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    Summary
    EudraCT Number:2015-003290-15
    Sponsor's Protocol Code Number:GTI1503
    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:2016-02-22
    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 number2015-003290-15
    A.3Full title of the trial
    A Multi-Centre, Open-Label, Single Arm Trial to Evaluate Efficacy, Pharmacokinetics, and Safety and Tolerability of IGSC 20% in Subjects with Primary Immunodeficiency
    Ensayo multicéntrico, abierto y con un solo grupo para evaluar la eficacia, la farmacocinética, la seguridad y la tolerabilidad de IGSC al 20 % en sujetos con inmunodeficiencia primaria.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Multi-Centre, Open-Label, Single Arm Trial to Evaluate Efficacy, Pharmacokinetics, and Safety and Tolerability of IGSC 20% in Subjects with Primary Immunodeficiency
    Ensayo multicéntrico, abierto y con un solo grupo para evaluar la eficacia, la farmacocinética, la seguridad y la tolerabilidad de IGSC al 20 % en sujetos con inmunodeficiencia primaria.
    A.3.2Name or abbreviated title of the trial where available
    GTI1503
    A.4.1Sponsor's protocol code numberGTI1503
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGrifols Therapeutics Inc.
    B.1.3.4CountryUnited States
    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 supportGrifols Worldwide Operations Ltd
    B.4.2CountryIreland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGrifols Therapeutics Inc.
    B.5.2Functional name of contact pointElena Gomez
    B.5.3 Address:
    B.5.3.1Street Address79 TW Alexander Drive
    B.5.3.2Town/ cityResearch Triangle Park
    B.5.3.3Post codeNC 27709
    B.5.3.4CountryUnited States
    B.5.4Telephone number+34638187353
    B.5.5Fax number+19193166684
    B.5.6E-mailegomez@novellaclinical.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 nameImmune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%)
    D.3.2Product code IGSC 20%
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNImmune Globulin Subcutaneous (Human), 20%, Caprylate/Chromatography Purified
    D.3.9.2Current sponsor codeGRF6017
    D.3.10 Strength
    D.3.10.1Concentration unit % percent
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 Yes
    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
    Primary Immunodeficiency (PI) diseases
    Inmunodeficiencia primaria (IDP)
    E.1.1.1Medical condition in easily understood language
    Primary Immunodeficiency (PI) diseases
    Inmunodeficiencia primaria (IDP)
    E.1.1.2Therapeutic area Body processes [G] - Immune system processes [G12]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level PT
    E.1.2Classification code 10061598
    E.1.2Term Immunodeficiency
    E.1.2System Organ Class 10021428 - Immune system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10045792
    E.1.2Term Unspecified disorder of immune mechanism
    E.1.2System Organ Class 10021428 - Immune system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level PT
    E.1.2Classification code 10064859
    E.1.2Term Primary immunodeficiency syndrome
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this Phase 3 study is to evaluate whether weekly administered IGSC 20% over a one year period will achieve not more than 1 SBI per subject per year in PI subjects.
    El objetivo principal de este estudio de fase 3 es evaluar si con la administración semanal de IGSC al 20 % durante un año, se produce como máximo una infección bacteriana grave (IBG) por paciente y año en pacientes con inmunodeficiencia primaria (IDP).
    E.2.2Secondary objectives of the trial
    ? To determine if IGSC 20% replacement therapy maintains mean trough IgG levels that are comparable to the mean trough blood levels with previous IgG replacement regimen
    ? To evaluate trough levels of IgG subclasses
    ? To evaluate antibody levels for Streptococcus pneumoniae, Hemophilus influenzae, and Clostridium tetani
    ? To evaluate the PK profile in adult PI subjects at steady state (after approximately 4 months [16 weeks]) of weekly administration of IGSC 20%
    ? Trough measles antibody titers (functional assay) are an exploratory variable for informational purposes
    ? To evaluate validated infections documented by positive radiograph, fever (> 38°C oral or > 39°C rectal), culture, or diagnostic testing for microorganisms e.g., bacterial, viral, fungal, or protozoal pathogens
    ? To evaluate no. of days on antibiotics, no. hospitalizations and no. days work/school/activities missed due to infections
    ? To assess the safety and tolerability of IGSC 20%
    *Si el tto. restitutivo con IGSC20% mantiene una media de cc. mín de IgG comparable a lo observado con el tto. restitutivo con IgG previo
    *Concentraciones (CCs) mín. de las subclases de IgG
    *CCs de los anticuerpos frente a S. pneumoniae, H. influenzae y C. tetani
    *Perfil FC en pac. adultos con IDP en el est. de equilibrio (aprox. después de 4 meses [16 sem]) de la admin. semanal de IGSC20%
    *Título mín de anticuerpos frente al virus del sarampión (ensayo funcional) constituye una variable exploratoria con fines informativos
    *Nº de infecciones confirmadas y documentadas por radiografía concluyente, fiebre (>38°C oral o >39°C rectal), cultivo o pruebas diagnósticas para la detección de microorg. (ej. bacterias, virus o protozoos patógenos)
    *Nº de días en tto. con antibióticos, el Nº de hospitalizaciones debidas a infección y el Nº de días laborables/académicos/de actividades cotidianas perdidos debido a las infecciones
    *Seguridad y tolerabilidad de la administración de IGSC20%
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Adults and adolescents between the ages of 2 and 75 years (inclusive) at Screening.
    2. Documented and confirmed pre-existing diagnosis of PI with features of hypogammaglobulinemia requiring IgG replacement therapy including but not limited to the following: humoral-based immunodeficiency syndromes (e.g., X-linked agammaglobulinemia, common variable immunodeficiency), and combined immunodeficiency syndromes without lymphocytopenia (e.g., hyper immunoglobin [IgM] immunodeficiency syndrome). Please also refer to Exclusion Criteria.
    3. The subject has not had an SBI within the last 3 months prior to Screening and has no SBI up to the time of the Baseline Visit.
    Note: if an SBI occurs during the Screening/Previous Regimen Phase and prior to the first dose of Grifols IGSC 20%, the subject will be a Screen Failure
    4. Currently on IgG replacement therapy (stable regimen [dose and dosing interval] via IV or SC infusion) for ? 3 consecutive months. Subjects receiving IVIG prior to study must receive a dosage of at least 200 mg/kg per infusion.
    5. Documentation (within previous 3 months) of an IgG trough level of ? 500 mg/dL on current IgG replacement therapy regimen.
    6. Screening/pre-Baseline trough IgG levels must be ? 500 mg/dL.
    Note: If Screening and/or pre-Baseline trough levels are not above this threshold the subject will be a Screen Failure, but may be re-screened following dose adjustment of their original IgG replacement therapy regimen and maintaining stable dosing for a period of at least 3 consecutive months prior to Screening a second time.
    7. The medical records for all subjects should be available to document diagnosis, previous infections and treatment.
    8. The subject has signed an informed consent.
    Note: The subject must sign the informed consent form (ICF) if at least 18 years old; for children of younger age the subject?s parent or legal guardian must sign the ICF and if appropriate/applicable, the subject must sign a Child Assent form approved by the Institutional Review Board or Ethics Committee (IRB/EC) per their requirements
    1.Adultos y niños con edades entre los 2 y 75 años (ambos incluidos) en la selección
    2.Diagnóstico anterior de IDP documentado y confirmado, con signos de hipogammaglobulinemia que precisa tto. restitutivo con IgG y que presenta las características siguientes, entre otras: síndromes de inmunodeficiencia de tipo humoral (ej. agammaglobulinemia ligada al cromosoma X e inmunodeficiencia común variable) y síndromes de inmunodeficiencia combinada sin linfocitopenia (ej. síndrome de inmunodeficiencia con hiperinmunoglobulina M [IgM]). Véase también el apartado Criterios de exclusión
    3.El paciente no ha presentado una IBG en los 3 meses anteriores a la selección y no presenta ninguna IBG hasta el momento de la visita basal
    Nota: En caso de IBG durante la fase de selección o con la pauta previa y antes de admin. la 1ª dosis de IGSC 20% de Grifols, se considerará que el paciente no supera la selección
    4.Actualmente en tto. restitutivo con IgG (con una pauta posológica estable [dosis e intervalo de dosificación] por infusión IV o SC) durante ? 3 meses consecutivos. En los pacientes que reciben IGIV antes del estudio, la dosis deberá ser de al menos 200 mg/kg por infusión
    5.Comprobación (en los 3 meses anteriores) de una cc. mínima de IgG ?500 mg/dl durante la pauta terapéutica actual de restitución con IgG
    6.Las concentraciones mín. de IgG en la selección o antes del momento basal deberán ser ?500 mg/dl.
    Nota: Si las concentraciones mín. en la selección o antes del momento basal no superan este valor límite, se considerará que el paciente no supera la selección pero se podrá volver a seleccionar después de ajustar la dosis de su pauta terapéutica original de restitución con IgG y mantener estable la dosificación durante un periodo de al menos 3 meses consecutivos antes de la selección por 2ª vez
    7.Deberá disponerse de la historia clínica de todos los pacientes para verificar el diagnóstico así como las infecciones y los tratamientos previos
    8.El paciente ha firmado un consentimiento informado.
    Nota: El paciente debe firmar el formulario de consentimiento informado (FCI) si tiene como mínimo 18 años de edad; en el caso de los pacientes menores de edad, los padres o el tutor legal del paciente deberán firmar el FCI y si conviene o corresponde, el paciente deberá firmar un formulario de asentimiento infantil aprobado por el Comité Institucional de Revisión o el Comité de Ética de la Investigación (CEI) para cumplir con sus requisitos.
    E.4Principal exclusion criteria
    1. Clinical evidence of any significant acute or chronic disease that, in the opinion of the Investigator, may interfere with successful completion of the trial or place the subject at undue medical risk
    2. The subject has had a known serious adverse reaction to immunoglobulin or any severe anaphylactic reaction to blood or any blood-derived product
    3. The subject has a history of blistering skin disease, clinically significant thrombocytopenia, bleeding disorder, diffuse rash, recurrent skin infections, or other disorders where SC therapy would be contraindicated during the study
    4. The subject has isolated IgG subclass deficiency, isolated specific antibody deficiency disorder, or transient hypogammaglobulinemia of infancy.
    5. The subject has known selective immunoglobulin A (IgA) deficiency (with or without antibodies to IgA)
    6. Females of childbearing potential who are pregnant, have a positive pregnancy test at Screening (serum) or Baseline (urine) (human chorionic gonadotropin [HCG]-based assay), are breastfeeding, or unwilling to practice a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device [IUD] or intrauterine system [IUS], condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence) throughout the study
    7. The subject has significant proteinuria (dipstick proteinuria ? 3+, known urinary protein loss > 1 g/24 hours, or nephrotic syndrome), has a history of acute renal failure, has severe renal impairment (blood urea nitrogen [BUN] or creatinine more than 2.5 times the upper limit of normal [ULN]), and/or is on dialysis
    8. The subject has Screening Visit values of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels exceeding 2.5 times the ULN for the expected normal range for the testing laboratory.
    9. The subject has hemoglobin < 9 g/dL at Screening
    10. The subject has a known previous infection with or clinical signs and symptoms consistent with current hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
    11. The subject has a history of or current diagnosis of deep venous thrombosis or thromboembolism (e.g., myocardial infarction, cerebrovascular accident, or transient ischemic attack); history refers to an incident in the year prior to Screening or 2 episodes over lifetime
    12. The subject is currently receiving anti-coagulation therapy which would make SC administration inadvisable (vitamin K antagonists, nonvitamin K antagonist oral anticoagulants [e.g., dabigatran etexilate targeting Factor IIa, rivaroxaban, edoxaban, and apixaban targeting Factor Xa], parenteral anticoagulants [e.g., fondaparinux]).
    13. The subject currently has a known hyperviscosity syndrome
    14. The subject has an acquired medical condition that is known to cause secondary immune deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (absolute neutrophil count less than 1000/µL [1.0 x 109/L]), or HIV infection/acquired immune deficiency syndrome (AIDS).
    15. The subject is HIV positive by NAT based on a Screening blood sample. The subject may enter the Previous Regimen Phase while the Screening blood sample is being tested, but will be a Screen Failure and will not undergo Baseline assessments if the HIV result is positive.
    16. The subject (if < 18 years of age) has non-controlled arterial hypertension at a level of greater than or equal to the 90th percentile blood pressure (either systolic or diastolic) for their age and height (See Appendix 4) or the adult subject has non-controlled arterial hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg)
    17. The subject is receiving any of the following medications: (a) immunosuppressants including chemotherapeutic agents, (b) immunomodulators, (c) long-term systemic corticosteroids defined as daily dose > 1 mg of prednisone equivalent/kg/day for > 30 days.
    Note: Intermittent courses of corticosteroids of not more than 10 days would not exclude a subject. Inhaled or topical corticosteroids are allowed.
    18. The subject has known substance or prescription drug abuse.
    19. The subject has participated in another clinical trial within 30 days prior to Screening (observational studies without investigative treatments [non-interventional] are permitted) or has received any investigational blood product within the previous 3 months
    20. The subject/caregiver is unwilling to comply with any aspect of the protocol, including the home SC infusions, blood sampling, and completion of an SC infusion diary for the duration of the study
    21. Mentally challenged subjects who cannot give independent informed consent
    22. In the opinion of the Investigator the subject may have compliance problems with the protocol and the procedures of the protocol.
    1.Signos de cualquier enf. importante aguda o crónica que, en opinión del investigador, pueda influir en el cumplimiento satisfactorio del ensayo o situar al pac. en una situación de riesgo médico excesivo
    2.Ha presentado una reacción adversa grave ya descrita a una Ig o alguna reacción anafiláctica grave a la sangre o los hemoderivados
    3.Antecedentes de dermatosis vesicante, trombocitopenia clínicamente significativa, trastornos hemorrágicos, exantema difuso, infecciones cutáneas recurrentes u otros trastornos para los que el tratamiento SC estaría contraindicado durante el estudio
    4.Deficiencia aislada de una subclase de IgG, una deficiencia aislada de ciertos anticuerpos o una hipogammaglobulinemia transitoria de la infancia
    5.Deficiencia selectiva de IgA, con o sin anticuerpos frente a las IgA
    6.Mujeres con posibilidad de quedar embarazadas, con una prueba de embarazo positiva en la selección (en suero) o en el momento basal (orina) (utilizando el ensayo de la HCG), que están en periodo de lactancia materna o son reticentes a utilizar un método anticonceptivo muy eficaz (antic. hormonales implantables, inyectables u orales, colocación de un DIU o un sistema intrauterino [SIU], uso de preservativo o diafragma con espuma/gel/película/crema/óvulo vaginal espermicida, esterilización masculina o abstinencia real) durante todo el estudio.
    7.Proteinuria pronunciada (proteinuria con la tira reactiva ?3+, pérdida urinaria de proteína confirmada de > 1 g/24 horas o síndrome nefrótico), tiene antecedentes de insuficiencia renal aguda, presenta disfunción renal grave (urea o creatinina > 2,5 veces superiores al límite superior de normalidad [LSN]) o recibe diálisis.
    8.Presenta en la visita de selección valores de AST o ALT > a 2,5 veces el LSN del intervalo de valores previstos en las pruebas analíticas
    9.Cifras de hemoglobina <9 g/dl en la selección.
    10.Ha tenido una infección confirmada con o sin signos y síntomas indicativos de una infección actual por el virus de la hepatitis B (VHB) o C (VHC)
    11.Antecedentes o se encuentra en proceso de diagn. de una trombosis venosa profunda o tromboembolia (ej.infarto agudo de miocardio, enf. cerebrovascular aguda o accidente isquémico transitorio); la historia clínica hace referencia a un incidente ocurrido en el año anterior a la selección o a 2 episodios a lo largo de su vida
    12.En tto. con anticoagulantes por lo que se desaconsejaría la admin. SC (antagonistas de la vit. K, anticoagulantes orales distintos de los antagonistas de la vit. K [ej., dabigatrán etexilato que actúa sobre el factor IIa; rivaroxabán, edoxabán y apixabán que actúan sobre el factor Xa] o anticoagulantes parenterales [ej. fondaparinux])
    13.Actualmente con síndrome de hiperviscosidad confirmado
    14.Enferm. que causa inmunodeficiencia 2ª, ej.: leucemia linfocítica crónica, linfoma, mieloma múltiple, neutropenia crónica o recurrente (neutrófilos totales inferior a 1.000/µl [1,0 x 109/l]), infección VIH o SIDA
    15.Infectado por el VIH según se ha comprobado mediante la técnica NAT en una muestra de sangre extraída en la selección. El paciente podrá incluirse en la fase con la pauta previa mientras se esperan los resultados en la muestra de sangre extraída en la selección pero se considerará como un pac. que no supera la selección y no se le realizarán las evaluaciones correspondientes al momento basal si el resultado es VIH positivo.
    16.(si tiene <18 años) HTA no controlada con un valor >o igual al percentil 90 de la PA (ya sea sistólica o diastólica) correspondiente a su edad y estatura (véase el Anexo 4) o el paciente adulto presenta hipertensión arterial no controlada (PA sistólica >160 mm Hg y/o PA diastólica >100 mmHg)
    17.En tto. con alguno de los medic. que se enumeran a cont: a) inmunosupresores incluidos los antineoplásicos, b) inmunomoduladores y c) corticoesteroides sistémicos a largo plazo definido como una dosis diaria >1 mg de un equivalente de prednisona/kg/día durante más de 30 días
    Nota: Los ciclos intermitentes con corticoesteroides no > a los 10 días de duración no serán motivo de exclusión de un paciente. Se permite el uso de corticoesteroides adm. por inhalación o vía tópica
    18.Se ha confirmado que es toxicómano o consume de manera excesiva medicamentos psicoactivos con potencial adictivo
    19.Ha participado en otro ensayo clínico en los 30 días anteriores a la selección (se admite la participación en Est. de observación sin ttos. de investigación [es decir, no farmacológicos]) o ha recibido algún hemoderivado en los 3 meses anteriores
    20.El pac. o el cuidador no están dispuestos a cumplir con algún aspecto del protocolo, como las infusiones SC en el domicilio, la extracción de muestras de sangre y la cumplimentación del diario de infusiones SC durante el estudio.
    21.Problemas mentales que no pueden otorgar por sí mismos el consentimiento informado
    22.En opinión del Inv., el pac. puede presentar problemas de cumplimento del protocolo y de sus proc.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy variable is the number of SBIs. Also, the percentage of subjects with SBIs will be summarized.
    La variable principal de eficacia es el número de IBG. También se anlizará el porcentaje de sujetos con IBG.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Sampling will be taken throughout Previous Regimen Phase and Treatment Phases 1 and 2.
    Las muestras serán tomadas a lo largo de la Fase con la Pauta Previa y en las Etapas 1 y 2 de tratamiento.
    E.5.2Secondary end point(s)
    The secondary endpoint of this study is trough concentrations of total IgG of previous regimen during the Screening/Previous Regimen Phase and the IGSC 20% Treatment Stages. It is measured to determine if IGSC 20% replacement therapy maintains mean trough IgG levels that are comparable to the mean trough blood levels with the previous IgG replacement regimen.

    Additional PK parameters include average trough concentration of IgG subclasses (IgG1, IgG2, IgG3, and IgG4), and concentration of antibody levels to S. pneumoniae, H. influenzae, and C. tetani (tetanus). Trough measles antibody titers (functional assay) are an exploratory variable for informational purposes.
    For the adult (n~20) PK subset, serial samples will be collected immediately before and after SC#17 infusion at steady state. The PK profile will include total IgG concentrations at timepoints over a 7-day period. PK parameters including AUC0-7days, Cmax, and tmax will be determined by a noncompartmental model using WinNonlin.

    Other efficacy variables include rate of infection of any kind (serious and non-serious) including acute sinusitis, exacerbation of chronic sinusitis, acute otitis media, pneumonia, acute bronchitis, infectious diarrhea, etc., which will be recorded as an AE with the Investigator answering the following question affirmatively in the eCRF: ?Is this an infection? (verbatim term delineating nature of infection). Validated infections documented by positive radiograph, fever (> 38°C oral or > 39°C rectal), culture, or diagnostic testing for microorganisms e.g., bacterial, viral, fungal, or protozoal pathogens (for instance, rapid streptococcal antigen test) will be analyzed separately.
    In addition, details regarding infections will include antibiotic treatment (oral, parenteral, oral plus parenteral, prophylactic, and therapeutic), and hospitalizations due to infection. Days lost from work/school/daily activities due to infections and related treatment comprise additional variables.
    Concentraciones mínimas del conjunto de IgG con la pauta previa durante la fase de selección o con la pauta previa y en las etapas del tratamiento con IGSC al 20 %. Determinar si el tratamiento restitutivo con IGSC al 20 % mantiene una media de concentraciones mínimas de IgG comparable a lo observado con el tratamiento restitutivo con IgG previo.

    Parámetros FC adicionales incluyen concentraciones mínimas de las subclases de IgG (IgG1, IgG2, IgG3 e IgG4), y concentraciones de los anticuerpos frente a Streptococcus pneumoniae, Haemophilus influenzae y Clostridium tetani (tétanos). El título mínimo de anticuerpos frente al virus del sarampión (ensayo funcional) constituye una variable exploratoria con fines informativos.
    Para el subgrupo FC adulto (n~20), se extraerán muestras sucesivas justo antes y después de la infusión SC#17 en estado de equilibrio.
    El perfil FC incluirá concentraciones del conjunto de IgG durante un período de 7 días.
    Los parámetros FC incluidos los valores de AUC0-7días, Cmáx, y tmáx, se determinarán empleando un modelo no compartimental del programa informático WinNonlin.

    Otras variables de eficacia incluyen tasa de infección de cualquier tipo (grave o no grave) por ejemplo: sinusitis aguda, reagudización de una sinusitis crónica, otitis media aguda, neumonía, bronquitis aguda, diarrea infecciosa, etc, que se notificará como un AA junto con la respuesta afirmativa del investigador a la pregunta siguiente en el eCRF: "Se trata de una infección?" (expresión exacta para describir el tipo de infección). Número de infecciones confirmadas y documentadas mediante radiografía concluyente, fiebre (>38 °C oral o >39 °C rectal), cultivo o pruebas diagnósticas para la detección de microorganismos (por ej., bacterias, virus o protozoos patógenos [como la prueba rápida para detectar el antígeno estreptocócico]) se analizarán separadamente.
    Además, detalles en relación a infecciones incluirán tratamiento con antibióticos (vía oral, parenteral y oral más parenteral; con fines profilácticos y terapéuticos), y hospitalizaciones debidas a infección. Número de días laborables/académicos/de actividades cotidianas perdidos por paciente y año debido a las infecciones y su tratamiento constituyen variables adicionales.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Sampling will be taken throughout Previous Regimen Phase and Treatment Phases 1 and 2.
    Las muestras serán tomadas a lo largo de la Fase con la Pauta Previa y en las Etapas 1 y 2 de tratamiento.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    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 No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    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 Information not present in EudraCT
    E.8.2.4Number of treatment arms in the trial1
    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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA40
    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 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
    Last Patient Last Visit
    Última visita último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months3
    E.8.9.2In all countries concerned by the trial days0
    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: 20
    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) No
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 10
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 20
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    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 Yes
    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
    As there are paediatric subjects, in this study assent for this group would be obtained through their parents, legal guardians or representatives.
    Como en este estudio hay sujetos pediátricos, se obtendrá el asentimiento de este grupo a través de sus padres, tutores o representantes legales.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state11
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 60
    F.4.2.2In the whole clinical trial 60
    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)
    The final infusion of IGSC 20% will be SC#52. One week post last SC infusion a Final Visit will occur where the patient will be assessed for the final time.
    La infusión final de IGSC 20% será la SC#52. Una semana después de la última infusión SC tendrá lugar la Visita Final en la que el paciente será evaluado por última vez.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-04-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-04-04
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-05-15
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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