| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy volunteers (Active immunization against measles, mumps and rubella diseases of healthy children in their second year of life). |
| Voluntarios sanos (inmunización activa de niños sanos frente al sarampión, la parotiditis y la rubéola en el 2º año de vida) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Measles, mumps and rubella diseases |
| Sarampión, parotiditis y rubeola |
|
| 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 | 15.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10028257 |
| E.1.2 | Term | Mumps |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.1 |
| E.1.2 | Level | SOC |
| E.1.2 | Classification code | 10021881 |
| E.1.2 | Term | Infections and infestations |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10039252 |
| E.1.2 | Term | Rubella |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 15.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10027011 |
| E.1.2 | Term | Measles |
| 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 |
?To demonstrate the consistency of three manufacturing lots of Inv_MMR vaccine in terms of seroresponse rates to measles, mumps and rubella viruses at Day 42.
?To demonstrate the consistency of three manufacturing lots of Inv_MMR vaccine in terms of geometric mean concentrations (GMCs) for antibodies to measles, mumps and rubella viruses at Day 42.
?To demonstrate the non-inferiority of Inv_MMR (for the three pooled lots) compared to Com_MMR (for the two pooled lots) vaccine in terms of seroresponse rates for measles, mumps and rubella viruses at Day 42.
?To demonstrate non-inferiority of Inv_MMR (for the three pooled lots) compared to Com_MMR (for the two pooled lots) vaccine in terms of GMCs for antibodies to measles, mumps and rubella viruses at Day 42.
?To demonstrate an acceptable immune response for Inv_MMR in terms of seroresponse rates for measles, mumps and rubella viruses at Day 42. |
| -Probar la consistencia 3 lotes de la vacuna Inv_MMR según tasas de respuesta serológica a los virus del sarampión, rubéola y parotiditis en día 42 -Probar la consistencia de 3 lotes de la vacuna Inv_MMR, segun las medias geométricas de las concentraciones (GMC) para los anticuerpos frente a los virus del sarampión, rubéola y parotiditis el día 42 -Probar la no inferioridad de Inv_MMR (para los 3 lotes combinados), en comparación con la vacuna Com_MMR (para los 2 lotes combinados), según tasas de respuesta serológica a los virus del sarampión, rubéola y parotiditis en día 42 -Probar la no inferioridad de la vacuna Inv_MMR (para los 3 lotes combinados) frente a la vacuna Com_MMR (para los 2 lotes combinados), a juzgar por las GMCs para los anticuerpos frente a los virus del sarampión, rubéola y parotiditis en día 42 - Probar una respuesta inmunitaria aceptable a Inv_MMR, a juzgar por las tasas de respuesta serológica a los virus del sarampión, rubéola y parotiditis en el día 42 |
|
| E.2.2 | Secondary objectives of the trial |
?To demonstrate non-inferiority of the pooled Inv_MMR groups compared to the pooled Com_MMR groups in terms of seroresponse rate and GMC for varicella zoster virus (VZV) Abs at D 42 (in US children).
?To demonstrate non-inferiority of the pooled Inv_MMR compared to pooled Com_MMR groups in terms of GMC for hepatitis A virus (HAV) Abs at D 42 (in US).
?To demonstrate non-inferiority of the pooled Inv_MMR compared to pooled Com_MMR in terms of Abs to S. pneumoniae (PS) (13 serotypes), at D 42 (in US).
?To assess immunogenicity of Havrix with respect to the seroresponse rates for HAV Abs in pooled Inv_MMR in contrast to pooled Com_MMR at D 42 (in US).
?To assess immunogenicity of Prevnar 13 with respect to anti-PS Ab concs ? the cut-offs of 0.05, 0.2, 0.5, and 1.0 µg/mL for Abs to PS in the Inv_MMR or the Com_MMR at D 42 (in US).
?To assess safety and reactogenicity of Inv_MMR and Com_MMR when co-administered with Varivax, Havrix (to all children) and Prevnar 13 (in US). |
| -Probar no inferioridad de los grupos Inv_MMR combinados, comparados con grupos Com_MMR combinados, según tasa de respuesta serológica y GMCs para los anticuerpos frente al virus de varicela zóster (VZV) el día 42 (niños reclutados en EEUU) -Probar no inferioridad de los grupos Inv_MMR combinados, comparados con los grupos Com_MMR combinados, a juzgar por GMCs para los anticuerpos frente al virus de hepatitis A (HAV) el día 42 (niños reclutados en EEUU) -Probar no inferioridad de los grupos Inv_MMR combinados, comparados con los grupos Com_MMR combinados, a juzgar por los anticuerpos frente a S. pneumoniae (PS) (13 serotipos) el día 42 (niños a los que se les administre Prevenar 13 en EEUU) -Evaluar la inmunogenicidad de Havrix según las tasas de respuesta serológica para los anticuerpos frente a HAV en los grupos Inv_MMR combinados, comparados con los grupos combinados de la vacuna Com_MMR, el día 42 (niños reclutados en EEUU) -Ver resto de objetivos secundarios en el protocolo |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
?Male or female child between 12 and 15 months of age at the time of vaccination.
?The investigator believes that the parent(s) or Legally Acceptable Representative(s) (LAR(s)) of the child, can, and will comply with the requirements of the protocol.
?Written informed consent obtained from the parent(s)/LAR(s) of the child.
?Child is in stable health as determined by investigator?s clinical examination and assessment of child?s medical history.
For US children only:
?Child that previously received a 3-dose series of Prevnar 13 only (i.e., no doses given as Prevnar/Prevenar), at least 60 days prior to study entry. |
| -Niños o niñas de entre 12 y 15 meses de edad en el momento de la vacunación. -Los padres/representantes legales aceptables (RLA) del niño pueden y desean cumplir los requisitos del protocolo a juicio del investigador. -Consentimiento informado y firmado por los padres/RLA del niño. -La salud del niño es estable, de acuerdo con la exploración clínica del investigador y la evaluación de la historia clínica del niño. Solo para niños de EE. UU.: -Niño o niña que hubiera recibido con anterioridad una serie de 3 dosis de Prevenar 13 exclusivamente (es decir, ninguna dosis se administró como Prevnar/Prevenar), al menos 60 días antes de la inclusión en el estudio. |
|
| E.4 | Principal exclusion criteria |
?Child in care.
?Use of any investigational or non-registered product other than the study vaccine(s) during the period starting 30 days before the day of study vaccination (i.e., 30 days prior to Day 0) or planned use during the entire study period.
?Concurrently participating in another clinical study, in which the child has been or will be exposed to an investigational or a non-investigational product.
?Chronic administration of immunosuppressants, or other immune-modifying drugs during the period starting 180 days prior to the first vaccine dose or any planned administration of immunosuppressive and immune-modifying drugs during the entire study.
-For corticosteroids, this will mean prednisone, ?0.5 mg/kg/day or equivalent.
-Inhaled and topical steroids are allowed.
?Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting 30 days prior to study vaccination at Visit 1 and ending at Visit 2. Please Note:
-Inactivated influenza (Flu) vaccine and Haemophilus influenzae type b conjugate vaccine (Hib) vaccines may be given at any time during the study, including the day of study vaccination (Flu and Hib vaccines must be administered at a different location than the study vaccine/s).
-Any age appropriate vaccine may be given starting at Visit 2 and anytime thereafter.
?Administration of immunoglobulins and/or any blood products during the period starting 180 days before entering the study or planned administration from the date of vaccination through the immunogenicity evaluation at Visit 2.
?History of measles, mumps, rubella, varicella/zoster and/or hepatitis A disease.
?Known exposure to measles, mumps, rubella and/or varicella/zoster during the period starting within 30 days prior to first study vaccination.
?Previous vaccination against measles, mumps, rubella, hepatitis A and/or varicella virus.
?Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
?A family history of congenital or hereditary immunodeficiency.
?History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, including hypersensitivity to neomycin, latex or gelatin.
?Blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems.
?Acute disease at the time of enrollment. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection without fever.
?Active untreated tuberculosis based on medical history.
?Any other condition which, in the opinion of the investigator, prevents the child from participating in the study.
For US children only:
?Child that previously received a vaccination with heptavalent Prevnar/Prevenar (prior vaccination should be with 3 doses of Prevnar 13 only).
?Child that previously received a fourth dose of any pneumococcal conjugate vaccine. |
| ?Niños en acogida ?Uso de un producto (medicamento o vacuna) en investigación o no registrado distinto de la o las vacunas del estudio desde 30 días antes de la vacunación del estudio (es decir, 30 días antes del Día 0) o uso previsto durante todo el período de estudio. ?Participación simultánea en otro estudio clínico, si el niño ha sido o será expuesto a un producto en investigación o de naturaleza no experimental (producto farmacéutico o sanitario). ?Administración crónica (definida como la que se extiende 14 días consecutivos ó más) de inmunosupresores u otros inmunomoduladores desde 180 días antes de la primera dosis de la vacuna ó administración programada de un inmunosupresor o un inmunomodulador durante todo el estudio. ?En el caso de los corticoides, esto significa la administración de prednisona en dosis de ? 0,5 mg/kg/día o equivalente. ?Se permite el uso inhalado y tópico de esteroides. ?Administración programada/administración de una vacuna no prevista en el protocolo del estudio desde 30 días antes de la vacunación del estudio en la visita 1 y hasta la visita 2. Recuerde por favor lo siguiente: ?La vacuna inactivada de la gripe (Flu) y la vacuna conjugada de Haemophilus influenzae de tipo b (Hib) se pueden administrar en cualquier momento del estudio, incluido el día de la vacunación del estudio (las vacunas antigripal y Hib se administrarán en un lugar distinto al de las vacunas del estudio). ?Cualquier vacuna adecuada para la edad se podrá administrar a partir de la visita 2 y en cualquier momento posterior. ?Administración de inmunoglobulinas y/o cualquier hemoderivado desde 180 días antes de iniciar el estudio o administración programada desde la fecha de vacunación hasta la evaluación de la inmunogenicidad en la visita 2. ?Antecedentes de sarampión, rubéola, parotiditis, varicela/zóster y/o hepatitis A. ?Exposición conocida al sarampión, rubéola, parotiditis y/o varicela/zóster desde 30 días antes de la primera vacunación del estudio. ?Vacunación previa frente al sarampión, rubéola, parotiditis, hepatitis A y/o varicela. ?Cualquier estado de inmunosupresión o inmunodeficiencia conocido o sospechado por la historia clínica y la exploración física (no se exigirá ninguna prueba de laboratorio). ?Antecedentes familiares de inmunodeficiencia congénita o hereditaria. ?Antecedentes de enfermedades o reacciones alérgicas que pudieran exacerbarse con algún componente de las vacunas, incluida la hipersensibilidad a la neomicina, el látex o la gelatina. ?Discrasia sanguíneas, leucemias, linfomas de cualquier tipo u otra neoplasia maligna de la médula ósea o del sistema linfático. ?Enfermedad aguda en el momento del reclutamiento. (La enfermedad aguda se define como la presencia de una enfermedad moderada o grave, acompañada, o no, de fiebre.) La fiebre se define como una temperatura ? 38,0°C/100,4 °F por cualquier vía adecuada para la edad. Todas las vacunas se podrán administrar a personas con enfermedades leves, del tipo de diarrea, infección respiratoria alta leve y afebril. ?Tuberculosis activa no tratada, según la historia clínica. ?Cualquier otro trastorno que, en opinión del investigador, impida al niño participar en el estudio. Solo para niños de EE. UU.: ?Niño o niña que hubiera recibido vacunación con Prevnar/Prevenar heptavalente (la vacunación previa debía haberse efectuado únicamente con 3 dosis de Prevenar 13). ?Niño o niña que hubieran recibido una cuarta dosis de cualquier vacuna antineumocócica conjugada |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Immunogenicity of the MMR vaccines in terms of antibody concentration.
?Seroresponse to measles, mumps and rubella viruses (by ELISA).
?Measles, mumps and rubella virus antibody concentrations. |
Inmunogenicidad de las vacunas SRP en términos de concentraciones de anticuerpos
-Respuesta serológica a los virus del sarampión, la rubéola y la parotiditis
-Concentraciones de los anticuerpos frente al virus del sarampión, la rubéola y la parotiditis |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Immunogenicity of the Varivax, Havrix and Prevnar 13 vaccines in a subset of children, in terms of antibody concentrations.
?Seroresponse to VZV.
?VZV antibody concentrations.
?HAV antibody concentrations.
?Seroresponse to HAV.
?Pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) antibody concentrations.
?Pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) antibody concentrations ?0.05 µg/mL, ?0.2 µg/mL, ?0.5 µg/mL and ?1.0 µg/mL. |
| Inmunogenicidad de las vacunas Varivax, Havrix y Prevenar 13 en un subgrupo de niños -Respuesta serológica a VZV -Concentración de anticuerpos frente a VZV. -Concentración de anticuerpos frente a HAV. -Respuesta serológica a HAV. -Concentración de anticuerpos frente a los serotipos neumocócicos (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F y 23F). -Concentraciones de anticuerpos frente a los serotipos neumocócicos (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F y 23F) ?0,05 µg/mL, ?0,2 µg/mL, ?0,5 µg/mL y ?1,0 µg/mL |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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, Prevention |
| Inmunogenicidad, prevención |
|
| 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 | Yes |
| E.8.1.5 | Parallel group | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 17 |
| 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 |
| Argentina |
| Estonia |
| Finland |
| Mexico |
| United States |
|
| 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
|
| LVLS |
| Ultimo sujeto, última visita |
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 26 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 26 |
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