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    Summary
    EudraCT Number:2012-001042-18
    Sponsor's Protocol Code Number:A3L40
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-12-22
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2012-001042-18
    A.3Full title of the trial
    Booster Effect and Safety of a DTaP-IPV-Hib Combined Vaccine, with or without Hep B, in Healthy Subjects 11 to 18 Months of Age Who Received a Hexavalent or Hexavalent/Pentavalent Combined Vaccine during the Primary Series.
    Efecto de recuerdo y seguridad de una vacuna combinada DTaP-IPV-Hib, con o sin vacunación contra Hep B, en sujetos sanos de 11 a 18 meses de edad que recibieron una vacuna combinada hexavalente o hexavalente/pentavalente durante la serie primaria
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    DTaP-IPV-Hib, with or without Hep B, booster vaccination in subjects aged 11 to 18 months previously vaccinated with a DTaP-IPV-Hib combination vaccine, with or without Hep B.
    Vacunación de recuerdo DTaP-IPV-Hib, con o sin vacunación contra Hep B, en sujetos de 11 a 18 meses de edad que recibieron previamente una vacuna combinada DTaP-IPV-Hib, con o sin vacunación contra Hep B
    A.4.1Sponsor's protocol code numberA3L40
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1122-2362
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/229/2013
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorSanofi Pasteur SA
    B.1.3.4CountryFrance
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportSanofi Pasteur SA
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSanofi-Aventis, S.A.
    B.5.2Functional name of contact pointUnidad Estudios Clínicos
    B.5.3 Address:
    B.5.3.1Street Addressc/ Josep Pla nº2, 5ª planta
    B.5.3.2Town/ cityBarcelona
    B.5.3.3Post code08290
    B.5.3.4CountrySpain
    B.5.4Telephone number93 485 94 00
    B.5.6E-mailES-unidadestudiosclinicos@sanofi.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Prevenar 13
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Inc.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePrevenar 13
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPIntramuscular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 1
    D.3.9.3Other descriptive namePNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 1 CONJUGATED TO CRM197
    D.3.9.4EV Substance CodeSUB28210
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.2
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 3
    D.3.9.3Other descriptive namePNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 3 CONJUGATED TO CRM197
    D.3.9.4EV Substance CodeSUB30926
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.2
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 4
    D.3.9.3Other descriptive namePNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 4 CONJUGATED TO CRM197
    D.3.9.4EV Substance CodeSUB25336
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.2
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 5
    D.3.9.3Other descriptive namePNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 5 CONJUGATED TO CRM197
    D.3.9.4EV Substance CodeSUB30927
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.2
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 6A
    D.3.9.3Other descriptive namePNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 6A CONJUGATED TO CRM197
    D.3.9.4EV Substance CodeSUB30928
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.2
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 6B
    D.3.9.3Other descriptive namePNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 6B CONJUGATED TO CRM197
    D.3.9.4EV Substance CodeSUB25356
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4.4
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 7F
    D.3.9.3Other descriptive namePNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 7F CONJUGATED TO CRM197
    D.3.9.4EV Substance CodeSUB30929
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.2
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 9V
    D.3.9.3Other descriptive namePNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 9V CONJUGATED TO CRM197
    D.3.9.4EV Substance CodeSUB25343
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.2
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 14
    D.3.9.3Other descriptive namePNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 14 CONJUGATED TO CRM197
    D.3.9.4EV Substance CodeSUB25341
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.2
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 18C
    D.3.9.3Other descriptive namePNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 18C CONJUGATED TO CRM197 CARRIER PROTEIN
    D.3.9.4EV Substance CodeSUB76887
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.2
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 19A
    D.3.9.3Other descriptive namePNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 19A CONJUGATED TO CRM197
    D.3.9.4EV Substance CodeSUB30930
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.2
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 19F
    D.3.9.3Other descriptive namePNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 19F CONJUGATED TO CRM197
    D.3.9.4EV Substance CodeSUB25337
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.2
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 23F
    D.3.9.3Other descriptive namePNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 23F CONJUGATED TO CRM197
    D.3.9.4EV Substance CodeSUB25368
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.2
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Pentavac
    D.2.1.1.2Name of the Marketing Authorisation holderSanofi Pasteur
    D.2.1.2Country which granted the Marketing AuthorisationSweden
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePentavac
    D.3.2Product code DTaP-IPV-Hib
    D.3.4Pharmaceutical form Powder and suspension for suspension for injection
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPIntramuscular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPurified Diphtheria Toxoid
    D.3.9.2Current sponsor codeD
    D.3.9.3Other descriptive nameDIPHTHERIA TOXOID
    D.3.9.4EV Substance CodeSUB12489MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU international unit(s)
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number30
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPurified Tetanus Toxoid
    D.3.9.2Current sponsor codeT
    D.3.9.3Other descriptive nameTETANUS TOXOID
    D.3.9.4EV Substance CodeSUB12608MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU international unit(s)
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number40
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPERTUSSIS TOXOID
    D.3.9.2Current sponsor codePT
    D.3.9.3Other descriptive namePERTUSSIS TOXOID
    D.3.9.4EV Substance CodeSUB14817MIG
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPERTUSSIS FILAMENTOUS HAEMAGGLUTININ
    D.3.9.2Current sponsor codeFHA
    D.3.9.3Other descriptive namePERTUSSIS FILAMENTOUS HAEMAGGLUTININ
    D.3.9.4EV Substance CodeSUB20298
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPOLIOVIRUS (INACTIVATED) TYPE 1
    D.3.9.2Current sponsor codeIPV
    D.3.9.3Other descriptive namePOLIOVIRUS (INACTIVATED) TYPE 1 (MAHONEY STRAIN) PRODUCED ON VERO CELLS
    D.3.9.4EV Substance CodeSUB25669
    D.3.10 Strength
    D.3.10.1Concentration unit DAgU D antigen unit(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPOLIOVIRUS (INACTIVATED) TYPE 2
    D.3.9.2Current sponsor codeIPV
    D.3.9.3Other descriptive namePOLIOVIRUS (INACTIVATED) TYPE 2 (MEF-1 STRAIN) PRODUCED ON VERO CELLS
    D.3.9.4EV Substance CodeSUB25670
    D.3.10 Strength
    D.3.10.1Concentration unit DAgU D antigen unit(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number8
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPOLIOVIRUS (INACTIVATED) TYPE 3
    D.3.9.2Current sponsor codeIPV
    D.3.9.3Other descriptive namePOLIOVIRUS (INACTIVATED) TYPE 3 (SAUKETT STRAIN) PRODUCED ON VERO CELLS
    D.3.9.4EV Substance CodeSUB25671
    D.3.10 Strength
    D.3.10.1Concentration unit DAgU D antigen unit(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number32
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNHaemophilus Influenzae type b conjugate
    D.3.9.3Other descriptive nameHAEMOPHILUS TYPE B POLYSACCHARIDE CONJUGATED TO TETANUS TOXOID
    D.3.9.4EV Substance CodeSUB25275
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Prevention of infections caused by Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertussis, poliovirus type 1, 2 and 3, prevention against invasive infections caused by Haemophilus influenzae type b and infection caused by hepatitis B virus
    Prevención de infecciones provocadas por Corynebacterium diphtheriae,
    Clostridium tetani, Bordetella pertussis, poliovirus tipo 1, 2 y 3;
    prevención de infecciones invasivas provocadas por Haemophilus
    influenzae tipo b e infección provocada por el virus de la hepatitis B.
    E.1.1.1Medical condition in easily understood language
    Active immunisation against diphtheriae, tetanus, pertussis, hepatitis B, poliomyelitis and invasive infections caused by Haemophilus influenzae type b
    Inmunización activa contra difteria, tétanos, tos ferina, hepatitis B, poliomielitis e infecciones invasivas provocadas por Haemophilus influenzae tipo b.
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level LLT
    E.1.2Classification code 10036897
    E.1.2Term Prophylactic vaccination
    E.1.2System Organ Class 10042613 - Surgical and medical procedures
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level HLGT
    E.1.2Classification code 10043413
    E.1.2Term Therapeutic procedures and supportive care NEC
    E.1.2System Organ Class 10042613 - Surgical and medical procedures
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10021430
    E.1.2Term Immunisation
    E.1.2System Organ Class 10042613 - Surgical and medical procedures
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level HLT
    E.1.2Classification code 10021431
    E.1.2Term Immunisations
    E.1.2System Organ Class 10042613 - Surgical and medical procedures
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Immunogenicity
    Groups 1 and 2
    ? Assess the antibody persistence of DTaP-IPV-HB-Hib or Infanrix hexa following a 3-dose primary series at 2, 3, and 4 months of age (MoA) before the administration of a booster dose of either vaccine
    ? Describe the immunogenicity and booster effect of the DTaP-IPV-HBHib
    or Infanrix hexa vaccine given as a booster dose at 11 to 15 MoA concomitantly with PCV13 (after a primary series with the same vaccine)
    ? To describe the immunogenicity of a booster dose of PCV13 given from
    11 to 15 MoA
    Group 3
    ? Assess the antibody persistence of all valences contained in the
    vaccines administered in a mixed schedule following a 3-dose primary series at 2, 4, and 6 MoA before the administration of a booster dose of Pentavac
    ? Describe the immunogenicity and booster effect of Pentavac given at 18 MoA after the administration of a mixed schedule primary series combining a hexavalent and a pentavalent vaccine

    To describe the safety profile for group 1, 2 and 3
    Inmunogenicidad
    Grupos 1 y 2
    ?Evaluar la persistencia de anticuerpos de la vacuna DTaP-IPV-HB-Hib o de Infanrix hexa después de una serie primaria de 3 dosis antes de la administración de una dosis de recuerdo
    ? Describir la inmunogenicidad y el efecto de recuerdo de la vacuna DTaP-IPV-HB-Hib o de Infanrix hexa administradas como dosis de recuerdo entre los 11 y los 15 meses de edad de forma concomitante con PCV13
    ? Describir la inmunogenicidad de una dosis de recuerdo de PCV13 administrada entre los 11 y los 15 meses de edad.
    Grupo 3
    ? Evaluar la persistencia de anticuerpos de todas las valencias siguiendo un calendario mixto después de una serie primaria de 3 dosis, antes de la administración de una dosis de recuerdo de Pentavac
    ? Describir la inmunogenicidad y el efecto de recuerdo de Pentavac administrada a los 18 meses de edad después de una serie primaria de calendario mixto que combina una vacuna hexavalente y una pentavalente
    Describir el perfil de seguridad
    E.2.2Secondary objectives of the trial
    Not applicable
    No se aplica
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    An individual must fulfill all of the following criteria in order to be eligible for trial enrollment:
    1) Infants/toddlers previously included in Study A3L39 who completed
    the 3- dose primary series vaccination according to protocol
    2) Groups 1 and 2 (Germany and the Czech Republic) aged 11 to 15 months on the day of the first study visit; Group 3 (Spain) aged 18 months on the day of the first study visit
    3) Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative (and by an independent witness if required by local regulations)
    4) Subject and parent/legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures
    5) Covered by health insurance, if applicable
    Un individuo debe cumplir todos los criterios siguientes para poder participar en el ensayo:
    1) Lactantes/niños pequeños incluidos previamente en el ensayo A3L39 que hayan completado la vacunación de la serie primaria de 3 dosis de acuerdo con el protocolo
    2) Grupos 1 y 2 (Alemania y República Checa) de 11 a 15 meses de edad al día de la primera visita del ensayo; grupo 3 (España) de 18 meses de edad al día de la primera visita del ensayo
    3) El formulario de consentimiento informado ha sido firmado y fechado por el padre/madre o por otro representante legal (y por un testigo independiente si así lo exige la normativa local).
    4) El sujeto y el padre/madre/representante legal tienen la posibilidad de asistir a todas las visitas programadas y de cumplir todos los procedimientos del ensayo.
    5) Cubierto por un seguro médico, si corresponde.
    E.4Principal exclusion criteria
    An individual fulfilling any of the following criteria is to be excluded from
    trial enrollment:
    1) Participation at the time of study enrollment (or 4 weeks preceding the booster vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure
    2) Receipt of any out-of-study vaccines within the 2-week period prior to Visit 01 and within the 4-week period following the receipt of study vaccines or until all Visit 02 study procedures have been completed
    3) Receipt of immune globulins, blood or blood-derived products in the last 3 months
    4) Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 3 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
    5) History of diphtheria, tetanus, pertussis, poliomyelitis, Hep B or Haemophilus influenzae type b and pneumococcal infections, confirmed either clinically, serologically, or microbiologically
    6) Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances
    7) Known thrombocytopenia, as reported by the parent/legally acceptable representative
    8) Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination
    9) Subjects in an emergency setting, or hospitalized involuntarily
    10) Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion
    11) Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature ? 38.0°C). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided.
    12) Identified as a natural or adopted child of the investigator or employee with direct involvement in the proposed study
    13) If any of the following events are known to have occurred in temporal relation to the receipt of a pertussis-containing vaccine, the decision to give further doses of pertussis-containing vaccines should be carefully considered:
    ? Encephalopathy
    ? Temperature of ? 40°C within 48 hours not due to another identifiable cause
    ? Collapse of shock-like state (hypotonic-hyporesponsive episode [HHE]) within 48 hours of vaccination
    ? Persistent, inconsolable crying lasting ? 3 hours, occurring within 48 hours if vaccination
    ? Convulsions with or without fever, occurring within 3 days of vaccination
    Un individuo que cumpla cualquiera de los siguientes criterios no podrá participar en el ensayo:
    1) Participación al momento de la inclusión en el ensayo (o 4 semanas antes de la vacunación de recuerdo) o participación planificada durante el período de este ensayo en otro ensayo clínico en el cual se investigue una vacuna, un medicamento, un dispositivo médico o un procedimiento médico.
    2) Administración de una vacuna ajena al ensayo en el período de 2 semanas anterior a la visita 01 y dentro del período de 4 semanas siguiente a la administración de las vacunas del ensayo, o hasta que se hayan completado todos los procedimientos del ensayo de la visita 02.
    3) Recepción de inmunoglobulinas, sangre o productos derivados de la sangre en los últimos 3 meses.
    4) Inmunodeficiencia congénita o adquirida, conocida o sospechada, o recepción de terapias inmunosupresoras, tales como quimioterapia o radioterapia anticancerosa, en los 3 meses anteriores, o terapia con corticoides sistémicos de largo plazo (prednisona o equivalente durante más de 2 semanas consecutivas en los últimos 3 meses).
    5) Antecedentes de infecciones por difteria, tétanos, tos ferina, poliomielitis, Hep B o Haemophilus influenzae tipo b y por neumococo, confirmadas de forma clínica, serológica o microbiológica.
    6) Hipersensibilidad sistémica conocida a cualquiera de los componentes de la vacuna, o antecedentes de reacciones a la/s vacuna/s utilizada/s en el ensayo o a una vacuna que contenga las mismas sustancias que pongan en peligro la vida.
    7) Trombocitopenia conocida, informada por el padre/madre/representante legal.
    8) Trastorno hemorrágico o recepción de anticoagulantes en las 3 semanas anteriores a la inclusión, por los que resulte contraindicada la vacunación intramuscular.
    9) Sujetos en situación de urgencia u hospitalizados involuntariamente.
    10) Enfermedad crónica que, en opinión del investigador, se encuentre en una etapa en la que pudiese interferir con la realización o la finalización del ensayo.
    11) Enfermedad aguda/infección moderada o grave (a criterio del investigador) el día de la vacunación o enfermedad febril (temperatura ?38,0 °C). No se debe incluir en el ensayo a un posible sujeto hasta que la afección se haya resuelto o el episodio febril haya cedido.
    12) Está identificado como hijo/a natural o adoptado/a del investigador o de un empleado con participación directa en el ensayo propuesto.
    13) Si se informa alguno de los acontecimientos siguientes asociados cronológicamente con la administración de una vacuna que contenga un componente pertúsico, deberá evaluarse cuidadosamente la decisión de administrar otras dosis de vacunas que contengan un componente pertúsico:
    ? encefalopatía;
    ? temperatura ? 40°C dentro de las 48 horas siguientes, no provocada por ninguna otra causa identificable;
    ? colapso o estado similar al shock (episodio hipotónico hiporreactivo [HHE]) dentro de las 48 horas siguientes a la vacunación;
    ? llanto persistente inconsolable que se extiende ?3 horas, dentro de las 48 horas siguientes a la vacunación,
    ? convulsiones con o sin fiebre dentro de los 3 días siguientes a la vacunación.
    E.5 End points
    E.5.1Primary end point(s)
    Immunogenicity
    Ab Persistence
    The following endpoints will be used to assess the Ab persistence (for all valences except PCV13 antigens) before the booster doses at Day 0 (D0) (Visit 1 [V01]) of the study vaccines:
    ? Ab concentrations/titers for each valence
    ? Ab concentrations/titers above a pre-determined cut-off:
    ? Anti-D Ab concentrations ? 0.01 IU/mL and ? 0.1 IU/mL
    ? Anti-T Ab concentrations ? 0.01 IU/mL and ? 0.1 IU/mL
    ? Anti-poliovirus 1, 2 and 3 titers ? 8 (1/dil)
    ? Anti-Hep B Ab concentrations ? 10 mIU/mL and ? 100 mIU/mL
    ? Anti-PRP Ab concentrations ? 0.15 ?g/mL and ? 1.0 ?g/mL
    ? Anti-PT and anti-FHA Ab concentrations ? Lower Limit Of Quantitation (LLOQ)
    Booster Effect:
    The following endpoints will be used to assess the booster response for all antigens at D30 (V02):
    ? Ab concentrations/titers for each valence (including PCV13 for Groups 1 and 2 only)
    ? Ab concentrations/titers levels higher than a pre-determined cut-off:
    ? Anti-D Ab concentrations ? 0.01 IU/mL, ? 0.1 IU/mL, and ? 1.0 IU/mL
    ? Anti-T Ab concentrations ? 0.01 IU/mL, ? 0.1 IU/mL, and ? 1.0 IU/mL
    ? Anti-poliovirus 1, 2 and 3 titers ? 8 (1/dil)
    ? Anti-Hep B Ab concentrations ? 10 mIU/mL and ? 100 mIU/mL (Groups 1 and 2 only)
    ? Anti-PRP Ab concentrations ? 0.15 ?g/mL and ? 1.0 ?g/mL
    ? Anti-pneumococcal serotype 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F concentrations ? 0.35 ?g/mL (Groups 1 and 2 only)
    ? Individual concentration/titer ratio for each valence (D30 [V02]/D0 [V01]), except for PCV13 antigens
    ? Seroconversion for pertussis Ab (anti-PT and anti-FHA) defined as:
    ? Anti-PT and anti-FHA ? 4-fold Ab titers increase from D0 (V01) to D30 (V02)
    ? Booster response to pertussis (PT and FHA) defined as:
    ? Subjects whose pre-vaccination Ab concentrations are less than the
    < LLOQ, will demonstrate the booster response if they have postvaccination
    levels ? 4 x LLOQ
    ? Subjects whose pre-vaccination Ab concentrations are ? LLOQ but < 4 x LLOQ, will demonstrate the booster response if they have a 4-fold response (i.e. post- / pre-vaccination ? 4)
    ? Subjects whose pre-vaccination Ab concentrations are ? 4 x LLOQ, will demonstrate the booster response if they have a 2-fold response
    (i.e. post- / pre-vaccination ? 2)
    Safety
    ? Occurrence of any unsolicited systemic adverse events (AEs) reported in the 30 minutes after booster vaccination
    ? Occurrence of solicited, i.e. pre-listed in the subject's diary and electronic case report form (eCRF), injection site and systemic reactions occurring up to 7 days after booster vaccination
    ? Occurrence of unsolicited (spontaneously reported) AEs up to 30 days after booster vaccination
    ? Occurrence of adverse events of special interest (AESIs) and SAEs, throughout the trial period
    ? Other endpoints recorded or derived will be described at the time of statistical analysis plan. Depending on the item, these could include: nature (MedDRA preferred term), time of onset, duration, number of days of occurrence, grade of severity, relationship to vaccine, action taken, whether the AE led to early termination from the study, seriousness, or outcome
    Inmunogenicidad
    Persistencia de Ac
    Se utilizarán los siguientes criterios de valoración para evaluar la persistencia de Ac (para todas las valencias salvo los antígenos de PCV13) antes de las dosis de recuerdo el día 0 (D0) (visita 1 [V01]) de las vacunas del ensayo:
    ? Concentraciones/títulos de Ac para cada valencia
    ? Concentraciones/títulos de Ac por encima de un valor de corte predeterminado:
    ? Concentraciones de Ac anti-D ? 0,01 UI/mL y ? 0,1 UI/mL
    ? Concentraciones de Ac anti-T ? 0,01 UI/mL y ? 0,1 UI/mL
    ? Títulos contra los virus de la polio tipo 1, 2 y 3 ? 8 (1/dil)
    ? Concentraciones de Ac anti-Hep B ? 10 mUI/mL y ? 100 mUI/mL
    ? Concentraciones de Ac anti-PRP ? 0,15 µg/mL y ? 1,0 µg/mL
    ? Concentraciones de Ac anti-PT y anti-FHA ? límite inferior de cuantificación (LLOQ)
    Efecto de recuerdo:
    Se utilizarán los siguientes criterios de valoración para evaluar las respuestas de recuerdo contra todos los antígenos en el D30 (V02):
    ? Concentraciones/títulos de Ac para cada valencia (incluida PCV13 en los grupos 1 y 2 solamente)
    ? Concentraciones/niveles de títulos de Ac superiores a un valor de corte predeterminado:
    ? Concentraciones de Ac anti-D ? 0,01 UI/mL, ? 0,1 UI/mL y ? 1,0 UI/mL
    ? Concentraciones de Ac anti-T ? 0,01 UI/mL, ? 0,1 UI/mL y ? 1,0 UI/mL
    ? Títulos contra los virus de la polio tipo 1, 2 y 3 ? 8 (1/dil)
    ? Concentraciones de Ac anti-Hep B ? 10 mUI/mL y ? 100 mUI/mL (solo los grupos 1 y 2)
    ? Concentraciones de Ac anti-PRP ? 0,15 µg/mL y ? 1,0 µg/mL
    ? Concentraciones contra los serotipos neumocócicos 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F y 23F ? 0,35 µg/mL (solo los grupos 1 y 2).
    ? Proporción de concentraciones/títulos individuales de cada valencia (D30 [V02]/D0 [V01]), salvo para los antígenos de PCV13.
    ? Seroconversión para Ac antipertúsicos (anti-PT y anti-FHA), definida como:
    ? incremento ? 4 veces en los títulos de Ac anti-PT y anti-FHA entre D0 (V01) y D30 (V02)
    ? Respuesta de recuerdo a la tos ferina (PT y FHA) definida de la siguiente manera:
    ? Los sujetos cuyas concentraciones de Ac previas a la vacunación son <LLOQ manifestarán la respuesta de recuerdo si presentan niveles posteriores a la vacunación ?4 veces el LLOQ.
    ? Los sujetos cuyas concentraciones de Ac previas a la vacunación son ?LLOQ pero <4 veces el LLOQ manifestarán la respuesta de recuerdo si presentan una respuesta 4 veces mayor (niveles posteriores/niveles previos a la vacunación ?4).
    ? Los sujetos cuyas concentraciones de Ac previas a la vacunación son ?4 veces el LLOQ manifestarán la respuesta de recuerdo si presentan una respuesta 2 veces mayor (niveles posteriores/niveles previos a la vacunación ?2).
    Seguridad
    ? Ocurrencia de cualquier acontecimiento adverso (AA) sistémico no solicitado informado en los 30 minutos siguientes a la vacunación de recuerdo.
    ? Ocurrencia de reacciones en el lugar de la inyección y sistémicas solicitadas, es decir, enumeradas en el diario del sujeto y en el cuaderno de recogida de datos electrónico (CRDe), que se produzcan hasta 7 días después de la vacunación de recuerdo.
    ? Ocurrencia de AA no solicitados (informados espontáneamente) hasta 30 días después de la vacunación de recuerdo.
    ? Ocurrencia de acontecimientos adversos de interés especial (AAIE) y de AAG, durante todo el período del ensayo.
    ? Otros criterios de valoración registrados o derivados se describirán en el momento de implementarse el plan de análisis estadístico. En función del elemento, podrían incluir: naturaleza (término preferido de MedDRA), momento de inicio, duración, número de días de ocurrencia, grado de intensidad, relación con la vacuna, acción tomada, si el AA ocasionó el abandono prematuro del ensayo, gravedad o resultado.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Blood sampling
    All subjects will provide a pre-vaccination blood sample at D0 (V01) and a post-vaccination sample at D30 (V02).
    Collection of safety data
    Subjects' parents/legal representatives will record information about solicited reactions in a diary card (DC) from Days 0-7 post-vaccination, and will record information about unsolicited AEs from Days 0-30.
    Solicited reactions will be collected for DTaP-IPV-HB-Hib, Infanrix hexa, Pentavac and PCV13 vaccines.
    The SAEs will be recorded throughout the trial period.
    Staff will contact subjects' parents/legal representative by telephone at 2-3 days and 8-10 days after vaccination to discuss any safety information.
    Staff will review the Days 0-30 safety data with subjects' parents/legal
    representatives at V02.
    Extracción de muestras de sangre
    Una muestra de sangre antes de la vacunación el D0 (V01) y una muestra después de la vacunación el D30 (V02).
    Recogida de datos de seguridad
    Los padres/representantes legales de los sujetos recogerán la información sobre las reacciones solicitadas en un diario (DC) entre los días 0-7 después de la vacunación y recogerán la información sobre los AA no solicitados entre los días 0-30. Las reacciones solicitadas se registrarán para todas las vacunas.
    Los AAG se registrarán durante todo el periodo de ensayo.
    Contacto por teléfono los días 2-3 y los días 8-10 después de la vacunación para comentar la información de seguridad y para recordarles que completen los datos de seguridad en el diario.
    Revisión de los datos de seguridad de los días 0-30 en la V02.
    E.5.2Secondary end point(s)
    Not applicable
    No se aplica
    E.5.2.1Timepoint(s) of evaluation of this end point
    Not applicable
    No se aplica
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    blind-observer (group 1 and group 2) and open-label (group 3)
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA42
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial 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 the trial = LVLS
    final del estudio = LVLS (última visita del último sujeto)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 795
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 795
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers Yes
    F.3.2Patients No
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Vulnerable pop (infants): ICF signed by the subject's the parent(s)/legal representative (and by an independent witness if required by local regulations)
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state265
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 795
    F.4.2.2In the whole clinical trial 795
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    Ninguno
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Center for Public Health Research (CSISP )
    G.4.3.4Network Country Spain
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-03-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-02-03
    P. End of Trial
    P.End of Trial StatusCompleted
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