| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Profylaxis for Influenza virus |
| Profilaxis para el virus influenza |
|
| E.1.1.1 | Medical condition in easily understood language |
| Flu virus |
| Virus de la gripe |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10022000 |
| E.1.2 | Term | Influenza |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 |
- Primary Efficacy Objective(s):
To demonstrate absolute vaccine efficacy of QIVc versus a non-influenza comparator determined by first occurrence RT-PCR or culture confirmed influenza, due to any influenza Type A and B strain in subjects </=3 years to <18 years of age.
In case of successful demonstration of the primary efficacy objective:
- Co-Primary Efficacy Objective(s):
To demonstrate absolute vaccine efficacy of QIVc versus a non-influenza comparator determined by first occurrence RT-PCR or culture confirmed influenza, due to any influenza Type A and B strain in subjects ≥2 years to <18 years of age. |
Objetivo principal de eficacia:
Demostrar la eficacia absoluta de la vacuna QIVc frente a un comparador no antigripal, en su determinación mediante la primera aparición de gripe confirmada por RT-PCR o por cultivo, debida a cualquier cepa de virus de la gripe de tipo A o B, en sujetos de edades comprendidas entre </=3 y <18 años.
En caso de que se demuestre con éxito (véase la sección 8.2) el objetivo principal de eficacia:
Objetivo coprincipal de eficacia:
Demostrar la eficacia absoluta de la vacuna QIVc frente a un comparador no antigripal, en su determinación mediante la primera aparición de gripe confirmada por RT-PCR o por cultivo, debida a cualquier cepa de virus de la gripe de tipo A o B, en sujetos de edades comprendidas entre ≥2 y <18 años |
|
| E.2.2 | Secondary objectives of the trial |
The following secondary objectives will be evaluated in specific age cohorts:
*Efficacy:
Demonstrate absolute vaccine efficacy of QIVc determined in 4 ways:
1. determined by first occurrence RT-PCR or culture confirmed influenza, due to any influenza Type A and B strain.
2. determined by first occurrence RT-PCR influenza, due to any influenza Type A and B strain.
3. determined by first occurrence culture confirmed influenza, due to any influenza Type A and B strain.
4. determined by first occurrence culture confirmed influenza, caused by influenza strains antigenically matched
- Exploratory: To further characterize the efficacy of QIVc, with specific attention for all-cause mortality, pneumonia and otitis media.
*Immunogenicity:
To characterize the immunogenicity of QIVc by HI assay.
- Exploratory: Further characterize the immune response, additional immunogenicity analyses may be conducted such as MN.
*Safety:
Assess the safety and tolerability of QIVc. |
Los siguientes objetivos secundarios serán evaluados en determinadas cohortes de edad:
-Eficacia:
Demostrar la eficacia absoluta de la vacuna QIVc frente a un comparador no antigripal, en su determinación mediante 4 maneras :
1.mediante la primera aparición de gripe confirmada por RT-PCR o por cultivo, debida a cualquier cepa de virus de la gripe de tipo A o B.
2.mediante la primera aparición de gripe confirmada por RT-PCR, debida a cualquier cepa de virus de la gripe de tipo A o B.
3.mediante la primera aparición de gripe confirmada por cultivo, debida a cualquier cepa de virus de la gripe de tipo A o B.
4.mediante la primera aparición de gripe confirmada por cultivo, causada por cepas gripales con correspondencia antigénica con las cepas elegidas para la vacuna estacional |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Males or females ≥2 years to <18 years of age on the day of first study vaccination;
2. Individual has and/or has (a) parent(s) or legal guardian(s) who has/have given informed consent/assent after the nature of the study has been explained in accordance with the practices described in protocol and according to local regulatory requirements;
3. If the individual is of an age where, according to local regulations, informed assent is required, that individual has provided assent to participate in the study.
4. Individual and individual’s parent or legal guardian can comply with study procedures and are available for follow-up;
5. Individual is in generally good health as per the Investigator’s medical judgement; |
1. Varones o mujeres >/= 2 años a >18 años de edad en el primer dia de la vacunación de estudio.
2. El individuo tiene y/o tiene padre (s) o tutor (s) legal, al que le ha sido entregado el consentimiento informado/asentimiento después de que la naturaleza del estudio , se ha explicado de acuerdo con las prácticas descritas en el protocolo y de acuerdo con los requisitos reglamentarios locales.
3. Si el individuo tiene una edad en la que, de acuerdo con las regulaciones locales, se requiere consentimiento informado, ese individuo ha dado su consentimiento para participar en el estudio.
4. El padre(s) o tutor legal de la persona y el individuo pueden cumplir con los procedimientos del estudio y están disponibles para su seguimiento.
5. El individuo está generalmente en buen estado de salud a juicio médico del Investigador |
|
| E.4 | Principal exclusion criteria |
1. Individual with clinical signs of and/or an oral temperature of ≥ 100.4 F (38.0 degrees Celsius) within three days prior to vaccination;
2. Individuals with a known history of any anaphylaxis, serious vaccine reactions or hypersensitivity to any of the vaccine components described in investigator brochure, or having any of the contraindications listed in the package insert of the comparator vaccine;
3. Individuals with history of Guillain-Barré syndrome or other demyelinating diseases such as encephalomyelitis and transverse myelitis;
4. Female subject “of childbearing potential”, sexually active, and not used any of the “acceptable contraceptive method” for at least 2 months prior to study entry and intend to use until the end of subject participation;
5. Individual is pregnant or breast feeding female;
6. Individual and/or individual’ parent/guardians who are not able to comprehend or follow all required study procedures for the whole period of the study;
7. Individual has received prior Meningococcal ACWY vaccination that conflicts with national recommendations or local practices for timing of primary or booster vaccination
8. Individual has received influenza vaccination or has had documented influenza disease in the last 6 months;
9. Known or suspected congenital or acquired immunodeficiency; or receipt immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or systemic corticosteroid therapy (prednisone or equivalent) at any dose for more than 2 consecutive weeks (14 days) within the past 3months. Topical, inhaled and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids is also permitted;
10. Administration of immunoglobulin and/or any blood products within the 3 months preceding vaccination, or planned administration during the study;
11. Individual has participated in any clinical trial with another investigational product 30 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study. Concomitant participation in an observational study (not involving drugs, vaccines, or medical devices) is acceptable;
12. Medical conditions or treatments contraindicating intramuscular vaccination due to increased risk of bleeding. These may include known bleeding disorders (such as thrombocytopenia), or treatment with anticoagulants (such as warfarin) in the 3 weeks preceding vaccination. However, antiplatelet agents such as low-dose aspirin, ticlopidine (Ticlid) and clopidogrel (Plavix) are permitted;
13. Evidence, or history (within the previous 12 months) of drug or alcohol abuse;
14. Study personnel or immediate family members (brother, sister, child, parent), the spouse of study personnel or individuals who are financially or emotionally dependent on study staff
15. Participation in this trial in a prior season, if applicable.
16. Any clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study |
1. Individuo con signos clínicos y / o una temperatura oral de ≥ 100.4 F (38.0 grados Celsius) dentro de los tres días previos a la vacunación;
2. Personas con antecedentes conocidos de anafilaxis, reacciones serias a la vacuna o hipersensibilidad a cualquiera de los componentes de la vacuna descritos en el manual del investigador, o que tengan alguna de las contraindicaciones enumeradas en el prospecto de la vacuna comparativa;
3. Individuos con antecedentes de síndrome de Guillain-Barré u otras enfermedades desmielinizantes tales como encefalomielitis y mielitis transversa
4. Sujeto femenino "en edad fértil", sexualmente activo, y que no ha utilizado ninguno de los "métodos anticonceptivos aceptables" durante al menos 2 meses previos de la entrada al estudio y tiene la intención de usarlos hasta el final de la participación del sujeto;
5. El individuo está embarazada o en periodo de lactancia.
6. Los padres/tutores del individuo que no son capaces de comprender o seguir todos los procedimientos de estudio requeridos durante todo el período del mismo;
7. El individuo ha recibido una vacuna Meningococcal ACWY anterior que está en conflicto con las recomendaciones nacionales o las prácticas locales para el momento de la vacunación primaria o de refuerzo
8. El individuo ha recibido la vacunación contra la gripe o ha tenido enfermedad de influenza documentada en los últimos 6 meses;
9. Conocimiento o sospecha de inmunodeficiencia congénita o adquirida; O de recibir terapia inmunosupresora, tal como quimioterapia anticancerosa o terapia de radiación, en los últimos 6 meses; O corticosteroides sistémicos (prednisona o equivalente) en cualquier dosis durante más de 2 semanas consecutivas (14 días) en los últimos 3 meses. Se permiten corticosteroides tópicos, inhalados e intranasales. También se permite el uso intermitente (una dosis en 30 días) de corticosteroides intraarticulares;
10. Administración de inmunoglobulina y / o de cualquier producto sanguíneo dentro de los 3 meses anteriores a la vacunación o está planeada su administración durante el estudio
11. El Individuo ha participado en algún ensayo clínico con otro producto de investigación 30 días antes de la primera visita del estudio o tiene intención de participar en otro estudio clínico en cualquier momento durante la realización de este estudio. La participación concomitante en un estudio observacional (que no implica medicamentos, vacunas o dispositivos médicos) es aceptable.
12. Condiciones médicas o tratamientos que contraindican la vacunación intramuscular debido al mayor riesgo de sangrado. Estos pueden incluir trastornos de sangrado conocidos (como trombocitopenia) o tratamiento con anticoagulantes (como warfarina) en las 3 semanas anteriores a la vacunación. Sin embargo, se permiten los fármacos antiplaquetarios como aspirina de dosis baja, ticlopidina (Ticlid) y clopidogrel (Plavix);
13. Evidencia o historial (dentro de los 12 meses anteriores) de abuso de drogas o alcohol;
14. El personal del estudio o los miembros de la familia inmediata (hermano, hermana, hijo, padre), el cónyuge del personal del estudio o las personas que dependen financieramente o emocionalmente del personal del estudio
15. Participación en este ensayo en una temporada previa, si corresponde.
16. Cualquier condición clínica que, en opinión del investigador, pueda interferir con los resultados del estudio o plantear un riesgo adicional al sujeto debido a la participación en eses previos a la vacunación, o administración planeada durante el estudio |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
- Primary Efficacy Endpoint(s)
The primary efficacy endpoint is the time from the last study vaccination to the onset of the first occurrence confirmed influenza by either RT-PCR-confirmed or culture-confirmed, due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, occurring >14 days after the last vaccination and until the end of the influenza season. |
- Objetivo (s) primario de eficacia.
El criterio de valoración de los objetivos principal de la eficacia es el tiempo transcurrido desde la última vacunación del estudio hasta la primera aparición de gripe confirmada por RT-PCR o por cultivo, debida a cualquier cepa de virus de la gripe de tipo A o B, con independencia de la correspondencia antigénica con las cepas seleccionadas para la vacuna estacional, y que tenga lugar >14 días después de la última vacunación y hasta el fin de la estación gripal. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| >14 days after the last vaccination and until the end of the influenza season. |
| >14 días después de la última vacunación y hasta el fin de la estación gripal. |
|
| E.5.2 | Secondary end point(s) |
- Secondary Safety Endpoint(s)
Safety will be assessed by calculating:
* The percentage of subjects with solicited local and systemic adverse events for 7 days following vaccination at Day 1 (“previously vaccinated” subjects) or Day1 and Day 29, (“not previously vaccinated” subjects) in the QIVc group and the non-influenza comparator vaccine group.
* The percentage of subjects with all unsolicited AEs will be assessed from Day 1 to Day 22 for “previously vaccinated” subjects or Day 1 to Day 50 for “not previously vaccinated” subjects in the QIVc group and in non-influenza comparator vaccine group.
* Percentage of subjects with SAEs, AEs leading to withdrawal from the study and NOCDs reported during the subject’s entire participation in the study, i.e. from Day 1 to Day 181 (for “previously vaccinated” subjects) or to Day 209 (for “not previously vaccinated” subjects), or until the end of influenza season, whichever is longer, and all medications associated with these events.
* Percentage of subjects with medically-attended adverse events within 30 days after of first occurrence RT-PCR confirmed ILI.
- Secondary Efficacy Endpoint(s)
* The efficacy endpoint for secondary objective 1 is the time from the last study vaccination to the onset of the first occurrence confirmed influenza by either RT-PCR confirmed or culture-confirmed, due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, occurring at >14 days after the last vaccination and until the end of the influenza season.
* The efficacy endpoint for secondary objective 2 is the time from the last study vaccination to the onset of the first-occurrence confirmed influenza by RT-PCR confirmed, due to any influenza Type A or B strain regardless of antigen match to the strains selected for the seasonal vaccine, (occurring at >14 days after the last vaccination and until the end of the influenza season).
* The efficacy endpoint for secondary objective 3 is time from the last study vaccination to the onset of the first-occurrence confirmed influenza by culture confirmed, due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, (occurring at >14 days after the last vaccination and until the end of the influenza season).
* The efficacy endpoint for secondary objective 4 is the time from the last study vaccination to the onset of the first-occurrence confirmed influenza by culture-confirmed, due to influenza Type A or B strain antigenic matched to the strains selected for the seasonal vaccine, (occurring at >14 days after the last vaccination and until the end of the influenza season).
- Secondary Immunogenicity Endpoints
The measures for assessing immunogenicity as determined by HI are as follows:
* HI Geometric mean titers (GMTs) on Day 1 (all subjects), Day 22 (all “previously vaccinated” subjects receiving a single vaccine dose) or Days 29 and 50 (all “not previously vaccinated” subjects receiving 2 doses) for all 4 influenza strains.
* Percentage of subjects achieving seroconversion (defined as: either a prevaccination HI titer < 1:10 and a post-vaccination HI titer ≥ 1:40 or a prevaccination HI titer ≥ 1:10 and a ≥ 4-fold increase in post-vaccination HI titer) on Day 22 (all “previously vaccinated” subjects receiving a single vaccine dose) or Days 29 and 50 (all “not previously vaccinated” subjects receiving 2 doses) for all 4 influenza strains.
* HI Geometric mean Ratio (GMR) of Day 22/Day 1 (all “previously vaccinated” subjects receiving a single vaccine dose) or Day 29/Day 1 and Day 50/Day 1 (all “not previously vaccinated” subjects receiving 2 doses) for all 4 influenza strains.
* Percentage of subjects with HI titer ≥ 1:40 on Day 22 (all “previously vaccinated” subjects receiving a single vaccine dose) or Days 29 and 50 (all “not previously vaccinated” subjects receiving 2 doses) for all 4 influenza strains. |
- Criterios secundarios de valoración de la seguridad:
-Porcentaje de sujetos con acontecimientos adversos de recogida solicitada, que se evaluarán durante los 7 días siguientes a la vacunación del Día 1 (sujetos "vacunados previamente") o de los Días 1 y 29 (sujetos "no vacunados previamente"), en el grupo de QIVc y en el grupo de la vacuna de comparación no antigripal.
-Porcentaje de sujetos con cualquier acontecimiento de recogida no solicitada en el diario (unsolicited AE), que se evaluarán desde el Día 1 hasta el Día 22 en los sujetos «vacunados previamente» o desde el Día 1 hasta el Día 50 en los sujetos "no vacunados previamente", en el grupo de QIVc y en el grupo de la vacuna de comparación no antigripal
Porcentaje de sujetos con acontecimientos adversos graves, acontecimientos adversos que lleven a la retirada de la vacuna y/o del estudio, enfermedad pseudogripal y enfermedades crónicas de reciente aparición comunicados durante toda la participación del sujeto en el estudio, es decir, desde el Día 1 hasta el Día 181 (sujetos "vacunados previamente") o hasta el Día 209 (sujetos "no vacunados previamente"), y todos los medicamentos asociados a estos acontecimientos
Porcentaje de sujetos con acontecimientos adversos que hayan requerido atención médica en el plazo de los 30 días siguientes a la primera aparición de enfermedad pseudogripal |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| See above for specific timepoints per endpoint |
| Ver más arriba para tiempos específicos por objectivo. |
|
| 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 | 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| Non-flu vaccine comparator and saline |
|
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| 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 |
| Australia |
| Estonia |
| Finland |
| Lithuania |
| Philippines |
| Poland |
| South Africa |
| Spain |
| Thailand |
|
| 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
|
| End of study is defined as the completion of the testing of such biological samples, to be achieved no later than 8 months after last subject last visit. |
|
| 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 | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
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