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    Summary
    EudraCT Number:2019-003924-19
    Sponsor's Protocol Code Number:RVT-1401-2003
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Temporarily Halted
    Date on which this record was first entered in the EudraCT database:2020-01-14
    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 number2019-003924-19
    A.3Full title of the trial
    A Phase 2, Multicenter, Non-Randomized, Open-Label Study of RVT-1401 for the Treatment of Patients with Warm Autoimmune Hemolytic Anemia
    Estudio de fase 2, multicéntrico, no aleatorizado y abierto, de RVT- 01 en el tratamiento de pacientes con anemia hemolítica autoinmune por autoanticuerpos calientes
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Non-randomized, open-label study to investigate the efficacy, safety and tolerability of RVT-1401 for the Treatment of Patients with Warm Autoimmune Hemolytic Anemia
    Estudio no aleatorizado y abierto, para investigar la eficacia, seguridad y tolerabilidad de RVT-1401 para el tratamiento de pacientes con anemia hemolítica autoinmune por autoanticuerpos calientes
    A.3.2Name or abbreviated title of the trial where available
    ASCEND-WAIHA
    A.4.1Sponsor's protocol code numberRVT-1401-2003
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorImmunovant Sciences GmbH
    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 supportImmunovant Sciences GmbH
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationImmunovant Sciences GmbH
    B.5.2Functional name of contact pointVP Regulatory Affairs
    B.5.3 Address:
    B.5.3.1Street AddressViaduktstrasse 8
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4051
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number+1-917-565-9138
    B.5.6E-mailbagyashree.sundaram@immunovant.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 nameRVT-1401
    D.3.2Product code RVT-1401
    D.3.4Pharmaceutical form Solution for injection
    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 INNRVT-1401
    D.3.9.3Other descriptive nameRVT-1401
    D.3.9.4EV Substance CodeSUB180804
    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
    Warm Autoimmune Hemolytic Anemia
    Anemia hemolítica autoinmune por autoanticuerpos calientes
    E.1.1.1Medical condition in easily understood language
    Warm Autoimmune Hemolytic Anemia
    Anemia hemolítica autoinmune por autoanticuerpos calientes
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10003825
    E.1.2Term Autoimmune hemolytic anemia
    E.1.2System Organ Class 100000004851
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To examine the effect of RVT-1401 on proportion of responders (defined as Hb level ≥10g/dL with at least a ≥2 g/dL increase from baseline without rescue therapy or blood transfusions in the previous two weeks).
    To assess the safety and tolerability of RVT-1401 in subjects with WAIHA
    Examinar el efecto de RVT-1401 sobre el porcentaje de respondedores (definidos como los sujetos con un valor de Hb ≥10 g/dL y como mínimo un aumento ≥2 g/dL frente al basal sin tratamiento de rescate o transfusiones de sangre en las dos semanas previas).

    Evaluar la seguridad y la tolerabilidad de RVT-1401 en sujetos con anemia hemolítica autoinmune por
    autoanticuerpos calientes
    E.2.2Secondary objectives of the trial
    To examine the effect of RVT-1401 on change in Hb levels
    To examine the effect of RVT-1401 on time to response
    To examine the effect of RVT-1401 on change in hematocrit levels
    To examine the effect of RVT-1401 on proportion of participants with Hb levels in the normal range
    To examine the effect of RVT-1401 on time to achieving Hb levels in the normal range
    To examine the effect of RVT-1401 on change in fatigue
    To examine the effect of RVT-1401 on change in dyspnea
    To examine the effect of RVT-1401 on change in health-related quality of life
    To assess the change in serum levels of total IgG & IgG subclasses (I-IV)
    To examine RVT-1401 PK following repeated doses in patients with WAIHA
    To assess the changes in LDH, bilirubin,haptoglobin
    To measure anti-RVT-1401 antibodies following repeated doses in patients with WAIHA
    -Examinar el efecto de RVT-1401 sobre: el cambio en los valores de Hb, el tiempo hasta la respuesta, el cambio en los valores de hematocrito, sobre el porcentaje de participantes con valores de Hb dentro de la normalidad, el tiempo hasta alcanzar unos valores de Hb dentro de la normalidad, el cambio en el cansancio, el cambio en la disnea y sobre el cambio en la calidad de vida relacionada con la salud. - Evaluar el cambio en los niveles séricos de IgG total y subclases de IgG (I-IV). - Examinar la farmacocinética de RVT-1401 tras la administración de dosis repetidas en pacientes con anemia hemolítica autoinmune por autoanticuerpos calientes. - Evaluar los cambios en LDH, bilirrubina y haptoglobina. -Determinar los anticuerpos anti-RVT-1401 tras la administración de dosis repetidas en pacientes con anemia hemolítica autoinmune por autoanticuerpos calientes.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female ≥ 18 years of age.
    2. Diagnosis of primary or secondary WAIHA as documented by a positive direct antiglobulin test (DAT) specific for anti-IgG alone or anti-IgG plus C3d.
    3. Secondary WAIHA may only include Stage 0 chronic lymphocytic leukemia (CLL) in which separate treatment is not indicated, nor anticipated to require active management for the duration of the study.
    4. Have failed or not tolerated at least one prior WAIHA treatment regimen as per local standards (e.g., steroids, rituximab, azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil (MMF), danazol, or vincristine).
    5. Participants with splenectomy ≥3 months from Day 1 who are up to date on vaccinations (based on age and local guidance) are allowed.
    6. Haptoglobin < lower limit of normal (LLN) and lactate dehydrogenase (LDH) >upper limit of normal (ULN).
    7. At Screening and Baseline, subject's hemoglobin level must be <10 g/dL and the subject must have documented symptoms related to anemia (e.g., weakness, dizziness, fatigue, shortness of breath, chest pain).
    8. Karnofsky Performance status ≥ 60.
    9. Subject's concurrent treatment for WAIHA may consist only of steroids (stable dose for at least two weeks prior to Day 1), immunosuppressant therapy (azathioprine, MMF, or cyclosporine) that has been at a stable dose for at least four weeks prior to Day 1, or erythropoietin (stable dose for at least 6 weeks prior to Day 1). [Note: starting doses of WAIHA therapy must be maintained throughout the study except in the case of a rescue medication as per local standards for safety. Steroid taper down to 10 mg/day will be allowed for participants who achieve response for at least 2 weeks.]
    10. A female participant is eligible to participate if she is of:
    a. Non-childbearing potential defined as pre-menopausal females with a documented bilateral tubal ligation, bilateral oophorectomy (removal of the ovaries) or hysterectomy; hysteroscopic sterilization, or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) in the post-menopausal range is confirmatory].
    b. Child-bearing potential and agrees to use one of the contraception methods listed in Section 6.6.1 for an appropriate period of time (as determined by the product label or Principal Investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female participants must agree to use contraception until 90 days after the last dose of study treatment.
    11. Male participants must agree to use one of the contraception methods listed in Section 6.6.1. This criterion must be followed from the time of the first dose of study treatment until 90 days after the last dose of study treatment.
    12. Willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
    1. Hombre o mujer ≥ 18 años de edad.
    2. Diagnóstico de anemia hemolítica autoinmune por autoanticuerpos calientes (WAIHA), primaria o secundaria, documentada por la positividad de un test de antiglobulina directa (direct antiglobulin test, DAT) específico para anti-IgG sola o para anti-IgG más C3d.
    3. La WAIHA secundaria sólo puede incluir la leucemia linfocítica crónica (chronic lymphocytic leukemia, CLL) en Estadio 0 en la que no esté indicado un tratamiento separado o no se prevea que precise tratamiento activo durante el estudio.
    4. Fracaso o intolerancia a como mínimo un tratamiento previo para la WAIHA (por ejemplo, corticosteroides, rituximab, azatioprina, ciclofosfamida, ciclosporina, micofenolato mofetilo (MMF), danazol o vincristina). El fracaso se define como empeoramiento o enfermedad refractaria a pesar de los esteroides y/o inmunosupresores.
    5. Se permiten los pacientes con esplenectomía ≥3 meses antes del Día 1 que se encuentren al día en cuanto a sus vacunas (según edad y recomendaciones locales).
    6. Haptoglobina < límite inferior de la normalidad (lower limit of normal, LLN) y deshidrogenasa láctica (LDH) > límite superior de la normalidad (upper limit of normal, ULN).
    7. En los exámenes de Selección y en el Basal, el sujeto debe presentar una hemoglobina <10 g/dL y síntomas documentados de anemia (por ejemplo, debilidad, mareo, cansancio, disnea, dolor torácico).
    8. Estado funcional de Karnofsky ≥ 60.
    9. El tratamiento concomitante del sujeto por su WAIHA solamente puede consistir en corticoides (a una dosis estable durante como mínimo las dos semanas anteriores al Día 1), tratamiento inmunosupresor (azatioprina, MMF o ciclosporina) que se ha mantenido a una dosis estable durante como mínimo las cuatro semanas anteriores al Día 1, o eritropoyetina (a una dosis estable durante como mínimo 6 semanas antes del Día 1). [Nota: las dosis de inicio del tratamiento para la WAIHA deberán mantenerse durante el estudio, excepto en caso de medicación de rescate de acuerdo a las normas locales por razón de seguridad. Se permitirá la reducción de los corticoides a 10 mg/día en los participantes que alcancen respuesta durante como mínimo 2 semanas.]
    10. En el caso de mujeres, podrán participar si:
    a. No son potencialmente fértiles, lo que se define como aquellas mujeres premenopáusicas con historia documentada de ligadura de trompas bilateral, ovariectomía bilateral o histerectomía; esterilización histeroscópica; o posmenopausia, definida como 12 meses de amenorrea espontánea (en los casos dudosos, se precisa confirmación mediante determinación simultánea de niveles en sangre de hormona folículo-estimulante (FSH) en el rango posmenopáusico].
    b. Son potencialmente fértiles pero han estado utilizando uno de los métodos anticonceptivos que se listan en la Sección 6.6.1 durante el periodo de tiempo adecuado (según ficha técnica del producto o el Investigador Principal) antes del comienzo del tratamiento para reducir pertinentemente el riesgo de embarazo en ese momento. Las participantes fértiles deben mostrar su conformidad en utilizar el método anticonceptivo hasta 90 días después de la última dosis del tratamiento del estudio.
    11. Los varones deben mostrar su conformidad en utilizar uno de los métodos anticonceptivos que se listan en la Sección 6.6.1, desde el momento de la primera dosis del tratamiento del estudio y hasta 90 días después de la última dosis del tratamiento del estudio.
    12. Conformidad en y capacidad de otorgar su consentimiento informado por escrito, lo que incluye el cumplimiento con los requisitos y las restricciones que se listan en dicho documento de consentimiento.
    E.4Principal exclusion criteria
    1. Participants with other types of AIHA (e.g., cold antibody AIHA, cold agglutinin syndrome, mixed type AIHA, or paroxysmal cold hemoglobinuria).
    2. Participants requiring more than 2 units of RBC per week in the 2 weeks prior to Screening and Baseline.
    3. Use of rituximab, any monoclonal antibody for immunomodulation, or proteasome inhibitor, within the past 3 months prior to Screening.
    4. Immunoglobulins given by SC, IV (IVIG), or intramuscular route, or plasmapheresis/plasma exchange (PE) within 60 days before Screening.
    5. Total IgG level <6 g/L (at Screening).
    6. Absolute neutrophil count <1000 cells/mm3(at Screening).
    7. Albumin level <3.5 g/dL at Screening.
    8. Known advanced liver disease including any diagnosis of cirrhosis of any stage.
    Non- alcoholic fatty liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) is allowable if there has been a recent (within 6 months) normal ultrasound, CT, or MRI. If the ultrasound, CT, or MRI demonstrate fatty changes alone, the participant may be enrolled if s/he has a normal range fibroscan for liver fibrosis.
    9. AST or ALT ≥1.5x ULN at Screening.
    The participant may only be enrolled if s/he has a recent (within 6 months) normal ultrasound, CT, or MRI. If the ultrasound, CT, or MRI demonstrate fatty changes alone, the participant may be enrolled if s/he has a normal range fibroscan for liver fibrosis.
    10. Participant has any laboratory abnormality (at screening) that, in the opinion of the investigator, is clinically significant, has not resolved at baseline, and could jeopardize or would compromise the participant's ability to participate in this study.
    11. Medical history of primary immunodeficiency, T-cell or humoral, including common variable immunodeficiency.
    12. Have an active infection, a recent serious infection (i.e., requiring injectable antimicrobial therapy or hospitalization) within the 8 weeks prior to Screening.
    13. History of or known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or Mycobacterium tuberculosis:
    - Participants must have negative test results for HBV surface antigen, HBV core antibody, HIV 1 and 2 antibodies, and a negative QuantiFERON-TB Gold test at Screening.
    - Participants with an indeterminate QuantiFERON-TB Gold test result will be allowed one retest; if not negative on retesting, the participant will be excluded.
    14. Infection with hepatitis C virus (HCV):
    - Participants must have a negative test result for HCV antibody.
    or
    - Participants with a known history of HCV must have documented evidence of sustained virologic response that is consistent with cure of hepatitis C infection. This is defined as undetectable or unquantifiable HCV RNA at least 12 weeks after stopping HCV treatment (HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C; 2014-2018, AASLD and IDSA). This should be confirmed with a negative HCV RNA test at Screening.
    15. Active malignancy or history of malignancy in the 3 years prior to screening (exclusive of non-melanoma skin cancer and cervical cancer in situ).
    16. Participant has any medical condition (acute or chronic illness) or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the participant's ability to participate in this study.
    17. Body Mass Index (BMI) at Screening ≥ 40 kg/m2.
    18. Use of investigational drug within 60 days or 5 half-lives of the drug (whichever is longer) before Screening.
    19. Participant has received a live vaccination within 2 weeks prior to the Baseline Visit; or intends to have a live vaccination during the course of the study or within 7 weeks following the final dose of study treatment.
    20. History of sensitivity to any of the study treatments, or components thereof or a history of anaphylaxis (i.e., serious, life-threatening allergic reactions) that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
    21. Pregnant or lactating females as determined by positive serum or urine human chorionic gonadotropin test at screening or baseline.
    22. QTcF interval >450 milliseconds for males and >470 milliseconds for females at Screening (a single repeat is allowed for eligibility determination). QTcF >480 msec in participants with Bundle Branch Block.
    23. Diagnosis of concomitant idiopathic thrombocytopenia purpura (ITP)/ Evans syndrome with platelet count <100,000.
    1. Participantes con otros tipos de anemia hemolítica autoinmune (AIHA) (por ejemplo, por anticuerpos fríos, síndrome de aglutininas frías, de tipo mixto o hemoglobinuria paroxística por frío). 2. Participantes que hayan precisado más de 2 uds. de concentrado de hematíes por semana en las 2 semanas previas a la Selección y al Basal. 3. Uso de rituximab, cualquier anticuerpo monoclonal para inmunomodulación o inhibidor de la proteasa, en el plazo de los 3 meses anteriores a la Selección. 4. Inmunoglobulinas, administradas por vía SC, IV (IVIG) o intramuscular, o plasmaféresis/ intercambio plasmático (plasma Exchange, PE) en el plazo de los 60 días anteriores a la Selección.
    5. IgG total <6 g/L (en la Selección). 6. Recuento absoluto de neutrófilos <1000/mm3 (en la Selección).
    7. Albúmina <3,5 g/dL en la Selección. 8. Hepatopatía avanzada, incluido el diagnóstico de cirrosis en cualquier fase. Se permite la enfermedad por hígado graso no alcohólica (non- alcoholic fatty liver disease, NAFLD), incluida la esteatohepatitis no alcohólica (non-alcoholic steatohepatitis, NASH) en caso de ecografía, TAC o RM recientes normales (de los 6 meses anteriores). Si la ecografía, TAC o RM solamente mostraran cambios grasos, el sujeto podrá participar si tiene un fibroscan de rango normal para fibrosis hepática. 9. AST o ALT ≥1,5x ULN en la Selección. El participante solamente podrá entrar en el estudio si tiene un examen normal reciente (de los 6 meses anteriores) de ecografía, TAC o RM. Si la ecografía, TAC o RM solamente mostraran cambios grasos, el paciente podrá participar si tiene un fibroscan de rango normal para fibrosis hepática. 10. Participante con cualquier anomalía de laboratorio (en la Selección) que, en opinión del Investigador, es clínicamente importante, no se ha resuelto en el basal y pudiera poner en riesgo o afectar a la capacidad del sujeto para participar en este estudio. 11. Historia médica de inmunodeficiencia primaria, de células T o humoral, incluida la inmunodeficiencia variable común. 12. Infección activa o infección grave reciente (es decir, que ha precisado tratamiento antimicrobiano inyectable u hospitalización) en el plazo de las 8 semanas anteriores a la Selección. 13. Antecedente o infección conocida por el virus de la inmunodeficiencia humana (HIV), virus de la hepatitis B (HBV) o por Mycobacterium tuberculosis: - Los participantes deben mostrar negatividad en la Selección del antígeno de superficie del HBV, anticuerpo core del HBV y anticuerpos HIV 1 y 2, así como resultado negativo del QuantiFERON-TB Gold. A los sujetos con resultado indeterminado del QuantiFERON-TB Gold test se les podrá repetir una vez esta prueba; si no fuera negativa en la repetición, no podrán entrar en el estudio. 14. Infección por el virus de la hepatitis C (HCV): -Los participantes deberán presentar negatividad de anticuerpos frente al HCV,o bien - Los participantes con historia conocida de HCV deberán presentar evidencia documentada de respuesta virológica mantenida compatible con curación de su hepatitis C, lo que se define como: HCV RNA no detectable o no cuantificable como mínimo 12 semanas después de la suspensión del tratamiento para el HCV (HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C; 2014-2018, AASLD and IDSA). Debe confirmarse mediante negatividad del RNBA HCV en la Selección. 15. Neoplasia maligna activa o historia de neoplasia maligna en los 3 años anteriores a la Selección (se excluyen el cáncer cutáneo de tipo no melanoma y el cáncer de cuello uterino in situ). 16. Participante con cualquier proceso médico (agudo o crónico) o psiquiátrico que, en opinión del investigador, pudiera poner en riesgo o afectar a la capacidad del sujeto para participar en este estudio. 17. Índice de masa corporal (Body Mass Index, BMI) en la Selección ≥ 40 kg/m2. 18. Tratamiento con un fármaco experimental en el plazo de los 60 días o 5 semividas de dicho medicamento (eligiéndose el mayor) previos a la Selección. 19. Participante que ha recibido una vacuna con gérmenes vivos en el plazo de las 2 semanas anteriores a la visita Basal, o programado para recibir una vacuna de este tipo en el curso del estudio o en el plazo de las 7 semanas siguientes a la última dosis del tratamiento del estudio.
    20. Historia de hipersensibilidad a cualquiera de los tratamientos del estudio o a sus componentes, o historia de anafilaxia que, en opinión del investigador o del Monitor Médico, contraindica su participación. 21. Mujeres embarazadas o en lactancia natural, según se desprende de un resultado positivo (en suero u orina) de la gonadotropina coriónica humana en la Selección o en el Basal. 22. Intervalo QTcF >450 mseg en los varones y >470 mseg en las mujeres en la Selección (se permite una sola repetición para determinar la elegibilidad). QTcF >480 mseg en los sujetos con bloqueo de rama. 23. Diagnóstico concomitante de púrpura trombocitopénica idiopática/síndrome de Evans con plaquetas <100.000.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of responders at week 13
    Assessment of safety and tolerability by analysis of adverse event (AE) data and changes from baseline in vital signs, ECGs, and clinical laboratory values
    Porcentaje de respondedores en la semana 13.

    Evaluación de la seguridad y la tolerabilidad, mediante el análisis de los datos de acontecimientos adversos y de los cambios frente al basal en constantes vitales, ECG y determinaciones de laboratorio.
    E.5.1.1Timepoint(s) of evaluation of this end point
    week 13
    A la semana 13
    E.5.2Secondary end point(s)
    Change from baseline in Hb levels
    Time to response
    Change from baseline in hematocrit levels
    Proportion of participants with Hb levels in the normal range at week 13
    Time to achieving Hb levels in the normal range
    Change from baseline in FACIT-F score
    Change from baseline in Medical Research Council (MRC) breathlessness scale
    Change from baseline in EQ-5D-3L score
    Change from baseline in levels of total IgG & IgG subclasses (I-IV)
    Concentration of RVT-1401 pre-dose (Ctrough)
    Change from baseline in LDH, bilirubin, and haptoglobin
    Immunogenicity determined by change from pre-dose in anti-RVT-1401 antibodies, and characterization of any anti-RVT-1401 to confirm neutralization potential.
    Cambio frente al basal en los valores de Hb
    Tiempo hasta la respuesta
    Cambio frente al basal en los valores de hematocrito
    Porcentaje de participantes con valores de Hb dentro de la normalidad en la semana 13
    Tiempo hasta alcanzar unos valores de Hb dentro de la normalidad
    Cambio frente al basal en la puntuación de FACIT-F
    Cambio frente al basal en la escala de disnea del Medical
    Research Council (MRC)
    Cambio frente al basal en la puntuación de EQ-5D-3L
    Cambio frente al basal en los niveles de IgG total y de las subclases de IgG (I-IV)
    Concentraciones de RVT-1401 antes de la dosis (Ctrough)
    Cambio frente al basal en LDH, bilirrubina y haptoglobina
    Inmunogenia, determinada por el cambio frente a antes de la dosis en los anticuerpos anti-RVT-1401 y
    caracterización de los eventuales anticuerpos anti-RVT-1401 para confirmar su potencial neutralizante
    E.5.2.1Timepoint(s) of evaluation of this end point
    week 13
    A la semana 13
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    tolerability
    tolerabilidad
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    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 Yes
    E.8.2.3.1Comparator description
    Dosing Regimen A -680 mg weekly for 12 weeks; Dosing Regimen B - 340 mg weekly for 12 weeks
    E.8.2.4Number of treatment arms in the trial2
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    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
    Israel
    Korea, Republic of
    Romania
    Spain
    Thailand
    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
    LPLV
    Última visita del último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    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 No
    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) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 14
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 2
    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 No
    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 6
    F.4.2.2In the whole clinical trial 16
    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)
    Participants will not receive any additional treatment with the study treatment from the Sponsor after completion of the study because the long-term safety and efficacy of RVT-1401 have not been established.
    The Principal Investigator is responsible for ensuring that consideration has been given to the post-study care of the participant’s medical condition.
    Los pacientes no continuarán con el tratamiento del estudio del Promotor una vez finalizado el estudio porque aún no se han establecido la seguridad y eficacia de RVT-1401 a largo plazo.
    Es responsabilidad del Investigador Principal considerar la atención médica del participante después del estudio.
    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 Decision2020-05-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-03-24
    P. End of Trial
    P.End of Trial StatusTemporarily Halted
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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