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    Summary
    EudraCT Number:2018-004076-35
    Sponsor's Protocol Code Number:INCB01158-206
    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:2019-06-11
    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 number2018-004076-35
    A.3Full title of the trial
    A Randomized Open-Label Phase 1/2 Study of INCB001158 Combined With Subcutaneous (SC) Daratumumab, Compared to Daratumumab SC, in Participants With Relapsed or Refractory Multiple Myeloma
    Estudio Fase I/II, aleatorizado y abierto, de INCB001158 combinado con Daratumumab Subcutáneo (SC) en comparación con Daratumumab (SC) en pacientes con Mieloma Múltiple Refractario o en Recaída
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Randomized Open-Label Phase 1/2 Study of INCB001158 Combined With Subcutaneous (SC) Daratumumab, Compared to Daratumumab SC, in Participants With Relapsed or Refractory Multiple Myeloma
    Estudio Fase I/II, aleatorizado y abierto, de INCB001158 combinado con Daratumumab Subcutáneo (SC) en comparación con Daratumumab (SC) en pacientes con Mieloma Múltiple Refractario o en Recaída
    A.4.1Sponsor's protocol code numberINCB01158-206
    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 SponsorIncyte Corporation
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportIncyte Corporation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIncyte Corporation
    B.5.2Functional name of contact pointClinical Trials Information
    B.5.3 Address:
    B.5.3.1Street Address1801 Augustine Cut-Off
    B.5.3.2Town/ cityWilmington
    B.5.3.3Post codeDE 19803
    B.5.3.4CountryUnited States
    B.5.4Telephone number+34961622798
    B.5.5Fax number+34961246201734
    B.5.6E-mailanagarciaferia@gmail.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 nameNot yet available
    D.3.2Product code INCB001158 25 mg
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot yet available
    D.3.9.2Current sponsor codeINCB001158
    D.3.9.3Other descriptive nameINCB001158
    D.3.9.4EV Substance CodeSUB189023
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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 No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.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 nameNot available yet
    D.3.2Product code INCB001158 100 mg
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot yet available
    D.3.9.2Current sponsor codeINCB001158
    D.3.9.3Other descriptive nameINCB001158
    D.3.9.4EV Substance CodeSUB189023
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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 No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.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 nameDaratumumab SC
    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 namedaratumumab SC
    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
    Relapsed or Refractory Multiple myeloma
    Mieloma Múltiple Refractario o en Recaída
    E.1.1.1Medical condition in easily understood language
    Relapsed or Refractory Multiple myeloma
    Mieloma Múltiple Refractario o en Recaída
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    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
    Phase 1: To determine the safety, tolerability, and RP2D of INCB001158 in combination with daratumumab SC.

    Phase 2: To compare the ORR of the RP2D of INCB001158 in combination with daratumumab SC to daratumumab SC monotherapy.
    Fase 1: determinar la seguridad, la tolerabilidad y la DRF2 de INCB001158 en combinación con daratumumab s.c.
    Fase 2: comparar la TRO de la DRF2 de INCB001158 en combinación con daratumumab s.c. con daratumumab s.c. en monoterapia.
    E.2.2Secondary objectives of the trial
    Phase 1: To determine the efficacy of INCB001158 in combination with daratumumab SC.

    Phase 2: To determine the safety and tolerability of INCB001158 monotherapy at RP2D, and to compare the safety and tolerability and RP2D of INCB001158 in combination with daratumumab SC to daratumumab SC monotherapy.
    Fase 1: determinar la eficacia de INCB001158 en combinación con daratumumab s.c.
    Fase 2: determinar la seguridad y la tolerabilidad de INCB001158 en monoterapia en la DRF2 y comparar la seguridad, tolerabilidad y la DRF2 de INCB001158 en combinación con daratumumab s.c. con daratumumab s.c. en monoterapia.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Ability to comprehend and willingness to sign a written ICF for the study.
    2. Men or women aged 18 years or older.
    3. Prior diagnosis of MM according to IMWG diagnostic criteria.
    4. Has measurable disease at screening, as defined by the following:
    • Serum M-protein level ≥ 1.0 g/dL, or
    • Urine M-protein level ≥ 200 mg/24 hours, or
    • Serum Ig FLC ≥ 10 mg/dL and abnormal serum Ig kappa to lambda FLC ratio.
    5. Has received at least 3 prior lines (including PI, IMiD, and anti-CD38 therapies) but not more than 5 prior lines of MM treatment.
    a. Has received last dose of prior anti-CD38 therapy at least 3 months before initiation of study treatment.
    b. Has achieved a response (MR or better), based on investigator’s evaluation of response by IMWG criteria, to prior anti-CD38 therapy.
    c. Has documented evidence of PD as defined by the IMWG criteria on or after their last regimen.
    6. ECOG performance status of 0 or 1.
    7. Willing to avoid pregnancy or fathering children based on the criteria below:
    a. Woman of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 51 years of age).
    b. Woman of childbearing potential who has a negative serum pregnancy test at screening and before the first dose on Day 1 and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening until 3 months after the last dose of the last component of study treatment and must refrain from donating eggs (ova, oocytes). Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participant and their understanding confirmed.
    c. Man who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening until 3 months after the last dose of the last component of study treatment and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participant and their understanding confirmed.
    8. Willing to provide fresh and archival bone marrow aspiration and biopsy tissue during screening and on study.
    1.Capacidad para comprender y voluntad de firmar un CI por escrito para el estudio.
    2.Hombres o mujeres de 18 años de edad o mayores.
    3.Diagnóstico previo de MM, de acuerdo con los criterios diagnósticos del IMWG (Rajkumar et al 2014).
    4.Tener enfermedad medible en el momento de la selección, según se define a continuación:
    •Nivel de proteína M en suero ≥ 1,0 g/dl, o
    •Nivel de proteína M en orina ≥ 200 mg/24 horas, o
    •CLL de Ig en suero ≥ 10 mg/dl y cociente de CLL de Ig kappa y lambda en suero anormal.
    5.Haber recibido al menos 3 líneas anteriores de tratamiento (incluyendo PI, IMiD, tratamientos anti-CD38) pero no más de 5 líneas anteriores de tratamiento MM.
    a.Haber recibido la última dosis del anterior tratamiento anti-CD38 al menos 3 meses antes del inicio del tratamiento del estudio.
    b.Haber logrado una respuesta (RM o mejor) con el anterior tratamiento anti-CD38, según la evaluación de la respuesta efectuada por del investigador atendiendo a los criterios del IMWG.
    c.Tener indicios documentados de PE, según la definición de los criterios del IMWG con o después del último régimen de tratamiento.
    6.Estado general de 0 a 1 según el ECOG.
    7.Tener voluntad de evitar embarazos o engendrar hijos en función de los criterios que aparecen a continuación:
    a.Mujeres que no se encuentren en edad fértil (es decir, esterilizadas quirúrgicamente mediante histerectomía u ovariectomía bilateral O ≥ 12 meses de amenorrea y edad mínima de 51 años).
    b.Mujeres en edad fértil que tienen una prueba de embarazo en suero con resultado negativo en la selección y antes de la primera dosis del día 1 y que acceden a tomar las precauciones oportunas para evitar embarazos (con una fiabilidad mínima del 99 %) desde la selección hasta 3 meses después de la última dosis del último componente del tratamiento del estudio y que se deben abstener de donar óvulos. Se deben comunicar a los participantes los métodos permitidos con una eficacia mínima del 99 % en la prevención del embarazo y confirmarse su comprensión.
    c.Los hombres que accedan a tomar las precauciones oportunas para evitar engendrar hijos (con una fiabilidad mínima del 99 %) desde la selección hasta 3 meses después de la última dosis del último componente del tratamiento del estudio y que deben abstenerse de donar semen durante este período. Se deben comunicar a los participantes los métodos permitidos con una eficacia mínima del 99 % en la prevención del embarazo y confirmarse su comprensión.
    8.Tener voluntad de proporcionar tejido de biopsia y aspirado de médula ósea frescos y de archivo durante la selección y durante el estudio.
    E.4Principal exclusion criteria
    1. Receipt of any of the following treatment within the indicated interval before the first administration of study drug:
    a. Anti-myeloma treatment within 2 weeks or 5 half-lives (whichever is longer).
    − Exception: Washout of immune checkpoint inhibitor therapy is NOT required.
    b. Investigational drug (including investigational vaccines) or invasive investigational medical device within 4 weeks.
    c. Autologous stem cell transplant within 12 weeks, or allogeneic stem cell transplant at any time.
    d. Plasmapheresis within 4 weeks.
    e. Radiation therapy within 2 weeks.
    f. Major surgery within 2 weeks, or inadequate recovery from an earlier surgery, or surgery planned during the time the participant is expected to participate in the study or within 2 weeks after the last dose of study treatment.
    2. Toxicity ≥ Grade 2 from previous anti-myeloma therapy except for stable chronic toxicities (≤ Grade 2) not expected to resolve, such as stable Grade 2 peripheral neuropathy.
    3. Known additional malignancy (other than MM) that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the participant has been disease-free for > 1 year, after treatment with curative intent.
    4. Known meningeal involvement of MM.
    5. Participants with laboratory values at screening defined in the protocol (Table 10).
    6. Significant concurrent, uncontrolled medical condition, including but not limited to the following:
    a. Known COPD (defined as a FEV1 < 50% of predicted normal), persistent asthma, or history of asthma within the past 2 years. Participants with known or suspected COPD or asthma must have a FEV1 test during screening.
    b. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
    c. Acute diffuse infiltrative pulmonary disease.
    d. Clinically significant or uncontrolled cardiac disease, including the following:
    − Unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, and arrhythmia requiring therapy unless approved by medical monitor.
    − History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful. A screening QTcF interval > 470 ms is excluded.
    e. Inability of the participant to swallow and retain oral medication.
    7. Any of the following:
    a. Known to be seropositive for hepatitis B (defined by a positive test for HBsAg). Participants with resolved infection (ie, participants who are HBsAg-negative but positive for antibodies to anti-HBc and/or anti-HBs) must be screened using real-time PCR measurement of HBV DNA levels. Those who are PCR-positive will be excluded.
    − Exception: Participants 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.
    b. Known to be seropositive for hepatitis C. Participants who have had definitive treatment for HCV are permitted if HCV RNA is undetectable at screening visit.
    c. Known to be seropositive for HIV. HIV testing is not required unless mandated by the local health authority.
    8. Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome, or amyloidosis.
    9. Prior treatment with an arginase inhibitor for any indication.
    10. Known or suspected defect in the function of the urea cycle, including a known deficiency of carbamoyl phosphate synthetase I, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinate lyase, N-acetyl glutamate synthetase, or arginase.
    11. Current use of any prohibited medication as described in Protocol Section 6.8.2.
    12. Known hypersensitivity or severe reaction to INCB001158, daratumumab, hyluronidase, monoclonal antibodies, human proteins, or their excipients (refer to INCB001158 IB, daratumumab IB, and Hylenex® Prescribing Information).
    13. Women who are pregnant or breastfeeding.
    14. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
    1.Recepción de cualquiera de los sig .tratam.s dentro del intervalo indicado antes de la primera admin. del fármaco del estudio:
    a. Tratam. contra el mieloma en un plazo de 2 semanas o 5 semividas
    Excepción: NO es necesario reposo farmacológico del tratam. con inhibidores de punto de control inmunitario.
    b.Fármaco en investigación (incluidas vacunas en investigación) o dispositivo médico en investig. para una técnica invasiva en el plazo de 4 semanas.
    c.Autotrasplante de células madre en el plazo de 12 semanas o alotrasplante de células madre en cualquier moment.
    d.Plasmaféresis en el plazo de 4 semanas.
    e.Radioterapia en el plazo de 2 sem.
    f.Cirugía mayor en el plazo de 2 sem. Recuper. inadecuada de cirugía anterior o cirugía prevista durante el tiempo q. se prevé q. participe el sujeto en el estudio o en un plazo de 2 semanas después de la última dosis del tratam.del estudio.
    2.Toxicidad de grado ≥ 2 de un tratam. previo contra el mieloma excepto para toxicidades crónicas estables (grado ≤ 2) q.no se prevé q. se resuelvan, tales como neuropatía periférica estable de grado 2.
    3.Otra neoplasia maligna conocida (distinta de MM) en progresión o q.requiera un tratam. activo, o antecedentes de otra neoplasia maligna en los 2 años anteriores a la entrada en el estudio, salvo carcinoma basocelular o carcinoma epidermoide de la piel curados, cáncer de vejiga superficial, neoplasia intraepitelial prostática, carcinoma localizado del cuello uterino, otras neoplasias malignas no invasivas o inactivas, o tumores sin presencia de enfermedad durante > 1 año tras el tratam. con intención curativa.
    4.Afectación meníngea conocida por MM.
    5. Participantes con valores de laboratorio en la selección definidos en el protocolo (Tabla 10).
    6. Condición médica significativa, concurrente e incontrolada, q.incluye pero no se limita a lo siguiente:
    a. EPOC conocida (definida como un FEV1 <50% del normal previsto), asma persistente o antecedentes de asma en los últimos 2 años. Los participantes con EPOC o asma conocidos o sospechosos deben realizarse una prueba de FEV1 durante la prueba de detección.
    b. Enfermedad infecciosa activa crónica o actual q. requiere antibióticos sistémicos, antifúngicos o tratam. antiviral.
    c. Enfermedad pulmonar infiltrativa difusa aguda.
    d. Enfermedad cardíaca clínicamente significativa o no controlada, q. incluye lo siguiente:
    -Angina inestable, infarto agudo de miocardio dentro de los 6 meses posteriores al día 1 a partir de la administración del medicamento del estudio, insuficiencia cardíaca congestiva de clase III o IV de la New York Heart Association y arritmia q. requiera terapia, a menos q. el monitor médico lo apruebe.
    -Historia o presencia de un ECG anormal q., en opinión del invest., es clínicamente significativo. Se excluye un intervalo QTcF de cribado> 470 ms.
    e. Incapacidad del participante para tragar y retener la medicación oral.
    7. Cualquiera de los siguientes:
    a. Seropositivo para la hepatitis B (definido por una prueba positiva para HBsAg). Los participantes con infección resuelta (es decir, los participantes q. son HBsAg negativos pero positivos para anticuerpos contra anti-HBc y / o anti-HBs) deben examinarse utilizando una medición de PCR en tiempo real de los niveles de ADN del VHB. Quienes sean PCR-positivos serán excluidos.
    - Excepción: articipantes con hallazgos serológicos q. sugieran vacunación contra el VHB (Y una hist. conocida de vacunación previa contra el VHB no necesitan ser examinados para det.el ADN del VHB por PCR.
    b. Se sabe q. son seropositivos para la hepatitis C. Se permite a los participantes q. hayan recibido un tratam. definitivo para el VHC si el ARN del VHC no es detectable en la visita de selección.
    c. Conocido por ser seropositivo para el VIH. La prueba de VIH no se requiere a menos q. sea req.rido por la autoridad de salud local.
    8. Leucemia de células plasmáticas, macroglobulinemia de Waldenström, síndrome de POEMS o amiloidosis.
    9. Tratam. previo con un inhibidor de la arginasa para cualquier indicación.
    10. Defecto conocido o sospechado en la función del ciclo de la urea, q. incluye una deficiencia conocida de la carbamoil fosfato sintetasa I, ornitina transcarbamilasa, argininosuccinato sintetasa, argininosuccinato liasa, N-acetil glutamato sintetasa o arginasa.
    11. Uso actual de cualquier medicam. phibido como se describe en la Sección 6.8.2.
    12. Hipersensibilidad conocida o reacción grave a INCB001158, daratumumab, hyluronidase, anticuerpos monoclonales, proteínas humanas o sus excipientes
    13. Mujeres embarazadas o en periodo de lactancia.
    14. Cualquier condición q., a juicio del invest., interfiriera con la participación total en el estudio, incluida la administración del tratam. del estudio y la asistencia a las visitas requeridas; suponen un riesgo significativo para el participante; o interferir con la interpretación de los datos del estudio.
    E.5 End points
    E.5.1Primary end point(s)
    Phase 1: Safety and tolerability determined by monitoring the frequency, duration, and severity of AEs.

    Phase 2: ORR, defined as the proportion of participants with a documented response PR or better, as per IMWG criteria.
    Fase 1:Seguridad y tolerabilidad determinadas mediante la monitorización de la frecuencia, la duración y la intensidad de los AA.
    Fase 2: TRO, definida como la proporción de participantes con una respuesta documentada RP o mejor, según los criterios IMWG.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Safety will be monitored continuously.
    Efficacy/disease evaluations will be performed at each treatment cycle as specified in the schedule of activity.
    La seguridad será monitoreada continuamente.
    Las evaluaciones de eficacia / enfermedad se realizarán en cada ciclo de tratamiento como se especifica en el programa de actividades
    E.5.2Secondary end point(s)
    Phase 1: ORR, defined as the proportion of participants with a documented response PR or better, as per IMWG criteria.

    Phase 2: Safety and tolerability determined by monitoring the frequency, duration, and severity of AEs.
    Fase1:TRO, definida como la proporción de participantes con una respuesta documentada RP o mejor, según los criterios IMWG.
    Fase2: Seguridad y tolerabilidad determinadas mediante la monitorización de la frecuencia, la duración y la intensidad de los AA.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Safety will be monitored continuously.
    Efficacy/disease evaluations will be performed at each treatment cycle as specified in the schedule of activity.
    La seguridad será monitoreada continuamente.
    Las evaluaciones de eficacia / enfermedad se realizarán en cada ciclo de tratamiento como se especifica en el programa de actividades
    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 Yes
    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) 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 Yes
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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 EEA10
    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
    Germany
    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 último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months9
    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: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 78
    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 state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 58
    F.4.2.2In the whole clinical trial 98
    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)
    None (subjects may receive treatment as long as they are deriving benefit, tolerating the regimen and do not meet any of the withdrawal criteria)
    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 Decision2019-08-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-05-21
    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
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