E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of COVID-19 infection |
|
E.1.1.1 | Medical condition in easily understood language |
Prevention of COVID-19 infection |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084464 |
E.1.2 | Term | COVID-19 immunization |
E.1.2 | System Organ Class | 100000004865 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084465 |
E.1.2 | Term | COVID-19 vaccination |
E.1.2 | System Organ Class | 100000004865 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 24.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10085559 |
E.1.2 | Term | Revaccination with different COVID-19 vaccine |
E.1.2 | System Organ Class | 100000004865 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084462 |
E.1.2 | Term | SARS-CoV-2 vaccination |
E.1.2 | System Organ Class | 100000004865 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084463 |
E.1.2 | Term | SARS-CoV-2 immunisation |
E.1.2 | System Organ Class | 100000004865 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084466 |
E.1.2 | Term | SARS-CoV-2 immunization |
E.1.2 | System Organ Class | 100000004865 |
|
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 |
To compare the immune response between treatment arms after a 4th vaccination dose against SARS-CoV-2. |
|
E.2.2 | Secondary objectives of the trial |
• To compare the humoral response against wild-type SARS-CoV-2 between treatment arms after a 4th vaccination dose against SARS-CoV-2. • To evaluate descriptively the humoral response against SARS-CoV-2 variants of concern between treatment arms after a 4th vaccination dose against SARS-CoV-2. • To evaluate descriptively the long-term humoral immune response (reactogenicity and immunogenicity) of 4th vaccination dose against SARS-CoV-2. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subject is ≥75 years old. • For study entry in Part B the subject was vaccinated with one of the following vaccination regimens (1st + 2nd + 3rd dose): o BNT162b2 + BNT162b2 + BNT162b2 o BNT162b2 + BNT162b2 + mRNA-1273 o mRNA-1273 + mRNA-1273 + mRNA-1273 o mRNA-1273 + mRNA-1273 + BNT162b2 o ChAdOx-1-S + ChAdOx-1-S + BNT162b2 o ChAdOx-1-S + ChAdOx-1-S + mRNA-1273
• The last dose of the above 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. • No contra-indication against any of the vaccine products in the trial. • Written informed consent from subject has been obtained.
|
|
E.4 | Principal exclusion criteria |
• Prior to study entry the subject got vaccinated with a regimen not included in the above list. • 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. • Current immunosuppressive therapy, for example continuous glucocorticosteroid treatment equivalent to >10 mg/day prednisolone. • Subject participates or participated in Part A of this trial.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Rate of 2-fold antibody titre increase 14 days after the 4th vaccination dose measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA) against wild-type virus. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
14 days after IMP administration |
|
E.5.2 | Secondary end point(s) |
Safety endpoint: • Unsolicited AEs until the end of trial. • Solicited AEs for 7 days after a 4th vaccination dose. • Rate of severe adverse events (AEs) Grade ≥3 according to the National Cancer Institute Common Toxicity Criteria up to three months after a 4th vaccination dose
Secondary endpoints: • Change in neutralizing antibody titre (Virus Neutralisation Assay) against wild-type 14 days after a 4th vaccination dose, to be determined in a subgroup only. • Change in neutralizing antibody titre (Virus Neutralisation Assay) against variants of concern 14 days after a 4th vaccination dose, to be determined in a subgroup only. • Antibody titre level 12 months after a 4th vaccination dose measured by a quantitative enzyme-linked immunosorbent assay (anti-RBD-ELISA assay). • Neutralizing antibody titre (Virus Neutralisation Assay) against wild-type SARS-CoV-2 at 12 months after a 4th vaccination dose, to be determined in a sub-group only. • Neutralizing antibody titre (Virus Neutralisation Assay) against variants of concern at 12 months after a 4th vaccination dose, to be determined in a subgroup only.
Exploratory endpoints: • Change in cellular immune response measured by qPCR 14 days after 4th booster dose, to be determined in a subgroup only. • Neutralising capacity measured by neutralising activity against newly emerging variants in bio-banked samples after a 4th vaccination dose, to be determined in a sub-group only. • Correlates of humoral immune response, cellular immune responses and viral neutralising capacity against SARS-CoV-2 variants of concern (VOCs), to be determined in a sub-group only. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
at 7 days, 14 days and/or 12 months after IMP administration |
|
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 | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 18 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Lithuania |
Spain |
Germany |
Ireland |
Norway |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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 | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |