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    Summary
    EudraCT Number:2020-005732-29
    Sponsor's Protocol Code Number:MOM-M281-011
    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:2021-08-26
    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 number2020-005732-29
    A.3Full title of the trial
    Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Nipocalimab Administered to Adults with Generalized Myasthenia Gravis
    Estudio en fase III, multicéntrico, aleatorizado, doble ciego, controlado con placebo para evaluar la eficacia, la seguridad, la farmacocinética y la farmacodinámica de nipocalimab administrado a adultos con miastenia grave generalizada
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Efficacy and Safety Study of Nipocalimab IV Infusions for Adults With Generalized Myasthenia Gravis
    Estudio de eficacia y seguridad de las infusiones i.v. de nipocalimab para adultos con miastenia grave generalizada
    A.4.1Sponsor's protocol code numberMOM-M281-011
    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 SponsorJanssen-Cilag International N.V.
    B.1.3.4CountryBelgium
    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 supportJanssen Research & Development, LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationJanssen-Cilag International N.V.
    B.5.2Functional name of contact pointClinical Registry Group
    B.5.3 Address:
    B.5.3.1Street AddressArchimedesweg 29
    B.5.3.2Town/ cityLeiden
    B.5.3.3Post code2333
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+31715242166
    B.5.5Fax number+31715242110
    B.5.6E-mailClinicalTrialsEU@its.jnj.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 nameNipocalimab
    D.3.2Product code JNJ-80202135
    D.3.4Pharmaceutical form Solution for 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 INNNipocalimab
    D.3.9.1CAS number 2211985-36-1
    D.3.9.2Current sponsor codeJNJ-80202135
    D.3.9.3Other descriptive nameM281
    D.3.9.4EV Substance CodeSUB195356
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Myasthenia gravis (MG).
    Miastenia grave (MG)
    E.1.1.1Medical condition in easily understood language
    Myasthenia gravis, a neuromuscular disease.
    Miastenia grave, una enfermedad neuromuscular
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10028417
    E.1.2Term Myasthenia gravis
    E.1.2System Organ Class 10029205 - Nervous system disorders
    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 efficacy of nipocalimab compared to placebo based on the Myasthenia Gravis-Activities of Daily Living (MG-ADL) scale, in
    seropositive generalized myasthenia gravis (gMG) participants when treatment is taken as directed.
    Evaluar la eficacia de nipocalimab en comparación con placebo con base en la escala de actividades de la vida diaria en la miastenia grave (AVD-MG), en participantes seropositivos con miastenia grave generalizada (MGg) cuando el tratamiento se toma según las indicaciones.
    E.2.2Secondary objectives of the trial
    - To evaluate the efficacy of nipocalimab compared to placebo based on the Quantitative Myasthenia Gravis (QMG) scale, in seropositive gMG
    participants when treatment is taken as directed.
    - To evaluate the clinically important individual response of nipocalimab compared to placebo based on the MG-ADL scale, in seropositive gMG participants when treatment is taken as directed.
    - To evaluate the efficacy of nipocalimab loading dose compared to placebo based on the MG-ADL scale, in seropositive gMG participants when treatment is taken as directed.
    - To evaluate the effect of nipocalimab compared to placebo on gMG symptom remission based on the MG-ADL scale, in seropositive gMG participants when treatment is taken as directed.
    -To evaluate sustainability of therapeutic response of nipocalimab
    compared to placebo based on the MGADL scale, in seropositive gMG participants when treatment is taken as directed.
    -Evaluar eficacia de nipocalimab comparado con placebo con base en escala cuantitativa de miastenia grave (Quantitative Myasthenia Gravis, QMG), en participantes seropositivos con MGg con tratamiento según las indicaciones.
    -Evaluar respuesta individual clínicamente importante de nipocalimab comparado con placebo con base en la escala AVD-MG, en participantes seropositivos con MGg con tratamiento según las indicaciones.
    -Evaluar eficacia de la dosis de carga de nipocalimab comparado con placebo con base en escala AVD-MG, en participantes seropositivos con MGg con tratamiento según las indicaciones.
    -Evaluar efecto de nipocalimab comparado con placebo en remisión de síntomas de MGg con base en escala AVD-MG, en participantes seropositivos con MGg con tratamiento según las indicaciones.
    - Evaluar sostenibilidad de respuesta terapéutica de nipocalimab comparado con placebo con base en escala AVD-MG, en participantes seropositivos con MGg con tratamiento según las indicaciones.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    RANDOMIZED PHASE:
    1. ≥18 years of age at the time of consent.
    2. Diagnosis of MG with generalized muscle weakness meeting the clinical criteria for gMG as defined by the MGFA Clinical Classification Class II a/b, III a/b, or IVa/b at screening.
    3. MG-ADL score of ≥6 at screening and baseline.
    4. Has suboptimal response to current stable therapy for gMG according to the investigator.
    Stable therapy is defined in the protocol.
    5. A participant using herbal, naturopathic, traditional Chinese remedies, ayurvedic or nutritional supplements, or medical marijuana is eligible if the use is acceptable to the investigator.
    6. Participants who have undergone splenectomy must be at least 3 months post resection prior to screening and must be vaccinated as per the United States Center for Disease Control and Prevention annual Recommended Immunization Schedule for Adults, United States. OR must be vaccinated as per country-specific guidelines or local regulations.
    7. Has sufficient venous access to allow drug administration by infusion and blood sampling as per the protocol.
    8. Is recommended to be up to date on all age-appropriate vaccinations prior to screening as per routine local medical guidelines.
    9. Man or woman (according to their reproductive organs and functions assigned by
    chromosomal complement).
    10. A woman of childbearing potential must have a negative highly sensitive serum at Screening and a negative urine pregnancy test at Day 1 prior to administration of study intervention.
    11. A woman must be
    a. Not of childbearing potential
    b. Of childbearing potential and
    - Practicing a highly effective, preferably user-independent method of contraception and agrees to remain on a highly effective method while receiving study intervention and until 60 days after last dose. The investigator should evaluate the potential for contraceptive method failure in relationship to the first dose of study intervention.
    12. A woman must agree not to donate eggs (ova, oocytes), or freeze for future use for the purposes of assisted reproduction, during the study and for a period of 30 days after the administration of study intervention.
    13. A male participant who is sexually active with a woman of childbearing potential and who has not had a vasectomy must agree to use a barrier method of birth control (eg, either a condom [with spermicidal foam/gel/film/cream/suppository if available in their locale] or a partner with an occlusive cap [diaphragm or cervical/vault caps] plus spermicidal foam/gel/film/cream/suppository if available in their local), during the study and for at least 90 days after receiving the last administration of study intervention.
    14. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum 90 days after receiving the last administration of study intervention.
    15. Must sign an ICF indicating that the participant understands the purpose of, and procedures required for, the study and is willing to voluntarily participate in the study and comply with all study procedures.
    16. Must be able to read and write.

    OLE PHASE:
    Participants who have completed the 24-week double-blind placebo-controlled phase are eligible to enter the OLE phase.
    Participants who had study intervention discontinued for a reason other than the need for hospitalization or rescue therapy (IVIG, plasmapheresis), and who completed the scheduled of assessments for the full 24-week double-blind placebo-controlled phase, may enter the OLE based on the investigator’s discretion.
    Participants affected by interruption of theMOM-M281-005 study due to the COVID 19 pandemic must meet the following Inclusion Criteria:
    1. The investigator has confirmed that the participant is not receiving, or has not received since the interruption of the Phase 2 study, any medication that might put the participant at risk when receiving nipocalimab or might interfere with the assessment of the safety of nipocalimab.
    2. Randomized inclusion point 6
    3. Randomized inclusion point 7
    4. Is recommended to be up to date on all age-appropriate vaccinations prior to screening as
    per routine local medical guidelines.
    5. Sex and Contraceptive/Barrier Requirements as outlined in Double-blind
    Placebo-Controlled Phase inclusion criteria # 9, #10, #11, #12, #13, and #14 above.
    6. Randomized inclusion point 15
    FASE DE RANDOMIZACION
    1.≥18 años en el momento de obtención del consentimiento.
    2.Diagnóstico de MG con debilidad muscular generalizada que cumpla los criterios clínicos de MGg según la definición de la clasificación clínica de la MGFA de clase II a/b, III a/b o IV a/b en la selección.
    3.Puntuación de AVD-MG ≥6 en la selección y al inicio.
    4.Respuesta insuficiente al tratamiento estable actual para MGg según investigador.El tratamiento estable se define en el protocolo.
    5.Participante que utilice remedios a base de hierbas,naturopáticos,tradicionales chinos,ayurvédicos o suplementos nutricionales o marihuana medicinal es elegible si es aceptado por el investigador.
    6.Participantes que se hayan sometido a esplenectomía deben haberse sometido a la resección al menos 3 mesesanstes de selección y estar vacunados según calendario anual de inmunización recomendado para adultos del Centro para el Control y la Prevención de Enfermedades de los Estados Unidos O estar vacunados según las directrices específicas del país o la normativa local.
    7.Tener suficiente acceso venoso para permitir la administración del fármaco mediante infusión y la extracción de muestras de sangre según el protocolo.
    8.Se recomienda estar al día con todas las vacunas adecuadas para la edad antes de la selección según las directrices médicas locales habituales.
    9.Hombre o mujer (de acuerdo con sus órganos y funciones reproductoras asignadas por el complemento cromosómico).
    10.Una mujer con capacidad de concebir debe tener un resultado negativo en una prueba de embarazo en suero altamente sensible en la selección y un resultado negativo en una prueba de embarazo en orina el día 1 antes de la administración de la intervención del estudio.
    11.Una mujer debe:
    a.No estar en edad fértil
    b.Estar en edad fértil y utilizar un método anticonceptivo altamente eficaz, preferiblemente independiente del usuario y aceptar seguir utilizando un método altamente eficaz mientras recibe la intervención del estudio y hasta 60 días después de la última dosis, el final de la exposición sistémica pertinente. El investigador deberá evaluar el potencial de fracaso del método anticonceptivo en relación con la primera dosis de la intervención del estudio.
    12.Una mujer debe aceptar no donar óvulos (ovocitos) ni congelarlos para su uso futuro con fines de reproducción asistida durante el estudio y durante un periodo de 30 días después de la administración de la intervención del estudio.
    13.Un participante varón sexualmente activo con una mujer con capacidad de concebir que no se haya sometido a una vasectomía debe aceptar el uso de un método anticonceptivo de barrera (p. ej., o bien un preservativo [con espuma/gel/película/crema/supositorio espermicida si está disponible en su zona] o una pareja con un capuchón oclusivo [diafragma o capuchón cervical] más espuma/gel/película/crema/supositorio espermicida si está disponible en su zona), durante el estudio y durante al menos 90 días después de recibir la última administración de la intervención del estudio.
    14.Un participante varón debe aceptar no donar semen para fines de reproducción durante el estudio y durante un mínimo de 90 días después de recibir la última administración de la intervención del estudio.
    15.Debe firmar un FCI que indique que el participante entiende el propósito y los procedimientos requeridos para el estudio y que está dispuesto a participar voluntariamente en el estudio y cumplir con todos los procedimientos del estudio.
    16.Debe ser capaz de leer y escribir.
    FASE EXTENSION ABIERTA
    Los participantes que hayan completado la fase doble ciego controlada con placebo de 24 semanas son aptos para entrar en la fase de EA.
    Los participantes que interrumpieran la intervención del estudio por un motivo distinto a la necesidad de hospitalización o tratamiento de rescate (IgIV, plasmaféresis) y que completaran el calendario de evaluaciones para toda la fase doble ciego controlada con placebo de 24 semanas pueden participar en la EA según el criterio del investigador.
    Los participantes afectados por la interrupción del estudio MOM-M281-005 debido a la pandemia de COVID 19 deben cumplir los siguientes criterios de inclusión:
    1.El investigador ha confirmado que el participante no está recibiendo, o no ha recibido desde la interrupción del estudio en fase II, ningún medicamento que pudiera poner en riesgo al participante cuando reciba nipocalimab o que pudiera interferir en la evaluación de la seguridad de nipocalimab
    2.Punto de inclusión aleatorizada 6.
    3.Punto de inclusión aleatorizada 7
    4.Se recomienda estar al día con todas las vacunas adecuadas para la edad antes de la selección según las directrices médicas locales habituales.
    5.Requisitos sexuales y anticonceptivos/de barrera según se describe en los criterios de inclusión de la fase doble ciego controlada con placebo n.º 9, 10, 11, 12, 13 y 14 anteriores.
    6.Punto de inclusión aleatorizada 15
    E.4Principal exclusion criteria
    1. Has a history of severe and/or uncontrolled liver, gastrointestinal, renal, pulmonary, cardiovascular, psychiatric, neurological or musculoskeletal disorder, hypertension, etc. that, might interfere with the patient’s participation or might jeopardize the safety of the participant.
    2. Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her gMG, or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant.
    3. Has MGFA Class I disease or presence of MG crisis (MGFA Class V) at screening, history of MG crisis within 1 month of screening, or fixed weakness (and/or ‘burnt out’ MG).
    4. Is dependent on gastric tube for nutritional needs or is ventilator-dependent.
    5. Is actively undergoing radiation or chemotherapy for an unresected thymoma/malignant thymoma.
    6. Has had a thymectomy within 12 months prior to screening, or thymectomy is planned during the study.
    7. Has current or a history of any neurologic disorder other than MG that might interfere with the accuracy of study assessments.
    8. Currently has a malignancy or has a history of malignancy within 3 years before screening.
    9. Has known allergies, hypersensitivity, or intolerance to nipocalimab or its excipients (refer to the IB).
    10. Has shown a previous severe immediate hypersensitivity reaction, such as anaphylaxis to therapeutic proteins (eg, monoclonal antibodies).
    11. Has experienced myocardial infarction, unstable ischemic heart disease, or stroke within 12 weeks of screening.
    12. Is planning to father a child while enrolled in this study or donate sperm within 90 days after the last administration of IMP.
    13. Is currently breastfeeding, pregnant, planning pregnancy, or egg donation during the study or within 30 days after the last dose of IMP.
    14. History of moderate or severe substance or alcohol use
    15. Is currently taking IgG Fc-related protein therapeutics, or Fc-conjugated therapeutic agents, including factor or enzyme replacement.
    16. Has received, rituximab within 6 months prior to first administration of IMP, except for returning Phase 2 participants.
    17. Has received a live vaccine within 3 months prior to screening or needing live vaccine during the study, or within at least 3 months after the last administration of IMP. Participants are allowed to receive SARS-CoV-2 vaccine, unless it is a live vaccine.
    18. Has received plasmapheresis, immunoadsorption therapy, or IVIg within 6 weeks prior to baseline.
    19. Has another medical condition that requires corticosteroids unless the dose has been stable for at least 4 weeks prior to baseline and is expected to remain stable during the study.
    20. Has another medical condition that requires an immunosuppressive agent unless the medication has been used for at least 6 months, the dose has been stable for at least 3 months prior to baseline and the medication and the dose are expected to remain stable during the study.
    21. Has previously received nipocalimab. (Not applicable to returning Phase 2 participants)
    22. Is receiving or has received an investigational intervention (including investigational vaccines) within 3 months or 5 half-lives (whichever is longer) or used an invasive investigational medical device within 3 months before the planned first dose administration of IMP.
    23. Has a severe infection including opportunistic infections requiring parenteral anti-infectives and/or hospitalization, and/or is assessed as serious/clinically significant by the investigator, within 8 weeks prior to screening. The participant may be rescreened after the 8-week exclusionary period has passed.
    24. Has a chronic infection or requires chronic treatment with anti-infectives.
    25. Tests positive for hepatitis B virus infection
    26. Is seropositive for antibodies to hepatitis C virus unless they satisfy 1 of the following conditions listed in the protocol.
    27. History of being human immunodeficiency virus (HIV)1 or HIV2 antibody-positive, or tests positive for HIV at screening.
    28. COVID-19 infection or contact with infected persons as per the protocol
    29. Has current suicidal ideation evidenced by a “yes” response to Questions 4 or 5 in the C-SSRS at screening or baseline, or a history of suicidal ideation/behavior in the past year prior to screening.
    30. Had major surgery within 3 months before screening, or will not have fully recovered from surgery, or has surgery planned during the time of participation in the study.
    31. Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments.
    32. Is an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.
    1.Antecedentes de trastornos hepáticos,gastrointestinales,renales,pulmonares,cardiovasculares,psiquiátricos,neurológicos o musculoesqueléticos graves y/o no controlados,hipertensión u otroque pueda interferir en participación o seguridad del paciente
    2.Tener cualquier síndrome de inmunodeficiencia clínica confirmado/sospechado no relacionado con el tratamiento de MGg,o antecedentes familiares de inmunodeficiencia congénita o hereditaria,salvo se confirme que no están presentes en el participante
    3.Enfermedad de clase I según la MGFA o presencia de crisis de MG (clase V según la MGFA) en selección,antecedentes de crisis MG el mes anterior a selección o debilidad fija (y/o MG de “desgaste”)
    4.Depende de tubo gástrico para necesidades nutricionales o de un respirador
    5.Está sometido radioterapia/quimioterapia para timoma/timoma maligno no resecado
    6.Timectomía en los 12 meses anteriores a selección,o prevision de timectomía durante el estudio.
    7.Presenta o tiene antecedentes de trastorno neurológico distinto de MG que interfieras en precisión de evaluaciones del estudio
    8.Presenta neoplasia maligna o antecedentes en los 3 años anteriores a selección
    9.Alergia,hipersensibilidad o intolerancia a nipocalimab o sus excipientes(consultar el MI)
    10.Ha mostrado anteriormente reacción de hipersensibilidad inmediata grave,como anafilaxia a proteínas terapéuticas(p.ej.,anticuerpos monoclonales)
    11.Infarto de miocardio,cardiopatía isquémica inestable o accidente cerebrovascular en las 12 semanas previas a selección
    12.Tiene previsto engendrar un hijo durante el estudio o donar esperma en los 90 días posteriores a última dosis del medicamento en estudio
    13.Está en periodo de lactancia,embarazada,intención de quedarse embarazada o donar óvulos durante el estudio o en 30 días posteriores a última dosis del medicamento en estudio
    14.Antecedentes de trastorno por consumo de sustancias o alcohol moderado o grave
    15.Tratamientos con proteínas Fc de la IgG o agentes terapéuticos conjugados con Fc,incluido reemplazo de factores o enzimas
    16.Ha recibido rituximab en los 6 meses anteriores a primera administración-medicamento en estudio
    17.Ha recibido una vacuna-microorganismos vivos en los 3 meses anteriores a selección o necesidad conocida de recibirla durante el estudio,o en los 3 meses posteriores a última administración-medicamento en estudio.Se permite recibir la vacuna de SARS-CoV-2,a menos que sea vacuna con microorganismos vivos
    18.Ha recibido plasmaféresis,inmunoadsorción o IgIV en las 6 semanas previas al inicio.
    19.Otra afección médica que requiere corticoesteroides salvo dosis estable al menos 4 semanas antes del inicio del estudio
    20.Otra afección médica que requiere inmunodepresor,salvo que se haya utilizado al menos 6 meses en dosis estable 3 meses antes de inicio y plan de medicamento y dosis estables durante el estudio
    21.Ha recibido previamente nipocalimab.No se aplica a participantes procedentes del estudio en fase II
    22.Ha recibido intervención en investigación (incluidas vacunas en investigación) en los 3 meses o 5 semividas anteriores (lo que sea más largo)o utilizado un producto médico invasivo en investigación en los 3 meses anteriores a administración de la primera dosis del estudio
    23.Infección grave,incluidas infecciones oportunistas que requiere antiinfecciosos parenterales y/u hospitalización,y/o que el investigador considera grave/clínicamente significativa,en las 8 semanas previas a la selección.El participante puede volver a ser re-seleccionado una vez transcurrido el periodo de exclusión de 8 semanas.
    24.Tiene una infección crónica o requiere tratamiento crónico con antiinfecciosos
    25.Resultado positivo de infección por el virus hepatitis B
    26.Es seropositivo para anticuerpos contra el virus hepatitis C (VHC), a menos que cumpla 1 las condiciones listadas en el protocolo
    27.Antecedentes positivos de anticuerpos contra el virus de la inmunodeficiencia humana (VIH)1 o VIH2 o resultado positivo para VIH en la selección.
    28.Infección por COVID-19 o contact con personas infectadas según protocolo
    29.Tiene pensamientos suicidas demostrados por respuesta afirmativa a las preguntas 4 o 5 de la escala C-SSRS en la selección o al inicio, o antecedentes de pensamientos/comportamientos suicidas en el último año antes de la selección
    30.Se ha sometido a cirugía mayor en los 3 meses anteriores a la selección, o no se ha recuperado completamente de la cirugía, o tiene programada una cirugía durante el estudio
    31.Presenta cualquier enfermedad que, en opinión del investigador, haga que participar no sea lo mejor para el paciente o pueda impedir,limitar o confundir las evaluaciones especificadas en el protocolo
    32.Es un empleado del investigador o del centro del estudio,con participación directa en el estudio propuesto u otros estudios bajo la dirección de dicho investigador o centro del estudio, o es familiar de los empleados o del investigador.
    E.5 End points
    E.5.1Primary end point(s)
    Average change from baseline (screening and Day 1) in MG-ADL total score over Weeks 22, 23 and 24.
    Cambio promedio desde el inicio (seleccion ydía 1) en la puntuación total de MG-ADL durante las semanas 22, 23 y 24.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Throughout the double-blind phase of the study.
    Durante toda la fase de doble ciego del estudio.
    E.5.2Secondary end point(s)
    1. The average change in the QMG score over Weeks 22 and 24. Analyzed using a similar method (appropriate for the region) as for the primary efficacy endpoint, but since the QMG is not assessed at Week 23, the contrast will average the change from baseline over Weeks 22 and 24 of the double-blind placebo-controlled phase.
    2. Percentage of participants whose average MG-ADL total score over weeks 22, 23 and 24 of the double blind, placebo-controlled phase is at least a 2-point improvement compared to baseline. The average score for a participant is the average of the non-missing values at Weeks 22, 23 and 24. A participant must have a non-missing value at Week 24 and at least 1 non-missing value at Week 22 or 23 in order to have a non-missing average score. A participant with a missing average score will be considered a nonresponder. Analyzed by Cochran-Mantel-Haenszel test controlling for the baseline MG-ADL total score randomization strata (≤9, >9), autoantibody status, and region.
    3. Loading dose response, defined for each participant as improvement in the MG-ADL total ≥2 points at Week 1 and/or Week 2. A participant with a missing assessment at either time point will be considered a nonresponder at that time point. Analyzed by Cochran-Mantel-Haenszel test controlling for the baseline MG-ADL total score randomization strata (≤9, >9), autoantibody status, and region.
    4. Symptom remission, defined as the average percentage of participants with MG-ADL score of 0 or 1 over weeks 22, 23 and 24 of the double-blind, placebo-controlled phase. Analyzed with a repeated measures logistic regression model employing a similar contrast as for the primary efficacy analysis.
    5. Sustainability of therapeutic response, defined as the percentage of participants with improvement in MG-ADL total score of ≥ 2 points at Week 2 sustained through Week 24, with no more than 2 excursions allowed at Weeks 3 through 23 (excursions defined as loss of improvement in MG-ADL score of ≥ 2 points). A participant with a missing assessment at a time point will be considered a nonresponder at that time point. Analyzed by Cochran-Mantel-Haenszel test controlling for the baseline MG-ADL total score randomization strata (≤9, >9), autoantibody status, and region.
    1.Cambio medion en la puntuación de QMG en las semanas 22y 24. Analizado utilizando un método similar (apropiado para la región) al criterio de valoración principal de eficacia, pero dado que el QMG no se evalúa en la semana 23, el contraste promediará el cambio desde el valor inicial durante las semanas 22 y 24 del estudio doble ciego controlado con placebo. fase.
    2.porcentaje de participantes cuya mejora media en la puntuación total de AVD-MG a lo largo de las semanas 22, 23 y 24 de la fase doble ciego controlada con placebo es una mejora de al menos 2 puntos en comparación con el valor inicial. la puntacion promedio de un participante es el promedio de los valores que no faltan en las semanas 22, 23 y 24. Un participante debe tener un valor que no falte en la semana 24 y al menos 1 valor que no falte en la semana 22 o 23 para tener un puntaje promedio que no falte. Un participante con puntuacion promedio faltante será considerado un no respondedor. Analizado mediante la prueba de Cochran-Mantel-Haenszel que controla los estratos de aleatorización de puntuación total de MG-ADL basales (≤9,> 9), el estado de autoanticuerpos y la región.
    3.Respuesta a la dosis de carga, definida para cada participante com la mejora en la puntuación total de AVD-MG de ≥2 puntos en la semana 1 y/o la semana 2. Un participante con una evaluación faltante en cualquier momento se considerará que no responde en ese momento. Analizado mediante la prueba de Cochran-Mantel-Haenszel que controla los estratos de aleatorización de puntuación total de MG-ADL basales (≤9,> 9), el estado de autoanticuerpos y la región
    4.Remisión de los síntomas, definido como orcentaje medio de participantes con una puntuación de 0 o 1 en AVD-MG a lo largo de las semanas 22, 23 y 24 de la fase doble ciego controlada con placebo. Analizado con un modelo de regresión logística de medidas repetidas empleando un contraste similar al del análisis primario de eficacia.
    5. Sostenibilidad de la respuesta terapéutica, definido como porcentaje de participantes con una mejora en la puntuación total de AVD-MG de ≥2 puntos en la semana 2 hasta la semana 24 de la fase doble ciego controlada con placebo, con no más de 2 desviaciones permitidas en las semanas 3 a 23 (la desviación se define como una pérdida de mejora en la puntuación de AVD-MG de ≥2 puntos).Un participante al que le falte una evaluación en un momento determinado se considerará no respondedor en ese momento. Analizado mediante la prueba de Cochran-Mantel-Haenszel que controla los estratos de aleatorización de puntuación total de MG-ADL basales (≤9,> 9), el estado de autoanticuerpos y la región.
    E.5.2.1Timepoint(s) of evaluation of this end point
    - QMG score over Weeks 22 and 24.
    - MG-ADL total score over weeks 22, 23 and 24
    - Loading dose response at Week 1 and/or Week 2.
    - Symptom remission over weeks 22, 23 and 24
    - Sustainability of therapeutic response Week 2 through Week 24
    Puntuación QMG durante las semanas 22 y 24.
    - Puntuación total de MG-ADL durante las semanas 22, 23 y 24
    - Respuesta a la dosis de carga en la semana 1 y / o la semana 2.
    - Remisión de síntomas en las semanas 22, 23 y 24
    - Sostenibilidad de la respuesta terapéutica desde la semana 2 hasta la semana 24
    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 No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Fase aleatorizada, doble ciega, controlada por plabebo seguida de una fase the extension abierta
    Randomized, double blind, placebo controlled phase followed by an Open Label extension phase.
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    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 concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA49
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Belgium
    Canada
    China
    Colombia
    Czechia
    Denmark
    France
    Germany
    Hungary
    Italy
    Japan
    Korea, Republic of
    Mexico
    Poland
    Russian Federation
    Spain
    Sweden
    Taiwan
    Turkey
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of study is considered as the last visit for the last participant in the study.
    El fin del estudio es considerado la ultima visita del último paciente del estudio
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days11
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days22
    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: 113
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 67
    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 state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 75
    F.4.2.2In the whole clinical trial 105
    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 who complete the double-blind placebo-controlled phase will continue to the OLE phase where treatment with nipocalimab will continue until 2 years after marketing authorization in a participant’s local country or until nipocalimab becomes available commercially or via other continued access program, whichever comes first. After that no further treatment and medical supervision of the patients after the end of the clinical trial is planned for the above clinical trial.
    Los participantes que completen fase doble ciego controlada por placebo continuarán a fase OLE continuando con tratamiento de nipocalimab hasta 2 años después de autorización de comercialización en el país del participante o hasta que nipocalimab esté disponible comercialmente o mediante otro programa de acceso continuo, lo que ocurra primero. Después, no se planea ningún tratamiento adicional ni supervisión médica de pacientes tras finalización del ensayo clínico.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Ancillare Europe LTD
    G.4.3.4Network Country Netherlands
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-09-03
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-08-09
    P. End of Trial
    P.End of Trial StatusOngoing
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