E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophylaxis for influenza virus |
Profilaxis para el virus de la gripe |
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E.1.1.1 | Medical condition in easily understood language |
Flu virus |
Virus de la gripe |
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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 | 17.0 |
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 |
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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 relative efficacy of aQIV compared to comparator vaccine as determined by RT-PCR-confirmed influenza |
La eficacia relativa de aQIV en comparación con un comparador según venga por RT-PCR de gripe . |
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E.2.2 | Secondary objectives of the trial |
* The relative efficacy of aQIV compared to comparator as determined by the proportion of subjects with culture-confirmed influenza * The relative efficacy of aQIV compared to comparator as determined by RT-PCR-confirmed influenza in age subgroups, in children at risk of influenza, and in children depending on previous vaccination status * The early relative efficacy of aQIV compared to comparator as determined by RT-PCR-confirmed influenza To compare antibody * responses between aQIV and comparator (including assessment of non-inferiority and superiority) * To evaluate healthcare utilization and health economic outcomes * To evaluate safety and tolerability of each study vaccine |
La eficacia relativa de aQIV en comparación con un comparador según venga determinado por la proporción de sujetos con gripe confirmadas en cultivos. - La eficacia relativa de aQIV en comparación con un comparador según venga determinado gripe confirmada por la RT-PCR en subgrupos de edad, y en niños con riesgo de gripe y en niños dependiendo de su estado previo de vacunación. - La eficacia temprana de aQIV comparada con un comparador según venga determinado por por la proporción de sujetos con gripe confirmada por RT-PCR. - Comparar la respuesta de anticuerpos entre aQIV y un comparador (incluyendo evaluación de no-inferioridad y superioridad) - Se evaluará la utilización de recursos sanitarios y los resultados relativos a la economía de la salud. - Se evaluará la seguridad y tolerabilidad de cada vacuna en estudio. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
* Children, males and females, healthy or at high risk of complications from influenza, between ?6 months to <72 months of age * Documented consent provided by the subject's parent(s)/legal guardian(s) * Subjects and/or subject's parent(s)/legal guardian(s) able to comply with all study procedures. |
* Niños y niñas sanos o con alto riesgo de complicaciones derivadas de la gripe, de ? 6 meses hasta < 72 meses de edad. * Consentimiento documentado facilitado por el/los progenitor(es)/tutor(es) legal(es) del sujeto. * Sujetos y/o progenitor(es)/tutor(es) legal(es) del sujeto capaces de cumplir con todos los procedimientos del estudio. |
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E.4 | Principal exclusion criteria |
* Subjects with a history of allergy to vaccine components * Additional eligibility criteria may be discussed by contacting the site |
* Sujetos con una historia de alergia a los componentes de la vacuna. * Criterios de elegibilidad aditionales deberán ser discutidos contactando con el centro |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is on RT-PCR-confirmed influenza cases occurring at >21 days and ? 180 days after the last vaccination or until the end of the influenza season, whichever is longer. |
El objetivo principal serán casos de gripe confirmados por RT-PCR que tengan lugar > 21 días y ? 180 días después de la última vacunación o hasta que termine la temporada de gripe, optando siempre por el período más largo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Weekly from Day 1 up to 180 days after the last vaccination or until the end of influenza season, whichever is longer. |
Semanalmente desde el Dia 1 a los 180 días después de la última vacunación o hasta que termine la temporada de gripe, optando siempre por el período más largo. |
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E.5.2 | Secondary end point(s) |
*Secondary efficacy endpoint: Hazard ratios calculated 1.Occurrence of culture-confirmed influenza cases in all subjects occurring at >21 days and ? 180 days after the last vaccination or until the end of the influenza season, whichever is longer, 2.Early occurrence of RT-PCR-confirmed influenza cases in all subjects on first-occurrence of RT-PCR-confirmed influenza cases *Secondary Immunogenicity Endpoints The endpoints for immunogenicity measured in aQIV and comparator as determined by HI are as follows: 1.Geometric mean HI titer (GMT). 2.Geometric mean ratio (GMR) 3.Percentage of vaccine naïve and non-naïve subjects achieving seroconversion; 4.Percentage of subjects with HI titer ? 1:40 5.Percentage of subjects with higher HI titer thresholds * Other Endpoints (Health Economic Outcome): 1.Percentage of subjects with a medical visit for respiratory illness associated with RT-PCR-confirmed influenza 2.Number of employment days missed by parent(s)/guardian(s) of subjects with RT-PCR-confirmed influenza. 3.Number of days of daycare, school or preschool missed by subjects associated with RT-PCR-confirmed influenza * Safety Endpoints: 1.Percentage of subjects with solicited AEs. 2.Percentage of subjects with all unsolicited AEs. 3.Percentage of subjects with SAEs, AEs leading to withdrawal from the study or study vaccination, New Onset of Chronic Disease (NOCD), Adverse Events of Special Interest(AESI) and all medications associated. |
* Objetivo secundario de eficacia: Cociente de riesgos calculados 1.Ocurrencia de casos de gripe confirmada en cultivo en todos los sujetos que sucedan entre los días 21 y 180 después de la última vacunación o hasta que termine la temporada de gripe, optando siempre por el período más largo. 2.Ocurrencia temprana de casos de gripe dconfirmada por RT-PCR en todos los pacientes en casos de gripe confirmada de primera aparición por RT-PCR. *Objetivos secundarios de Inmunogenicidad Los objetivos para inmunogenicidad medidos en aQIV y el comparador según viene determinado por IH son los siguientes: 1. Titulo medio geométrico de IH (GMT) 2. Tasa media geométrica (GMR) 3. Porcentaje de vacunación de pacientes naïve y no-naïve que logran la seroconversión; 4.Porcentaje de sujetos con un título de IH ? 1:40 5.Porcentaje de sujetos con altos umbrales de títulos de IH *Otros objetivos ( resultados relativos a la economía de la salud ): 1.Porcentaje de pacientes con visitas médicas debidas a enfermedades respiratorias asociadas a gripe confirmada por RT-PCR. 2. Número de días de trabajo perdidos por el/los progenitor(es)/tutor(es) legal(es) de los sujetos con gripe confirmada por RT-PCR. 3. Número de días , colegio o preescolar perdidos por los sujetos asociados a gripe confirmada por RT-PCR. *Objetivos de seguridad: 1. Porcentaje de sujetos con EAs solicitados 2.Porcentaje de sujetos con todos los EAs no solicitados. 3.Porcentaje de pacientes con EASs, EAs que llevaron a la retirada del estudio o a la vacunación del estudio, Nuevo inicio de enfermedades crónicas(NOCD), Acontecimientos adversos de interes especial (AESI) y toda la medicación asociada. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Immunogenicity Endpoints: 1.vaccine naïve subjects: on Day 1, 29, 50 & 209, vaccine non-naïve subjects: on Day 1, 22 & 181 2.vaccine naïve subjects on Day 29/Day 1, D50/D1 & D209/D1, non-naïve: D22/D1 & D181/D1 3.vaccine naïve subjects: on Day 29 & 50, non-naïve subjects: on Day 22 4.vaccine naïve subjects on Day 29, 50 & 209, non-naïve: Day 22 & 181 5.vaccine naïve subjects on Day 29, 50 & 209, non-naïve: Day 22 & 181 Other Endpoints (Health Economic Outcome): 1.within a window of 14 days after ILI-onset 2.within a window of 14 days after ILI-onset 3.within a window of 14 days after ILI-onset Safety Endpoints: 1.for 7 days following each vaccination 2.vaccine-naïve subjects: from Day 1 to 50, non-naïve subjects from Day 1 to 22 3. 12 months after last vaccination |
Objetivos secundarios de Inmunogenicidad: 1.Vacuna de sujetos naïve: en el Dia 1, 29, 50 y 209, vacuna de sujetos no naïve: en Dia 1, 22 y 181 2. Vacuna de sujetos naïve en Dia29/Dia 1, D50/D1 y D209/D1, no naïve: D22/D1 y D181/D1 3.Vacuna de sujetos naïve: en el Dia 29 y 50, vacuna de sujetos no-naïve: en Dia 22 |
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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 -Health Economic Outcome |
-Inmunogenicidad -Resultados de la Economia de la Salud |
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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) | No |
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 |
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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 | 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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
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 |
Canada |
Finland |
Italy |
Mexico |
Philippines |
Poland |
Russian Federation |
Spain |
Taiwan |
Thailand |
United States |
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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
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Completion of testing of the biological samples, to be achieved no later than 8 months after collection of the last biological sample visit. Evaluation of the primary and/or secondary immunogenicity/efficacy objectives requires testing of biological samples from study subjects. The last samples for the analysis of such objectives will be taken up to 180 d after the last vaccination (V7: D181 for non-naïve subj. or V9: D209 for naïve) or until end of influenza season, whichever is longer. |
xxx |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |