| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Coronavirus disease-19 (COVID-19) |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective is:
-To assess non-inferiority of the humoral immune response against SARS-Cov-2 infection of different vaccines and adapted vaccine schedules in comparison with the reference schedules (‘group a’ of each brand) |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
1. Safety
- To evaluate safety and reactogenicity of all different vaccination schedules
2. Health Economics
- To assess the impact of all different vaccination schedules on productivity
3. Immunogenicity
- To assess non-inferiority of the humoral immune response against SARS-Cov-2 infection of different vaccines and adapted vaccine schedules in comparison with the reference schedule (group a of each brand)
- To analyse immunogenicity (T cell response) of all vaccine schedules ( in subset of participants)
- To analyse immunogenicity (B cell response) of all vaccine schedules (in subset of participants)
- To analyse biophysical characteristics (subclasses and glycosylation) of all vaccine schedules |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
No separate title / study is foreseen.
However the T cell and B cell response immunogenicity off all vaccines schedules will be determined based on blood sampling of only a subset ( 30 out of 60 participants in each treatment group).
- To analyse immunogenicity (T cell response) of all vaccine schedules (subset of participants)
- To analyse immunogenicity (B cell response) of all vaccine schedules (subset of participants) |
|
| E.3 | Principal 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. |
|
| E.4 | Principal 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. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint is:
- GMT of antibodies binding to the RBD of SARS-CoV-2 S protein, as determined by SARS-CoV-2 binding antibodies assay (ELISA) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
The timepoint of the primary endpoint is:
- 28 days post second study vaccine |
|
| E.5.2 | Secondary end point(s) |
The secondary endpoints are:
1. Safety
- Solicited local and systemic adverse events (AEs)
- Unsolicited AEs
- Medically attended AEs (MAAEs), AEs of special interest (AESIs) and serious AEs (SAEs)
2. Health Economics
- 2 questions about absenteeism
3. Immunogenicity
- GMT of antibodies binding to the RBD of SARS-CoV-2 S protein, as determined by SARS-CoV-2 binding antibodies assay (ELISA)
- GMT of antibodies binding to the RBD of SARS-CoV-2 S protein of variants, as determined by SARS-CoV-2 binding antibodies assay (ELISA)
- GMT of Neutralizing antibodies to Wuhan strain and variants, as determined by SARS-CoV-2 neutralization assay
- T cell response to relevant peptide pools of SARS-CoV-2 virus strain, as determined by intracellular cytokine staining and flow cytometry
- Memory B cell responses to S protein of Wuhan strain and variants, as determined by B cell Elispot assay
- Wuhan and variants SARS-CoV-2 spike (S) protein specific serum IgG glycosylation, as determined by affinity purification and capillary electrophoresis |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Safety
- Solicited AEs within 5 days after each vaccination
- Unsolicited AEs until 14 days after each vaccination
- MAAEs, AESIs and SAEs continuously throughout the study
2. Health Economics
- Within 5 days after each vaccination
3. Immunogenicity
- GMT of antibodies binding to the RBD of SARS-CoV-2 S protein 28d post 3rd COVID-19 vaccine
- GMT of antibodies binding to the RBD of SARS-CoV-2 S proteinat all timepoints
- GMT of nAbs at 28 days post last study vaccine
- T cell response at D0 (pre 1st vaccine) and 28d post 2nd study vaccine, D182 and 28days post 3 COVID-19 vaccine
- Memory B cell responses at 28d post 2nd study vaccine, D182 and 28days post 3 COVID-19 vaccine
- SARS-CoV-2 spike (S) protein specific serum IgG glycosylation at timepoints based on available results |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
Immunogenicity
Health Economics |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | Yes |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Non-inferiority design.Partially single blind, since some info can be deducted based on the schedule |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 8 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
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