Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   35898   clinical trials with a EudraCT protocol, of which   5892   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2013-002236-24
    Sponsor's Protocol Code Number:261302
    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:2014-01-16
    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 number2013-002236-24
    A.3Full title of the trial
    A Phase 3b Continuation study of the Safety and Efficacy of PEGylated
    Recombinant Factor VIII (PEG-rFVIII; BAX-855) in Prophylaxis of Bleeding in Previously Treated Patients with Severe Hemophilia A
    Estudio de continuación en fase 3b de la seguridad y eficacia del factor VIII recombinante PEGilado (FVIIIr-PEG; BAX 855) para la profilaxis de hemorragias en pacientes con hemofilia A severa previamente tratados
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of the Safety and Effectiveness of PEGylated Recombinant Factor VIII (BAX-855) Administered for Prevention of Bleeding in Previously Treated Patients with Severe Hemophilia A (a blood clotting disorder).
    Un estudio sobre la seguridad y efectividad del factor VIII recombinante PEGilado (FVIIIr-PEG; BAX 855) administrado para la prevencion de hemorragis en pacientes con hemofilia A severa previamente tratados (un trastorno en la coagulación de la sangre).
    A.3.2Name or abbreviated title of the trial where available
    PEGylated rFVIII (BAX-855) in Hemophilia A
    A.4.1Sponsor's protocol code number261302
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01945593
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/72/2013
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBaxter Innovations GmbH
    B.1.3.4CountryAustria
    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 supportBaxter Innovations GmbH
    B.4.2CountryAustria
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBaxter Innovations GmbH
    B.5.2Functional name of contact pointMichal Chotar
    B.5.3 Address:
    B.5.3.1Street AddressIndustriestrasse 67
    B.5.3.2Town/ cityVienna
    B.5.3.3Post codeA-1221
    B.5.3.4CountryAustria
    B.5.6E-mailmichal_chotar@baxter.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 No
    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 namePEGylated rFVIII
    D.3.2Product code BAX-855 500IU/vial
    D.3.4Pharmaceutical form Powder and solvent for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNot applicable
    D.3.9.2Current sponsor codeBAX-855
    D.3.9.3Other descriptive nameBAX-855 (PEGYLATED RFVIII)
    D.3.9.4EV Substance CodeSUB90763
    D.3.10 Strength
    D.3.10.1Concentration unit IU international unit(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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 Yes
    D.3.11.13.1Other medicinal product typeRecombinant product with covalently bound polyethyleneglycol.
    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 No
    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 namePEGylated rFVIII
    D.3.2Product code BAX-855 1000IU/vial
    D.3.4Pharmaceutical form Powder and solvent for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNot applicable
    D.3.9.2Current sponsor codeBAX-855
    D.3.9.3Other descriptive nameBAX-855 (PEGYLATED RFVIII)
    D.3.9.4EV Substance CodeSUB90763
    D.3.10 Strength
    D.3.10.1Concentration unit IU international unit(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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 Yes
    D.3.11.13.1Other medicinal product typeRecombinant product with covalently bound polyethyleneglycol.
    D.IMP: 3
    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 Advate 1000 IU powder and solvent for solution for injection
    D.2.1.1.2Name of the Marketing Authorisation holderBaxter AG
    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 nameAdvate
    D.3.2Product code rAHF-PFM
    D.3.4Pharmaceutical form Powder and solvent for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOCTOCOG ALFA
    D.3.9.1CAS number 139076-62-3
    D.3.9.4EV Substance CodeSUB16449MIG
    D.3.10 Strength
    D.3.10.1Concentration unit IU international unit(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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: 4
    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 No
    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 namePEGylated rFVIII
    D.3.2Product code BAX-855 250IU/vial
    D.3.4Pharmaceutical form Powder and solvent for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNot applicable
    D.3.9.2Current sponsor codeBAX-855
    D.3.9.3Other descriptive nameBAX-855 (PEGYLATED RFVIII)
    D.3.9.4EV Substance CodeSUB90763
    D.3.10 Strength
    D.3.10.1Concentration unit IU international unit(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number250
    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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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 Yes
    D.3.11.13.1Other medicinal product typeRecombinant product with covalently bound polyethyleneglycol.
    D.IMP: 5
    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 No
    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 namePEGylated rFVIII
    D.3.2Product code BAX-855 2000IU/vial
    D.3.4Pharmaceutical form Powder and solvent for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNot applicable
    D.3.9.2Current sponsor codeBAX-855
    D.3.9.3Other descriptive nameBAX-855 (PEGYLATED RFVIII)
    D.3.9.4EV Substance CodeSUB90763
    D.3.10 Strength
    D.3.10.1Concentration unit IU international unit(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2000
    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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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 Yes
    D.3.11.13.1Other medicinal product typeRecombinant product with covalently bound polyethyleneglycol.
    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
    Severe hemophilia A (FVIII <1%)
    Hemofilia A severa (FVIII < 1%)
    E.1.1.1Medical condition in easily understood language
    Hemophilia A
    Hemofilia A
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.1
    E.1.2Level LLT
    E.1.2Classification code 10060612
    E.1.2Term Hemophilia A
    E.1.2System Organ Class 100000004850
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The co-primary objectives of the study are:
    1. To determine the safety of BAX-855 based of FVIII inhibitory antibody development
    2. To determine the efficacy of BAX-855 based on ABR as determined by development of spontaneous bleeds (bleeds not associated with trauma).
    Los objetivos co-principales del estudio son:
    1. Determinar la seguridad de BAX 855 en función de la incidencia del desarrollo de anticuerpos inhibidores anti-FVIII
    2. Determinar la eficacia de BAX 855 en función de la tasa anual de hemorragias
    E.2.2Secondary objectives of the trial
    - To determine the total ABR (spontaneous and traumatic bleeds)
    - To determine the rate of success of BAX-855 for treatment of breakthrough bleeding episodes
    - To characterize the success of BAX-855 for treatment of bleeding episodes based on the number of BAX-855 infusions needed for the treatment and the length of intervals between bleeding episodes
    - To compare the total weight-adjusted consumption for prophylaxis and for the treatment of bleeding episodes
    - To assess Health-Related Quality of Life (HRQoL) over time for subjects receiving BAX-855.
    - To determine the safety of BAX-855, as assessed by occurrence of AEs and changes in vital signs and clinical laboratory parameters
    - To determine the immunogenicity of BAX-855
    - To assess patient satisfaction, patient activity levels, and health resource use over time for subjects receiving BAX-855
    -Determinar la TAH total (episodios hemorrágicos espontáneos y traumáticos).
    -Determinar la tasa de éxito de BAX 855 para el tratamiento de episodios hemorrágicos intraterapéuticos.
    -Caracterizar el éxito de BAX 855 para el tto de episodios hemorrágicos a través del número de infusiones de BAX 855 para el tratamiento y de la duración de los intervalos de tiempo entre episodios hemorrágicos.
    -Determinar el consumo total de BAX 855 ajustado por peso para la profilaxis y el tratamiento de episodios hemorrágicos.
    -Evaluar la calidad de vida relacionada con la salud (CVRS) con el tiempo en pacientes que reciben BAX 855.
    - Determinar la seguridad de BAX 855, evaluada mediante la aparición de AA y los cambios en las constantes vitales y en los parámetros analíticos.
    -Determinar la inmunogenia de BAX 855.
    -Para evaluar la satisfacción de los pacientes, los niveles de actividad del paciente, y el uso de los recursos de la salud a través del tiempo de los sujetos que recibieron BAX-855
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects from other BAX-855 studies can be provided with the continuation study informed consent form (ICF) prior to the end of study visit to review and consider participation in this continuation study. These subjects will complete any additional screening assessments within 2 weeks of the previous study?s end of study visit and will return to the study site within 6 weeks of the previous study end of study visit to confirm eligibility for this continuation study.
    BAX-855 naïve subjects who are ? 12 years of age can only be enrolled in this continuation study after enrollment in the phase 2/3 pivotal study is closed. BAX-855 naïve subjects who are < 12 years of age and in countries where the pediatric PTP study is being conducted can only be enrolled in this continuation study after enrollment in the pediatric PTP study is closed.
    Subjects who meet ALL of the following criteria are eligible for this study:
    1. Subject and/or legal representative has/have voluntarily provided signed informed consent.
    2. Subject is from 0 to 75 years of age at screening.
    3. Subject is male with severe hemophilia A (FVIII clotting activity < 1%) as confirmed by central laboratory at screening (after at least a 72-hour washout period) or a documented FVIII clotting activity <1% (confirmation is only required for BAX-855 naïve subjects).
    4. Subject has documented previous treatment with pd FVIII or rFVIII concentrates for ? 150 EDs.
    5. Subject is currently receiving prophylaxis or on-demand therapy with FVIII.
    6. Subject has a Karnofsky (see Section 20.3) or Lansky performance score of ? 60.
    7. Subject is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ? 200 cells/mm3, as confirmed by central laboratory at screening.
    8. Subject is hepatitis C virus negative (HCV-) by antibody or PCR testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis.
    9. Subject is willing and able to comply with the requirements of the protocol.
    Los pacientes sin tratamiento previo con BAX 855 de ? 12 años solo se pueden registrarse en este estudio de continuación después de que se haya cerrado el registro en el estudio fundamental en fase 2/3. Los pacientes sin tratamiento previo con BAX 855 y menores de 12 años de aquellos países en los que se esté realizando el estudio en PTP pediátricos solo se pueden inscribir en este estudio de continuación después de que se haya cerrado el registro en el estudio en PTP pediátricos.
    Los pacientes que cumplan TODOS los siguientes criterios son aptos para este estudio:
    1. El paciente y/o su representante legal han proporcionado voluntariamente el consentimiento informado firmado.
    2. El paciente tiene entre 0 y 75 años de edad en el momento de la selección.
    3. El paciente es un varón con hemofilia A severa (actividad coagulante del FVIII < 1%) confirmada por el laboratorio central en el momento de la selección después de un período de lavado de al menos 72 horas o una actividad coagulante del FVIII < 1% documentada (solo se exige confirmación en el caso de los pacientes sin tratamiento previo con BAX 855).
    4. El paciente ha documentado haber recibido previamente tratamiento con concentrados de FVIII derivado de plasma o FVIII recombinante durante ? 150 días de exposición (DE) .
    5. El paciente está recibiendo actualmente profilaxis o tratamiento a demanda con FVIII.
    6. El paciente tiene una puntuación del grado de actividad de Karnofsky (véase la sección 20.3) o de Lansky ? 60.
    7. El paciente es negativo para el virus de la inmunodeficiencia humana (VIH?); o es VIH+ con enfermedad estable y recuento de células CD4+ ? 200 células/mm3, confirmado por el laboratorio central en el momento de la selección.
    8. El paciente es negativo para el virus de la hepatitis C (VHC?) mediante el análisis de anticuerpos o mediante PCR (si es positivo, el título de anticuerpos será confirmado mediante PCR), confirmado por el laboratorio central en la selección; o VHC+ con hepatitis estable crónica.
    9. El paciente está dispuesto y es capaz de cumplir los requisitos del protocolo.
    E.4Principal exclusion criteria
    Subjects who meet ANY of the following criteria are not eligible for this study:
    1. Subject has detectable FVIII inhibitory antibodies (? 0.4 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
    2. Subject has history of FVIII inhibitory antibodies (? 0.4 BU using the Nijmegen modification of the Bethesda assay or ? 0.6 BU using the Bethesda assay) at any time prior to screening.
    3. Subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand?s disease).
    4. Subject has known hypersensitivity towards mouse or hamster proteins, PEG, or Tween 80.
    5. Subject has severe chronic hepatic dysfunction [eg, ? 5 times upper limit of normal alanine aminotransferase (ALT), as confirmed by central laboratory at screening, or documented at a local laboratory within 6 months prior to screening, or a documented INR > 1.5].
    6. Subject has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening, or documented at a local laboratory within 6 months prior to screening.
    7. Subject has current or recent (< 30 days) use of other PEGylated drugs prior to study participation or scheduled use of such drugs during study participation.
    8. Subject has participated in another clinical study involving an investigational product (IP) other than BAX-855 or device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
    9. Subject has medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance.
    10. Subject is a family member or employee of the investigator.
    Los pacientes que cumplan ALGUNO de los siguientes criterios no son aptos para este estudio:
    1. El paciente presenta anticuerpos inhibidores anti-FVIII detectables (? 0,4 UB usando la modificación de Nijmegen del ensayo Bethesda) confirmado por el laboratorio central en la selección.
    2. El paciente tiene antecedentes de anticuerpos inhibidores anti-FVIII (? 0,4 UB usando la modificación de Nijmegen del ensayo Bethesda o ? 0,6 UB usando el ensayo Bethesda) en cualquier momento antes de la selección.
    3. Al paciente se le ha diagnosticado un defecto hemostático hereditario o adquirido aparte de la hemofilia A (p. ej., defecto cualitativo de las plaquetas o enfermedad de von Willebrand).
    4. El paciente tiene hipersensibilidad conocida a proteínas de ratón o de hámster, al PEG o al Tween 80.
    5. El paciente tiene insuficiencia hepática crónica severa (p. ej., nivel de alanina aminotransferasa [ALT] ? 5 veces el límite superior de la normalidad, confirmado por el laboratorio central en la selección, o documentado en un laboratorio local en los 6 meses previos a la selección, o un INR > 1,5 documentado).
    6. El paciente presenta insuficiencia renal severa (creatinina sérica > 2,0 mg/dl) confirmado por el laboratorio central en la selección o documentado en un laboratorio local en los 6 meses previos a la selección.
    7. El paciente usa actualmente o ha usado recientemente (< 30 días) otros fármacos PEGilados antes de su participación en el estudio o está previsto que utilice dichos fármacos durante su participación en el estudio.
    8. El paciente ha participado en otro estudio clínico con un PEI distinto a BAX 855 o dispositivo en los 30 días previos a su inclusión en el estudio o está previsto que participe en otro estudio clínico con un PEI o dispositivo en investigación durante el desarrollo de este estudio.
    9. El paciente tiene una enfermedad médica, psiquiátrica o cognitiva o consume drogas/alcohol, lo que, en opinión del investigador, afectaría a la seguridad o cumplimiento terapéutico del paciente.
    10. El paciente es familiar o empleado del investigador.
    E.5 End points
    E.5.1Primary end point(s)
    Safety: Development of inhibitory antibodies to FVIII
    Efficacy: Spontaneous ABR
    Seguridad: desarrollo de anticuerpos inhibidores anti-FVIII.
    Eficacia: TAH espontáneas.
    E.5.1.1Timepoint(s) of evaluation of this end point
    6 to 36 months. All subjects will continue on study until a minimum of 100 EDs per subject have been achieved across all BAX-855 studies in which each subject participated. Following 100 EDs, subjects will be given the option to continue until the study is terminated.
    6 a 36 meses. Todos los pacientes continuarán en el estudio hasta que se haya alcanzado un mínimo de 100 DE por paciente entre todos los estudios de BAX 855 en los que cada paciente participe. Una vez transcurridos los 100 DE, a los pacientes se les dará la opción de continuar hasta que termine el estudio.
    E.5.2Secondary end point(s)
    Efficacy
    1. Total ABR (spontaneous and traumatic bleeds)
    2. Rate of success of BAX-855 for treatment of breakthrough bleeding episodes
    3. Number of BAX-855 infusions needed for the treatment of bleeding episodes
    4. Time intervals between bleeding episodes
    5. Weight-adjusted consumption of BAX-855
    Safety
    1. Occurrence of AEs and SAEs
    2. Changes in vital signs and clinical laboratory parameters (hematology, clinical chemistry and lipids)
    3. Immunogenicity
    a. Binding antibodies (IgG and IgM) to FVIII, BAX-855, and PEG
    b. Anti-CHO antibodies
    Patient Reported Outcomes (PROs)
    Changes from baseline in the following:
    1. Bleed and pain severity as measured using the Haemo-SYM questionnaire
    2. HRQoL as assessed using the SF-36 questionnaire
    Eficacia
    1. TAH total (episodios hemorrágicos espontáneos y traumáticos).
    2. Tasa de éxito de BAX 855 para el tratamiento de episodios hemorrágicos intraterapéuticos.
    3. Número de infusiones de BAX 855 necesariaspara tratar los episodios hemorrágicos.
    4. Intervalos de tiempo entre episodios hemorrágicos.
    5. Consumo de BAX 855 ajustado por peso.
    Seguridad
    1. Aparición de AA y AAG.
    2. Cambios en las constantes vitales y en los parámetros analíticos (hematología, bioquímica clínica y lípidos).
    PEGylated rFVIII (BAX 855) Page 6 of 81
    Clinical Study Protocol Identifier: 261302 2013 OCT 02
    BAXTER CONFIDENTIAL - RESTRICTED: DO NOT DISTRIBUTE WITHOUT PRIOR APPROVAL.
    3. Inmunogenia
    a. Anticuerpos de unión (IgG e IgM) frente a FVIII, BAX 855 y PEG.
    b. Anticuerpos anti-CHO.
    Resultados percibidos por el paciente (RPP)
    Cambios respecto al valor basal en los siguientes parámetros:
    1. Intensidad de las hemorragias y del dolor determinada mediante el cuestionario Haemo-SYM.
    2. CVRS evaluada mediante el cuestionario SF-36.
    E.5.2.1Timepoint(s) of evaluation of this end point
    All subjects will continue on study until a minimum of 100 EDs per subject have
    been achieved across all BAX-855 studies in which each subject participated.
    Todos los pacientes continuarán en el estudio hasta que se haya alcanzado un mínimo de 100 DE por paciente entre todos los estudios de BAX 855 en los que cada paciente participe.
    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 Yes
    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 No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA50
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Austria
    Belgium
    Bulgaria
    Canada
    Czech Republic
    Germany
    Hong Kong
    Israel
    Japan
    Korea, Republic of
    Lithuania
    Malaysia
    Netherlands
    Poland
    Romania
    Russian Federation
    Serbia
    Spain
    Sweden
    Switzerland
    Taiwan
    Thailand
    Ukraine
    United Kingdom
    United States
    E.8.7Trial 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
    Ultima visita del último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months36
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months36
    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: 120
    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: 2
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 58
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 60
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 78
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 2
    F.2 Gender
    F.2.1Female No
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 159
    F.4.2.2In the whole clinical trial 200
    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)
    Continue with the expected normal treatment for Hemophilia A
    Continuar con el tratamiento habitual previsto para la hemofilia A
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-01-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-01-14
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-03-02
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA