E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of COVID-19 infection |
Prevención de la infección por COVID-19 |
|
E.1.1.1 | Medical condition in easily understood language |
Prevention of COVID-19 infection |
Prevención de la infección por COVID-19 |
|
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 reactogenicity between treatment arms after a 4th vaccination dose against SARS-CoV-2. |
Comparar la reactogenicidad entre los brazos de tratamiento después de administrar la 4ª dosis de la vacuna contra el SARS-CoV-2. |
|
E.2.2 | Secondary objectives of the trial |
• To compare the immunogenicity against wild-type SARS-CoV-2 between treatment arms after a 4th vaccination dose against SARS-CoV-2. • To evaluate descriptively the immunogenicity 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. |
Comparar la inmunogenicidad contra el SARS-CoV-2 de tipo salvaje entre los brazos de tratamiento tras la administración de una 4ª dosis de la vacuna frente al SARS-CoV-2.
Evaluar descriptivamente la inmunogenicidad frente a las variantes de SARS-CoV-2 entre los brazos de tratamiento después de una cuarta dosis de vacunación contra el SARS-CoV-2.
Evaluar descriptivamente la respuesta inmune humoral a largo plazo (reactogenicidad e inmunogenicidad) de la 4ª dosis de vacunación frente al 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. |
Población de edad avanzada (≥75 años).
Para entrar en la parte B del estudio, el sujeto vacunado mediante una de las siguientes pautas de vacunación antes de entrar al estudio: 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
La última dosis debe haber sido recibida al menos 1 mes antes de entrar en el estudio. El estado de vacunación debe documentarse en el documento fuente y en el eCRD
El sujeto no puede presentar contraindicaciones a ninguna de las vaucnas que se van a administrar en el estudio
Firma voluntaria del consentimiento informado |
|
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. |
Paciente vacunado con un esquema de vacunación no contemplado en los criterios de inclusión
Última dosis de la vacuna recibida hace menos de un mes de la entrada en el estudio
Paciente vacunado frente a otra enfermedad en las 2 últimas semanas previas a la entrada en el estudio. La única vacuna que se permite haber recibido es la vacuna contra la gripe
Paciente recibiendo terapia inmunosupresora, por ejemplo paciente que está en continuo tratamiento con glucocorticosteroides recibiendo una dosis equivalente a >10 mg/día de prednisolona
Sujeto que está participando o ha participado en la parte A de este ensayo clínico |
|
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. |
Tasa de aumento de los títulos de anticuerpos en el doble de la cantidad inicial tras la 4ª dosis de la vacuna, medido mediante un ensayo inmunoabsorbente ligado a enzima cuantitativo (Anti-RBD-ELISA) contra la cepa inicial del virus, 14 días después de la 4ª dosis |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
14 days after IMP administration |
14 días tras la administración del IMP |
|
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 performed 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 performed 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. • Neutralizing antibody titre (Virus Neutralisation Assay) against variants of concern at 12 months after a 4th vaccination dose.
Exploratory endpoints: • Change in cellular immune response measured by qPCR 14 days after 4th booster dose in a subgroup analysis. • Neutralising capacity measured by neutralising activity against newly emerging variants in bio-banked samples in a subgroup analysis after a 4th vaccination dose. • Correlates of humoral immune response, cellular immune responses and viral neutralising capacity against SARS-CoV-2 variants of concern (VOCs). |
Variables de seguridad: Acontecimientos adversos no solicitados hasta el final del estudio
Acontecimientos adversos solicitados durante los 7 primeros días tras haber recibido la 4ª dosis
Tasa de acontecimientos adversos graves (AAG) de grado ≥3 según los Criterios Comunes de Toxicidad del Instituto Nacional de Cáncer ocurridos hasta tres meses después de la administración de la 4ª dosis de la vacuna
Variables secundarias: Cambio en el título de anticuerpos neutralizantes (ensayo de neutralización del virus) contra la cepa inicial del virus 14 días después de haber recibido una 4ª dosis de la vacuna en un subgrupo de sujetos.
Cambio en el título de anticuerpos neutralizantes (ensayo de neutralización del virus) frente a variantes de interés en un subgrupo de pacientes, 14 días después de haber recibido la 4ª dosis de la vacuna.
Nivel del título de anticuerpos a los 12 meses después de haber recibido una 4º dosis de la vacuna medido medicante un ensayo cuantitativo inmunoabsorbente ligado a enzimas (ensayo anti-RBD-ELISA).
Título de anticuerpos neutralizantes (ensayo de neutralización del virus) frente al tipo salvaje SARS-CoV-2 a los 12 meses de haber recibido una 4ª dosis de la vacuna.
Título de anticuerpos neutralizantes (ensayo de neutralización del virus) frente a las distintas variantes de interés del SARS-CoV-2 12 meses después de haber recibido una 4ª dosis de vacunación.
Variables exploratorias: Cambio en la respuesta inmune celular (respuesta celular CD4+ y CD8+ T) medida por qPCR 14 días despuésde la 4ª dosis en un análisis de subgrupos.
Título de anticuerpos neutralizantes (ensayo de neutralización del virus) frente a variantes emergentes de SARS-CoV-2 encontradas en muestras de biobanco después de haber recibido la 4ª dosis en un análisis de subgrupos.
Correlación entre la respuesta inmune humoral, la respuesta inmune celular y la capacidad de neutralización viral contra las variantes de interés (COV) del SARS-CoV-2. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
at 7 days, 14 days and/or 12 months after IMP administration |
a los 7 días, 14 días y/o 12 meses después de la administración de IMP |
|
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 |
Immunogenicity |
Inmunogenicidad |
|
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
Germany |
Ireland |
Lithuania |
Norway |
Spain |
Sweden |
Switzerland |
|
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
|
day of database lock |
El día del cierre de la base de datos |
|
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 | 21 |