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    Summary
    EudraCT Number:2019-000330-19
    Sponsor's Protocol Code Number:64407564MMY1002
    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:2019-07-26
    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 number2019-000330-19
    A.3Full title of the trial
    A Phase 1b Study of Subcutaneous Daratumumab Regimens in Combination with Bispecific T Cell Redirection Antibodies for the Treatment of Subjects with Multiple Myeloma
    Estudio fase 1b de regímenes de daratumumab subcutáneo en combinación con anticuerpos biespecíficos de redirección de los células T para el tratamiento de sujetos con mieloma múltiple.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Clinical Study of Subcutaneous Daratumumab Regimens in Combination with Bispecific T Cell Redirection Antibodies for the Treatment of Subjects with Multiple Myeloma
    Estudio clínico de regímenes de daratumab subcutáneo en combinación con anticuerpos de redirección de células T biespecíficos para el tratamiento de sujetos con mieloma múltiple.
    A.4.1Sponsor's protocol code number64407564MMY1002
    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 NV
    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 SA
    B.5.2Functional name of contact pointGlobal Clinical Operations Spain
    B.5.3 Address:
    B.5.3.1Street AddressPº de las Doce Estrellas 5-7
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28042
    B.5.3.4CountrySpain
    B.5.4Telephone number+34 647309 073
    B.5.5Fax number+34 91 7228628
    B.5.6E-mailIsoriano@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 nameJNJ-64007957
    D.3.2Product code JNJ-64007957
    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 INNNot Assigned
    D.3.9.2Current sponsor codeJNJ-64007957
    D.3.9.3Other descriptive nameJNJ-64007957-AAA
    D.3.9.4EV Substance CodeSUB185866
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeHumananized I IgG4 bispecific antibody against BCMA and CD3
    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 nameVehicle 001
    D.3.2Product code Vehicle 001
    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 INNRECOMBINANT HUMAN ALBUMIN
    D.3.9.3Other descriptive nameRECOMBINANT HUMAN ALBUMIN SOLUTION
    D.3.9.4EV Substance CodeSUB185529
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.2
    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: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation 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 nameJNJ-64407564
    D.3.2Product code JNJ-64407564
    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 INNJNJ-64407564
    D.3.9.2Current sponsor codeJNJ-64407564
    D.3.9.3Other descriptive nameJNJ-64407564-AAA
    D.3.9.4EV Substance CodeSUB190574
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typea Humanized DuoBody® Antibody
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/13/1153
    D.3 Description of the IMP
    D.3.1Product nameDaratumumab co-formulated with recombinant human hyaluronidase (rHuPH20)
    D.3.2Product code JNJ-54767414
    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 INNDARATUMUMAB
    D.3.9.1CAS number 945721-28-8
    D.3.9.2Current sponsor codeJNJ-54767414
    D.3.9.3Other descriptive nameHUMAX-CD38
    D.3.9.4EV Substance CodeSUB175772
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number120
    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
    Multiple myeloma
    Mieloma múltiple
    E.1.1.1Medical condition in easily understood language
    Bone marrow cancer
    Cáncer de médula ósea
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10028228
    E.1.2Term Multiple myeloma
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objectives are:
    ● Part 1: To identify recommended Phase 2 doses and schedules (RP2Ds) for each combination
    ● Part 2: To characterize the safety of each RP2D for each combination
    Los objetivos principales son:
    ● Parte 1: Identificar las dosis y pautas recomendadas de la Fase 2 (RP2D) para cada combinación
    ● Parte 2: Caracterizar la seguridad de cada RP2D para cada combinación
    E.2.2Secondary objectives of the trial
    The secondary objectives are:
    ● To characterize the pharmacokinetics and pharmacodynamics of each study treatment
    ● To assess the immunogenicity of each study treatment
    ● To evaluate the antitumor activity of each combination
    Los objetivos secundarios son:
    ● Caracterizar la farmacocinética y farmacodinámica de cada tratamiento de estudio.
    ● Evaluar la inmunogenicidad de cada tratamiento de estudio
    ● Evaluar la actividad antitumoral de cada combinación
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Each potential subject must satisfy all of the following criteria to be enrolled in the study:
    1. ≥18 years of age.
    2. Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
    3. Must have either of the following:
    ● Received at least 3 prior lines of therapy (see definition below) including a PI (≥2 cycles or 2 months of treatment) and an IMiD (≥2 cycles or 2 months of treatment) in any order during the treatment (except for subjects who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months).
    OR
    ● Disease that is double refractory to a PI and an IMiD. For subjects who have received more than 1 type of PI, the disease must be refractory to the most recent one. Similarly, for those who have received more than 1 type of IMID, the disease must be refractory to the most recent one.
    4. Measurable disease at Screening as defined by any of the following:
    ● Serum M-protein level ≥1.0 g/dL (in non-IgG myeloma, an M-protein level ≥0.5 g/dL);or
    ● Urine M-protein level ≥200 mg/24 hours; or
    ● Light chain multiple myeloma: Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.
    5. Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at Screening and at Cycle 1, Day 1 predose.
    6. Clinical lab values as stated in the protocol
    7. Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (βhuman chorionic gonadotropin [β-hCG]) or urine.
    8. Women must be:
    a. Not of childbearing potential b. Of childbearing potential and
    – Practicing a highly effective, preferably user-independent method of contraception (failure rate of <1% per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study drug and until 100 days after last dose.
    – Agree to pregnancy testing (serum or urine) within 100 days after the last study drug administration.
    A woman using oral contraceptives must use an additional contraceptive method in addition to the requirements listed above.
    9. Men must wear a condom when engaging in any activity that allows for passage of ejaculate to another person, during the study and for 100 days after the last dose of study drug. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak.
    10. Women must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 100 days after the last dose of study drug.
    11. Men must agree not to donate sperm for the purpose of reproduction during the study and for at least 100 days after receiving the last dose of study drug.
    12. Sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and is willing to and able to participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the subject’s disease.
    13. Willing and able to adhere to the prohibitions and restrictions specified in this protocol.

    Definition:
    • A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of steroids (ie, less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days) would not be considered prior lines of therapy.

    For complete inclusion criteria, please refer page no:32 of the protocol.
    Cada sujeto potencial debe satisfacer todos los siguientes criterios para ser inscrito en el estudio:
    1. ≥18 años de edad.
    2. Diagnóstico inicial documentado del mieloma múltiple según los criterios de diagnóstico del International Myeloma Working Group (IMWG).
    3. Debe tener cualquiera de las siguientes características:
    ● Heber recibido al menos 3 líneas de terapia previas (ver definición a continuación) incluyendo un IP (≥2 ciclos o 2 meses de tratamiento) y un IMiD (≥2 ciclos o 2 meses de tratamiento) en cualquier orden durante el tratamiento (excepto para los sujetos que discontinuaron cualquiera de estos tratamientos debido a una reacción alérgica severa dentro de los primeros 2 ciclos/meses).
    O
    ● Enfermedad que es doblemente refractaria a un IP y a un IMiD. Para los sujetos que han recibido más de un tipo de IP, la enfermedad debe ser refractaria a la más reciente. De manera similar, para aquellos que han recibido más de un tipo de IMID, la enfermedad debe ser refractaria a la más reciente.
    4. Enfermedad medible en el momento de la evaluación, tal como se define en cualquiera de los siguientes términos:
    ● Nivel de proteína M en suero ≥1.0 g/dL (en el mieloma no IgG, un nivel de proteína M ≥0.5 g/dL); o
    ● Nivel de proteína M en orina ≥200 mg/24 horas; o
    ● Mieloma múltiple de cadena ligera: Cadena ligera libre de inmunoglobulina en suero ≥10 mg/dL e inmunoglobulina en suero anormal kappa lambda free light chain ratio.
    5. Eastern Cooperative Oncology Group (ECOG) calificación de desempeño de 0 o 1 en el cribado y en la predosis del ciclo 1, día 1.
    6. Valores de laboratorio clínico según lo establecido en el protocolo
    7. Las mujeres en edad fértil deben someterse a una prueba de embarazo negativa en el momento del cribado y antes de la primera dosis del medicamento en estudio, utilizando una prueba de embarazo altamente sensible, ya sea en suero (βhuman chorionic gonadotropin[β-hCG]) u orina.
    8. En caso de ser mujer:
    a. No ser fértil
    b. Ser fértil y
    –Practicar un método anticonceptivo de alta eficacia, preferiblemente independiente del usuario (tasa de fallo de <1 % por año cuando se usa de manera constante y correcta) y aceptar seguir utilizándolo mientras reciba el fármaco del estudio y hasta 100 días después de la última dosis.
    –Aceptar la realización de una prueba de embarazo (suero u orina) en los 100 días siguientes a la última administración del fármaco del estudio.
    Una mujer que utilice anticonceptivos orales debe emplear un método anticonceptivo adicional, además de los requisitos mencionados anteriormente.
    9. Los hombres deben utilizar un preservativo al realizar cualquier actividad que permita el paso del esperma eyaculado a otra persona durante el estudio y durante 100 días después de la última dosis del fármaco del estudio. Los participantes varones también deben ser informados de que su pareja femenina debe usar un método anticonceptivo de alta eficacia, ya que el preservativo podría romperse o tener fugas.
    10. Las mujeres deben comprometerse a no donar óvulos (óvulos, ovocitos) para fines de reproducción asistida durante el estudio y durante al menos 100 días después de la última dosis del medicamento en estudio.
    11. Los hombres deben comprometerse a no donar esperma con fines de reproducción durante el estudio y durante al menos 100 días después de recibir la última dosis del medicamento en estudio.
    12. Firmar un documento de consentimiento informado (ICF) indicando que él o ella entiende el propósito y los procedimientos requeridos para el estudio y que está dispuesto y capacitado para participar en el estudio. Se debe obtener el consentimiento antes de iniciar cualquier prueba o procedimiento relacionado con el estudio que no sea parte del estándar de atención para la enfermedad del sujeto.
    13. Estar dispuesto y ser capaz de adherirse a las prohibiciones y restricciones especificadas en este protocolo.

    Definición:
    - Una sola línea de terapia puede consistir en uno o más agentes, y puede incluir inducción, trasplante de células madre hematopoyéticas y terapia de mantenimiento. La radioterapia, el bifosfonato o un solo ciclo corto de esteroides (es decir, menos o igual al equivalente de 40 mg/día de dexametasona durante 4 días) no se considerarían líneas de tratamiento previas.

    Para conocer los criterios de inclusión completos, consulte la página nº 32 del protocolo.
    E.4Principal exclusion criteria
    Any potential participant who meets any of the following criteria will be excluded from participating in the study:
    1. Treatment in the prior 3 months with an anti-CD38 therapy (eg, daratumumab), or discontinuation of a prior anti-CD38 therapy at any time due to an adverse event related to the anti-CD38 therapy.
    2. Prior antitumor therapy as follows, before the first dose of study drug:
    • Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive medical device within 21 days or at least 5 half-lives, whichever is less.
    • Monoclonal antibody treatment within 21 days (anti-CD38 treatment cannot be used within the prior 3 months
    • Cytotoxic therapy within 21 days.
    • PI therapy within 14 days.
    • IMiD therapy within 7 days.
    • Radiotherapy within 21 days. However, if the radiation portal covered ≤5% of the bone marrow reserve, the subject is eligible irrespective of the end date of radiotherapy.
    • Gene modified adoptive cell therapy (eg, chimeric antigen receptor modified Tcells, NK cells) within 3 months
    3. A cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within the 14-day period before the first dose of study drugs
    4. Live, attenuated vaccine within 4 weeks prior to the first dose of study drug.
    5. Toxicity from previous anticancer therapy that has not resolved to baseline levels or to Grade ≤1 (except alopecia or peripheral neuropathy).
    6. Stem cell transplantation:
    • Allogeneic stem cell transplantation ≤6 months before the first dose of study drug.
    • Active graft-versus-host disease.
    • Autologous stem cell transplantation ≤12 weeks before the first dose of study drug.
    • An immunosuppressive drug (eg, cyclosporine, tacrolimus) within 28 days before the first dose of study drug.
    7. Central nervous system involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, whole body magnetic resonance imaging (MRI) and lumbar cytology are required.
    8. Active plasma cell leukemia (>2.0 x 10^9/L plasma cells by standard differential), Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or AL amyloidosis.
    9. Seropositive for human immunodeficiency virus.
    10. Seropositive for hepatitis B (defined by a positive test for hepatitisB surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HbsAg negative but positive for antibodies to hepatitis B core antigen [Anti-HBc] and/or antibodies to hepatitis B surface antigen [Anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (Anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
    11. Seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy).
    12. Either of the following:
    • Chronic obstructive pulmonary disease (COPD) with forced expiratory volume in 1 second (FEV1) <50% of predicted normal. NOTE: FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 is <50% of predicted normal.
    • Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. NOTE: subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study.
    13. Allergies, hypersensitivity, or intolerance to any study intervention or its excipients (refer to Investigator’s Brochures).
    14. Any serious underlying medical condition, such as:
    • Evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection
    • Active autoimmune disease or a history of autoimmune disease.
    • Psychiatric conditions (eg, alcohol or drug abuse), severe dementia, or altered mental status
    • Any other issue that would impair the ability of the subject to receive or tolerate the planned treatment at the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject(eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

    For complete exclusion criteria, please refer page no:29 of the protocol.
    Cualquier participante potencial que cumpla cualquiera de los siguientes criterios será excluido:
    1. Tratamiento en los últimos 3 meses con una terapia anti-CD38 (p.e., daratumumumab), o interrupción de una terapia anti-CD38 anterior en cualquier momento debido a un evento adverso relacionado con la terapia anti-CD38.
    2. Terapia antitumoral previa de la siguiente manera, antes de la primera dosis del medicamento en estudio:
    - Terapia dirigida, terapia epigenética o tratamiento con un medicamento en investigación o un dispositivo médico invasivo dentro de los 21 días o al menos 5 semividas, lo que sea menor.
    - Tratamiento con anticuerpos monoclonales dentro de los 21 días (el tratamiento anti-CD38 no se puede utilizar dentro de los 3 meses anteriores)
    - Terapia citotóxica en 21 días. - Terapia de IP dentro de los 14 días.
    - Terapia IMiD dentro de 7 días. - Radioterapia dentro de los 21 días. Sin embargo, si el portal de radiación cubre el ≤5% de la reserva de médula ósea, el sujeto es elegible independientemente de la fecha de finalización de la radioterapia. - Terapia celular adoptiva modificada genéticamente en un plazo de 3 meses
    3. Una dosis acumulada de corticosteroides equivalente a ≥140 mg de prednisona dentro del período de 14 días antes de la primera dosis de los medicamentos en estudio.
    4. Vacuna viva atenuada dentro de las 4 semanas anteriores a la primera dosis del medicamento en estudio.
    5. Toxicidad por terapia anticancerosa previa que no se ha resuelto a los niveles de referencia o al Grado ≤1 (excepto alopecia o neuropatía periférica).
    6. Trasplante de células madre:
    - Trasplante alogénico de células madre ≤6 meses antes de la primera dosis del medicamento en estudio. - Enfermedad activa de injerto contra huésped. - Trasplante autólogo de células madre ≤12 semanas antes de la primera dosis del medicamento en estudio. - Un medicamento inmunosupresor dentro de los 28 días anteriores a la primera dosis del medicamento en estudio.
    7. Afectación del sistema nervioso central o presenta signos clínicos de afectación meníngea del mieloma múltiple. Si se sospecha de cualquiera de los dos, se requieren imágenes por resonancia magnética (IRM) de todo el cuerpo y citología lumbar.
    8. Leucemia de células plasmáticas activas (>2.0 x 10^9/L por diferencial estándar), macroglobulinemia de Waldenström, síndrome POEMS (polineuropatía, organomegalia, endocrinopatía, proteína M y cambios cutáneos) o amiloidosis AL.
    9. Seropositivo para el virus de inmunodeficiencia humana.
    10. Seropositivo para hepatitis B (definido por una prueba positiva para el antígeno de superficie de la hepatitis B[HBsAg]). Los sujetos con infección resuelta deben ser examinados utilizando la medición en tiempo real de los niveles de ADN del virus de la hepatitis B (VHB) mediante reacción en cadena de la polimerasa (PCR). Aquellos que sean positivos a la PCR serán excluidos. EXCEPCIÓN: Los sujetos con hallazgos serológicos que sugieran la vacunación contra el VHB (positividad anti-HBs como único marcador serológico) Y un historial conocido de vacunación previa contra el VHB, no necesitan ser sometidos a pruebas de ADN del VHB por PCR.
    11. Seropositivo para hepatitis C (excepto en el contexto de una respuesta virológica sostenida[SVR], definida como aviremia al menos 12 semanas después de la finalización de la terapia antiviral).
    12. Cualquiera de los siguientes:
    - Enfermedad pulmonar obstructiva crónica (EPOC) con volumen espiratorio forzado en 1 segundo (VEF1) <50% de lo normal previsto. NOTA: Se requiere la prueba de FEV1 para los sujetos sospechosos de tener EPOC y los sujetos deben ser excluidos si el FEV1 es <50% de lo normal predicho.
    - Asma moderada o severa persistente dentro de los últimos 2 años, o asma no controlada de cualquier clasificación. NOTA: los sujetos que actualmente han controlado el asma intermitente o el asma leve persistente controlada pueden participar en el estudio.
    13. Alergias, hipersensibilidad o intolerancia a cualquier intervención del estudio o sus excipientes (consulte los folletos del investigador).
    14. Cualquier condición médica subyacente grave, como:
    - Evidencia de infección viral, bacteriana o fúngica sistémica grave, activa o no controlada.
    - Enfermedad autoinmune activa o antecedentes de enfermedad autoinmune.
    - Afecciones psiquiátricas
    - Cualquier otro asunto que pudiera perjudicar la capacidad del sujeto para recibir o tolerar el tratamiento planeado en el sitio de la investigación, para entender el consentimiento informado o cualquier condición por la cual, en la opinión del investigador, la participación no sería en el mejor interés del sujeto (p.e., comprometer el bienestar) o que pudiera prevenir, limitar o confundir las evaluaciones especificadas en el protocolo.
    Consultar pág 29 del protocolo
    E.5 End points
    E.5.1Primary end point(s)
    1. Frequency and severity of dose-limiting toxicities
    2. Frequency and severity of adverse events and serious adverse events
    1. Frecuencia y gravedad de las toxicidades que limitan la dosis
    2. Frecuencia y gravedad de los eventos adversos y de los eventos adversos graves
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Cycle 1 (28 days)
    2. From the time of signing the ICF till 100 days after the last dose of study drug or until the start of subsequent systemic anticancer therapy, if earlier.
    1. Ciclo 1 (28 días)
    2. Desde el momento de la firma de la HIP hasta 100 días después de la última dosis del medicamento en estudio o hasta el inicio de la posterior terapia sistémica contra el cáncer, si es anterior.
    E.5.2Secondary end point(s)
    1. Serum concentrations and pharmacodynamic markers
    2. Presence of anti-drug antibodies
    3. Overall response rate
    4. Clinical benefit rate (minimal response or better)
    5. Duration of and time to response
    1. Concentraciones séricas y marcadores farmacodinámicos
    2. Presencia de anticuerpos antifármaco.
    3. Tasa de respuesta general
    4. Tasa de beneficio clínico (respuesta mínima o mejor)
    5. Duración y tiempo de respuesta
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Serum concentrations- Predose, Day (D) 1 of each cycle, End of treatment (EOT), follow-up
    Pharmacodynamic markers- Part 1: Cycle (C) 1 D1, C1D9, C1D10, C1D11, C1D12, C1D15, C1D16, C1D22, C2D1, C3D1,C7D1
    Pharmacodynamic markers- Part 2: C1D1, C1D9, C1D11, C1D15
    2. Part 1 and Part 2 (Serum and Plasma): C1D1, C2D1, C4D1, C7D1, EOT, Post-treatment follow-up
    3. Duration of the study
    4. Duration of the study
    5. Duration of the study
    1. Concentraciones séricas - Predosis, Día (D) 1 de cada ciclo, Fin del tratamiento (EOT), seguimiento
    Marcadores farmacodinámicos - Parte 1: Ciclo (C) 1 D1, C1D9, C1D10, C1D11, C1D12, C1D15, C1D16, C1D22, C2D1, C3D1,C7D1
    Marcadores farmacodinámicos - Parte 2: C1D1, C1D9, C1D11, C1D15
    2. Parte 1 y Parte 2 (Suero y Plasma): C1D1, C2D1, C4D1, C7D1, EOT, Seguimiento post-tratamiento
    3. Duración del estudio
    4. Duración del estudio
    5. Duración del estudio
    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 Yes
    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
    Immunogenecity and biomarker assessment
    Inmunogeneidad y evaluación de biomarcadores
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Dose escalation and dose expansion study
    Estudio de escalada y expansión de dosis
    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 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 Yes
    E.8.1.7.1Other trial design description
    Estudio multi-cohorte
    multi-cohort study
    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 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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA9
    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
    Netherlands
    Spain
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    Última visita del útlimo 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 months1
    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 months1
    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: 80
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 20
    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 state14
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 23
    F.4.2.2In the whole clinical trial 100
    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)
    standard of care
    estándar de atención
    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 Decision2019-09-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-09-16
    P. End of Trial
    P.End of Trial StatusOngoing
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