with pre-existing medical conditions who are in stable condition. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment.
5. Willing and able to comply with all study procedures
6. Participants born female must be either:

   * of childbearing potential and using effective contraception for at least 1 month prior to screening and agree to use such a method during study participation until 1 months following the last study dose administration.
   * of non-childbearing potential.

Exclusion Criteria:

1. Previous clinical or microbiological confirmed diagnosis of COVID-19.
2. Febrile illness within 72hours before first vaccination (this is a temporary exclusion criterion).
3. Unstable, severe, progressive disease in the past 3 months.
4. History of malignancy during the past 5 years.
5. History of severe adverse reaction associated and/or anaphylaxis with a vaccine.
6. Known allergic reactions of any severity to polyethylene glycol \[PEG\] or to polysorbate (due to potential cross-reactive hypersensitivity with the vaccine ingredient PEG).
7. Primary or secondary immunodeficiency disorders (e.g. immunosuppressive disease or therapy, human immunodeficiency virus (HIV) infection...).
8. Chronic administration (defined as more than 14 days in total) of immunosuppressant or other immune-modifying drugs during the period starting 6 months prior to the first vaccine dose. For corticosteroids, this will mean prednisone 20 mg/day, or equivalent. Inhaled, nasal, opthalmic and topical steroids are allowed.
9. Pregnancy or lactation.
10. History of drug or alcohol abuse.
11. Anything in the opinion of the investigator that would prevent volunteers from completing the study or put the volunteer at risk, including relevant psychiatric diagnosis.
12. Previous vaccination or planned to accept other vaccination during this study with any coronavirus vaccine outside this study.
13. Previous vaccination or planned to accept other vaccination during this study with any coronavirus vaccine outside this study, with the exception of a third COVID-19 vaccine during fall/winter '21-'22.
14. Receipt of blood/plasma products or immunoglobulin, from 60 days before study intervention administration or planned receipt throughout the study.
15. Participation in another clinical trial with an IMP or a new medical device within 28 days prior to study entry and/or during study participation.
16. Participant is an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as first degree family members and household members of the employees or the investigator, or an employee of the sponsor.

Primary outcomes:
measure: Geometric mean titre of antibodies binding to the Receptor Binding Domain of SARS-CoV-2 S protein of the ancestral D614 SARS-CoV-2 virus strain
timeFrame: 28 days after the administration of the second study vaccine
Secondary outcomes:
measure: Occurrence of solicited adverse events
timeFrame: within 5 days after the administration of each study vaccine
measure: Occurrence of unsolicited adverse events
timeFrame: within 14 days after the administration of each study vaccine
measure: Occurrence of medically attended adverse events, adverse of special interest and serious adverse events
timeFrame: through study completion (up to 1 year after the first study vaccination)
measure: Occurrence of absenteeism
timeFrame: within 5 days after the administration of each study vaccine
measure: Geometric mean titre of antibodies binding to the Receptor Binding Domain of SARS-CoV-2 S protein of the ancestral D614 SARS-CoV-2 virus strain
timeFrame: 28 days after the administration of the third COVID-19 vaccine
measure: Geometric mean titre of neutralizing antibodies to the ancestral D614 SARS-CoV-2 virus strain and variants of concern
timeFrame: 28 days after the administration of the second study vaccin
measure: Geometric mean titre of neutralizing antibodies to the ancestral D614 SARS-CoV-2 virus strain and variants of concern
timeFrame: 28 days after the administration of the third COVID-19 vaccine
Other outcomes:
measure: PCR-confirmed SARS-CoV-2 infection with COVID-19 symptoms (any severity)
timeFrame: through study completion (up to 1 year after the first study vaccination)
measure: PCR-confirmed SARS-CoV-2 infection with severe COVID-19 (hospitalization, death)
timeFrame: through study completion (up to 1 year after the first study vaccination)
Locations:
city: Edegem
country: Belgium
facility: Centre for the Evaluation of Vaccination (CEV)
state: Antwerp
city: Ghent
country: Belgium
facility: Centre for Vaccinology (CEVAC)
state: East Flanders
city: Antwerp
country: Belgium
facility: Institute of Tropical Medicine (ITM)
city: Brussels
country: Belgium
facility: Hôpital Erasme
Study officials:
affiliation: Centre for the Evaluation of Vaccination
name: Katie Steenackers, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for the Evaluation of Vaccination
name: Nikita Hanning, MD
role: PRINCIPAL_INVESTIGATOR
References: