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    Summary
    EudraCT Number:2020-002437-15
    Sponsor's Protocol Code Number:BO42354
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-07-23
    Trial 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 number2020-002437-15
    A.3Full title of the trial
    A PHASE III, OPEN-LABEL, MULTICENTER, SINGLE-ARM STUDY EVALUATING THE EFFICACY AND SAFETY OF CROVALIMAB IN ADOLESCENT AND PEDIATRIC PATIENTS WITH ATYPICAL HEMOLYTIC UREMIC SYNDROME (aHUS)
    ESTUDIO DE FASE III, MULTICÉNTRICO Y DE UN SOLO GRUPO PARA EVALUAR LA EFICACIA, LA SEGURIDAD, LA FARMACOCINÉTICA Y LA FARMACODINÁMICA DE
    CROVALIMAB EN PACIENTES PEDIÁTRICOS CON SÍNDROME HEMOLÍTICO URÉMICO ATÍPICO (SHUa)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study Evaluating the Efficacy and Safety of Crovalimab in Pediatric Patients with Atypical Hemolytic Uremic Syndrome (aHUS)
    Un estudio que evalúa la eficacia y seguridad de crovalimab en pacientes pediátricos con síndrome urémico hemolítico atípico (SHUa)
    A.4.1Sponsor's protocol code numberBO42354
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/124/2021
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorRoche Farma S. A. que realiza el ensayo en España y que actúa como representante F. Hoffmann-La Roche Ltd
    B.1.3.4CountrySwitzerland
    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 supportF. Hoffman-La Roche Ltd.
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF.Hoffmann-La Roche Ltd.
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4047
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number+349132557300
    B.5.5Fax number+34913248196
    B.5.6E-mailspain.start_up_unit@roche.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 nameCrovalimab
    D.3.2Product code RO7112689/F03-10
    D.3.4Pharmaceutical form Solution for injection/infusion
    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 INNCROVALIMAB
    D.3.9.2Current sponsor codeRO7112689
    D.3.9.3Other descriptive nameC5 inh MAb, SKY59, RO/CH7092230
    D.3.9.4EV Substance CodeSUB197998
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number170
    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: 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 nameCrovalimab
    D.3.2Product code RO7112689/F03-01
    D.3.4Pharmaceutical form Solution for injection/infusion
    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 INNCROVALIMAB
    D.3.9.2Current sponsor codeRO7112689
    D.3.9.3Other descriptive nameC5 inh MAb, SKY59, RO/CH7092230
    D.3.9.4EV Substance CodeSUB197998
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number170
    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.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
    Atypical Hemolytic Uremic Syndrome (aHUS)
    Síndrome hemolítico urémico atípico (SHUa)
    E.1.1.1Medical condition in easily understood language
    aHUS is a rare disease, characterized by damage to the lining of small blood vessels, leading to red blood cell destruction, blood clots, and kidney damage.
    El SHUa es una enfermedad poco común, caracterizada por daño en el revestimiento de los vasos sanguíneos pequeños, lo que lleva a la destrucción de glóbulos rojos, coágulos de sangre y daño renal.
    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 20.1
    E.1.2Level LLT
    E.1.2Classification code 10079841
    E.1.2Term Atypical hemolytic uremic syndrome
    E.1.2System Organ Class 100000004851
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To evaluate the effect of crovalimab in complement inhibitor treatment-naive (Naive) patients
    • Evaluar el efecto de crovalimab en pacientes sin tratamiento previo con inhibidores del complemento (Naive)
    E.2.2Secondary objectives of the trial
    • To evaluate the effect of crovalimab in Naive and Switch (switching from either eculizumab or ravulizumab treatment to crovalimab) patients
    • To evaluate the overall safety and tolerability of crovalimab
    • To evaluate the pharmacokinetics of crovalimab as well as confirm the dosing strategy for patients weighing < 40 kilograms (kg)
    • To evaluate the immune response to crovalimab
    • Evaluar el efecto de crovalimab en pacientes Naive y Switch (cambio de tratamiento con eculizumab o ravulizumab a crovalimab)
    • Evaluar la seguridad y tolerabilidad generales del crovalimab.
    • Evaluar la farmacocinética de crovalimab y confirmar la estrategia de dosificación para pacientes que pesan <40 kilogramos (kg)
    • Evaluar la respuesta inmune al crovalimab
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    In addition to Naive and Switch patients (described above), Pretreated patients (patients who previously received treatment and then discontinued either eculizumab or ravulizumab and/or with a known C5 single nucleotide polymorphism [SNP]) will be enrolled as a separate third Cohort.
    For ALL (Naive, Switch, and Pretreated) Cohorts:
    • Age >=28 days and <18 years (at the time of signing the Informed Consent Form or Assent Form)
    • Body weight >=5 kg at screening
    • Vaccination against Neisseria meningitidis < 3 years prior to initiation of study treatment, in accordance with current local guidelines or standard-of-care, as applicable in patients with complement deficiency
    • For female patients of childbearing potential, an agreement to remain abstinent or use contraception
    • Patients with a prior kidney transplant are eligible, if they have a known history of complement-mediated aHUS prior to the kidney transplant
    For Naive Cohort ONLY:
    • Onset of thrombotic microangiopathy (TMA) <=28 days prior to first crovalimab administration
    For Switch Cohort ONLY:
    • Documented treatment with either eculizumab or ravulizumab, according to the local product label for aHUS. Patients switching from IV eculizumab must have received treatment for at least 90 days. Patients switching from IV ravulizumab must have received at least two maintenance doses.
    • Clinical evidence of response to either eculizumab or ravulizumab
    For Pretreated Cohort only:
    • If TMA is present at time of screening: First crovalimab administration <=28 days from onset of TMA recurrence
    • Received and subsequently discontinued treatment with either eculizumab or ravulizumab, for a minimum of 5.5 drug half-lives
    • For C5 SNP patients: Known C5 polymorphism AND documented treatment with either eculizumab or ravulizumab for aHUS, with poorly controlled TMA
    Además de los pacientes sin tratamiento previo, con cambio de tratamiento, los pacientes pretratados (pacientes que recibieron tratamiento previamente y luego suspendieron eculizumab o ravulizumab y / o con un polimorfismo de nucleótido único [SNP] C5 conocido) se inscribirán como una tercera cohorte separada
    En TODAS las cohortes (cohortes sin tratamiento previo, con cambio de tratamiento y con
    tratamiento previo):
    •Edad de entre >= 28 días y < 18 años en el momento de firmar el documento de
    consentimiento informado o el documento de asentimiento.
    •Peso >=5 kg en el momento de la selección
    •Vacunación contra Neisseria meningitidis < 3 años antes del inicio del tratamiento del estudio , de acuerdo con las pautas locales vigentes o el estándar de atención, según corresponda en pacientes con deficiencia del complemento
    •Mujeres con capacidad de procrear: compromiso de practicar la abstinencia sexual o de usar métodos anticonceptivos
    •Podrán participar en el estudio pacientes con un trasplante renal previo que tengan antecedentes conocidos de SHUa mediado por el complemento antes del trasplante renal
    Solo en la cohorte sin tratamiento previo:
    •Aparición de la MAT <= 28 días antes de la primera administración de crovalimab
    Solo en la cohorte de cambio de tratamiento:
    •Tratamiento documentado con eculizumab o ravulizumab conforme a la ficha técnica local del producto para el SHUa. Tratamiento con eculizumab recibido durante al menos 90 días hasta el día 1 del tratamiento del estudio. Los pacientes que cambien de ravulizumab i.v. deberán haber recibido al menos dos dosis de mantenimiento, hasta el día 1 del tratamiento del estudio.
    • Signos clínicos de respuesta a eculizumab o ravulizumab,
    Solo en la cohorte con tratamiento previo:
    •Si hay MAT en el momento de la selección: aparición de recidiva de la MAT <=28 días antes de la primera administración de crovalimab.
    •Recepción y posterior suspensión del tratamiento con eculizumab o ravulizumab durante
    un mínimo de 5,5 semividas del fármaco.

    .•Pacientes con PNS de C5: polimorfismo de C5 conocido (p. ej., Arg885) Y tratamiento documentado con eculizumab o ravulizumab para el SHUa, con MAT mal controlada,
    según la evaluación del investigador
    E.4Principal exclusion criteria
    For ALL (Naive, Switch, and Pretreated) Cohorts:
    • At TMA onset, diagnosis of thrombotic thrombocytopenic purpura (TTP), diagnosis of Shiga toxin–producing Escherichia coli hemolytic uremic syndrome (STEC-HUS), clinical suspicion of pneumococcal HUS, TMA secondary to cobalamin C defect or TMA related to diacylglycerol kinase-E (DGKE) nephropathy
    • TMA associated with non-aHUS related renal disease
    • Positive direct Coombs test
    • Identified drug exposure-related TMA
    • History of organ transplant, other than kidney transplant
    • Chronic dialysis, and/or end stage renal disease (ESRD)
    • History of a kidney disease other than aHUS, affecting renal function
    • History of Neisseria meningitidis infection within 6 months prior to screening and up to the first drug administration
    • Known or suspected immune deficiency (e.g., history of frequent recurrent infections)
    • Positive human immunodeficiency virus (HIV) test
    • Life expectancy of < 4 weeks
    • Active systemic bacterial, viral, or fungal infection within 14 days before first drug administration
    • Presence of fever (>=38 Degrees Celsius) within 7 days before the first drug administration
    • Patient with active or evolving multisystem organ dysfunction or failure
    • Immunized with a live attenuated vaccine within 1 month before first drug administration
    • Known systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), or anti-phospholipid antibody positivity or syndrome
    • Patients receiving chronic intravenous immunoglobulin (IVIg) within 8 weeks prior to start of screening, unless for unrelated medical condition
    • Female patients who are pregnant, breastfeeding, or have the intention of becoming pregnant during the study or within 6 months after the final dose of the study treatment
    • Splenectomy < 6 months prior to screening
    • Use of tranexamic acid within 7 days prior to screening
    • Concurrent disease, treatment, procedure or surgery, or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose any additional risk for the patient, or would, in the opinion of the investigator, preclude the patient's safe participation in and completion of the study
    For Naive Cohort ONLY:
    • Current or previous treatment with a complement inhibitor
    For Switch Cohort ONLY:
    • Positive for hepatitis B surface antigen (HBsAg) at screening
    • Positive for hepatitis C virus (HCV) antibody at screening
    • History of or ongoing cryoglobulinemia at screening
    En TODAS las cohortes (cohortes sin tratamiento previo, con cambio de tratamiento y con
    tratamiento previo):
    • Al inicio de MAT, diagnóstico de púrpura trombocitopénica trombótica (PTT), diagnóstico de síndrome urémico hemolítico de Escherichia coli productora de toxina Shiga (STEC-SUH), sospecha clínica de SUH neumocócico, MAT secundaria a defecto de cobalamina C o MAT relacionada con diacilglicerol quinasa-E (DGKE) nefropatía
    • MAT asociada a nefropatía no relacionada con el SHUa.
    • Prueba de Coombs directa positiva.
    • MAT relacionada con la exposición al fármaco identificada.
    • Antecedentes de trasplante de órganos, distinto del trasplante de riñón.
    • Diálisis crónica y/ o nefropatía terminal
    • Antecedentes de enfermedad renal distinta del SHUa que afecte a la función renal,
    • Antecedentes de infección por N. meningitidis en los 6 meses previos a la selección y hasta la primera administración del fármaco.
    • Inmunodeficiencia conocida o sospecha de esta (p. ej., antecedentes de infecciones recurrentes frecuentes).
    • Prueba del VIH positiva.
    • Esperanza de vida < 4 semanas
    • Infección bacteriana, vírica o micótica sistémica activa en los 14 días previos a la primera
    administración del fármaco.
    • Presencia de fiebre (>=38 Degrees Celsius ) en los 7 días previos a la primera administración del fármaco.
    • Pacientes con disfunción o insuficiencia multiorgánica activa o en evolución.
    • Vacunación con una vacuna de microorganismos vivos atenuados en el mes previo a la primera administración del fármaco.
    • Esclerosis sistémica (esclerodermia), lupus eritematoso sistémico o positividad o síndrome de anticuerpos antifosfolipídicos conocidos.
    • Tratamiento crónico con inmunoglobulina intravenosa (Ig i.v.) en las 8 semanas previas al
    comienzo de la selección, a menos que se trate de un proceso médico no relacionado.
    • Pacientes mujeres que están embarazadas, amamantando o tienen la intención de quedar embarazadas durante el estudio o dentro de los 6 meses posteriores a la dosis final del tratamiento del estudio.
    • Esplenectomía < 6 meses antes de la selección
    •Uso de ácido tranexámico en los 7 días previos a la selección.
    • Enfermedad concurrente, tratamiento, procedimiento o cirugía, o anomalía en las evaluaciones analíticas que pueda interferir en el desarrollo del estudio, que suponga un
    riesgo adicional para el paciente o que pueda, en opinión del investigador o el promotor, impedir la participación segura del paciente en el estudio y la finalización del estudio
    pacientes sin tratamiento previo
    • Tratamiento actual o previo con un inhibidor del complemento para los pacientes que cambien de tratamiento:
    • Positividad en la prueba de detección de antígenos de superficie del virus de la hepatitis B (HBsAg) en el momento de la selección.
    • Positividad para el virus de Hepatitis C (HCV) en el momento de la selección.
    • Antecedentes de crioglobulinemia en curso en el momento del cribado
    E.5 End points
    E.5.1Primary end point(s)
    1. Proportion of patients with cTMAr
    1. Proporción de pacientes con cTMAr
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Baseline to Week 25
    1. Visita basal a la semana 25
    E.5.2Secondary end point(s)
    For Naive and Switch Cohorts:
    1. Change from baseline to Week 25 in dialysis requirement status
    2. Observed value and change from baseline in estimated glomerular filtration rate (eGFR)
    3. Proportion of patients with change from baseline in chronic kidney disease (CKD) stage classified as improved, stable (no change), or worsened based on the National Kidney Foundation Chronic Kidney Disease Stage
    4. Observed value and change from baseline in hematologic parameters
    5. Incidence and severity of adverse events
    6. Change in targeted vital signs and clinical laboratory test results
    7. Incidence and severity of injection site reactions, infusion related reactions, hypersensitivity, malignant hypertension, and infections
    8. Incidence of adverse events leading to study drug discontinuation
    9. Serum concentration of crovalimab
    10. Prevalence and incidence of anti-drug antibodies (ADAs) to crovalimab
    11. Change in serum creatinine from baseline
    12. Change from baseline in fatigue as measured by the Pediatric Quality of Life Inventory (PedsQLTM) Multidimensional Fatigue Scale (MFS) and physical functioning as measured by the PedsQL Core in pediatric patients aged 2 to < 18 years old
    13. Change from baseline in physical functioning and physical symptoms as measured by the PedsQL Infant Scale in pediatric patients under 2 years old
    14. Change from baseline in the number of missed days of daycare or school
    15. For patients who discontinue crovalimab, describe the clinical course of patients who discontinue crovalimab after achieving cTMAr
    For Naive and Pretreated Cohorts:
    16. Proportion of patients with platelet count >= LLN
    17. Proportion of patients with normalization of LDH
    18. Proportion of patients with >=25% decrease in serum creatinine from baseline
    19. Time to complete TMA response (cTMAr)
    20. Duration of cTMAr, among patients who achieved cTMAr
    21. Proportion of patients with cTMAr
    22. Proportion of patients with increase in hemoglobin >=20 g/L, in the absence of a transfusion
    For Switch Cohort ONLY:
    23. Proportion of patients with maintained TMA control (mTMAc) from baseline through Week 25
    24. Incidence and severity of clinical manifestations of drug-target-drug complexes (DTDCs) in patients who switched to crovalimab treatment from either eculizumab or ravulizumab treatment
    25. Serum concentration of eculizumab or ravulizumab
    26. In adolescents (12 - 17 years), proportion of patients with preference for crovalimab, after switching from eculizumab or ravulizumab, as assessed by a Patient Preference Questionnaire (PPQ) developed by the Sponsor
    27. In children younger than 12 years old, proportion of caregivers with preference for crovalimab, after switching from eculizumab or ravulizumab, as assessed by the caregiver-reported version of the PPQ developed by the Sponsor
    En las cohortes sin tratamiento previo y de cambio de tratamiento:
    1. Cambio del estado inicial a la semana 25 en el estado de los requisitos de diálisis
    2. Valor observado y cambio desde el inicio en la tasa de filtración glomerular estimada (eGFR)
    3. Proporción de pacientes con cambios desde el inicio en el estadio de la enfermedad renal crónica (ERC) clasificados como mejorado, estable (sin cambios) o empeorado según el estadio de la enfermedad renal crónica de la National Kidney Foundation
    4. Valor observado y cambio desde el inicio en los parámetros hematológicos
    5. Incidencia y gravedad de los eventos adversos
    6. Cambio en los signos vitales específicos y los resultados de las pruebas de laboratorio clínico
    7. Incidencia y gravedad de las reacciones en el lugar de la inyección, reacciones relacionadas con la infusión, hipersensibilidad, hipertensión maligna e infecciones.
    8. Incidencia de eventos adversos que llevaron a la interrupción del fármaco del estudio
    9. Concentración sérica de crovalimab
    10. Prevalencia e incidencia de anticuerpos antidrogas (ADA) contra crovalimab
    11. Cambio en la creatinina sérica desde el inicio
    12. Cambio desde el inicio en la fatiga según lo medido por la Escala multidimensional de fatiga (MFS) del Inventario de calidad de vida pediátrica (PedsQLTM) y el funcionamiento físico según lo medido por el PedsQL Core en pacientes pediátricos de 2 a <18 años
    13. Cambio desde el inicio en el funcionamiento físico y los síntomas físicos medidos por la Escala infantil PedsQL en pacientes pediátricos menores de 2 años
    14. Cambio con respecto a la línea de base en la cantidad de días perdidos de guardería o escuela
    15. Para los pacientes que interrumpen el tratamiento con crovalimab, describa la evolución clínica de los pacientes que interrumpen el tratamiento con crovalimab después de lograr cTMAr.
    Para cohortes sin tratamiento y pretratadas:
    16. Proporción de pacientes con recuento de plaquetas> = LIN
    17. Proporción de pacientes con normalización de LDH
    18. Proporción de pacientes con> = 25% de disminución de la creatinina sérica desde el inicio
    19. Tiempo para completar la respuesta de TMA (cTMAr)
    20. Duración de cTMAr, entre los pacientes que lograron cTMAr
    21. Proporción de pacientes con cTMAr
    22. Proporción de pacientes con aumento de hemoglobina> = 20 g / L, en ausencia de transfusión
    Solo en la cohorte de cambio de tratamiento:
    23. Proporción de pacientes con control de MAT mantenido (mTMAc) desde el inicio hasta la semana 25
    24. Incidencia y gravedad de las manifestaciones clínicas de los complejos fármaco-objetivo-fármaco (DTDC) en pacientes que cambiaron al tratamiento con crovalimab desde el tratamiento con eculizumab o con ravulizumab
    25. Concentración sérica de eculizumab o ravulizumab
    26. En adolescentes (12 a 17 años), proporción de pacientes con preferencia por crovalimab, después de cambiar de eculizumab o ravulizumab, según la evaluación de un Cuestionario de preferencias del paciente (PPQ) desarrollado por el Patrocinador.
    27. En niños menores de 12 años, proporción de cuidadores que prefieren crovalimab, después de cambiar de eculizumab o ravulizumab, según la evaluación de la versión del PPQ informada por el cuidador desarrollada por el patrocinador
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Baseline to Week 25
    2-9. Up to 8 years
    10. At baseline (prevalence) and up to 8 years (incidence)
    11-15. Up to 8 years
    16-18. At Week 25
    19-20. Up to 8 years
    21-23. At Week 25
    24. From baseline to Week 13
    25. Day 1
    26-27. At Week 17
    1. Visita basal a la semana 25
    2-9. Hasta 8 años
    10. Al inicio del estudio (prevalencia) y hasta los 8 años (incidencia)
    11-15. Hasta 8 años
    16-18. En la semana 25
    19-20. Hasta 8 años
    21-23. En la semana 25
    24. Desde el inicio hasta la semana 13
    25. Día 1
    26-27. En la semana 17
    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 No
    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 concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA11
    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
    Brazil
    Canada
    China
    Israel
    Japan
    South Africa
    United States
    Belgium
    France
    Hungary
    Italy
    Poland
    Spain
    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
    The end of this study is defined as the date when the last patient’s last visit occurs or the date at which the last data point required for the final statistical analysis is collected, whichever occurs last.
    El final de este estudio se define como la fecha en que se produce la última visita del último paciente o la fecha en la que se recopila el último punto de datos requerido para el análisis estadístico final, lo que ocurra en último lugar.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days8
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months5
    E.8.9.2In all countries concerned by the trial days8
    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: 40
    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: 6
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 17
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 12
    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 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
    Minors
    Menores
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 12
    F.4.2.2In the whole clinical trial 35
    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 Sponsor will offer continued access to Roche IMP (crovalimab) free of charge to eligible patients in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product. http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf
    El Promotor ofrecerá acceso continuo a Roche IMP (crovalimab) de forma gratuita a los pacientes elegibles de acuerdo con la Política global de Roche sobre acceso continuo a medicamentos en investigación. http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf
    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 Decision2021-09-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-09-21
    P. End of Trial
    P.End of Trial StatusOngoing
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