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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   42771   clinical trials with a EudraCT protocol, of which   7044   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
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    EudraCT Number:2017-000538-78
    Sponsor's Protocol Code Number:INCB39110-301
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2017-07-31
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2017-000538-78
    A.3Full title of the trial
    A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Itacitinib or Placebo in Combination With Corticosteroids for the Treatment of First-Line Acute Graft Versus-Host Disease
    GRAVITAS-301: Estudio de fase III randomizado, doble ciego y controlado con placebo, de itacitinib o placebo en combinación con corticosteroides para el tratamiento de primera línea de la enfermedad de injerto contra huésped en fase aguda.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study evaluating safety and efficacy of Itacitinib or Placebo in combination with corticosteroids for the treatment of first-line acute graft versus-host disease
    Un estudio que evalúa la seguridad y eficacia de Itacitinib o placebo en combinación con corticosteroides para el tratamiento de primera línea de la enfermedad de injerto contra huésped en fase aguda.
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code numberINCB39110-301
    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 Trial 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+34658271136
    B.5.5Fax number13024252734
    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 nameItacitinib
    D.3.2Product code INCB039110
    D.3.4Pharmaceutical form Modified-release 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.3.9.1CAS number 1334302-63-4
    D.3.9.2Current sponsor codeINCB039110 ADIPATE
    D.3.9.3Other descriptive nameITACITINIB ADIPATE
    D.3.9.4EV Substance CodeSUB184194
    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. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. 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.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Male or female, 18 years of age or older who have received an allogeneic hematopoietic stem cell transplant (allo-HSCT) and have developed Grade II to IV acute GVHD
    Varones o mujeres, de 18 años en adelante que hayan recibido un alotrasplante de células madre hematopoyéticas (ATCMH) y hayan presentado EICHa de grado II a IV
    E.1.1.1Medical condition in easily understood language
    Acute graft versus host disease after allogeneic stem cell transplantation
    Enfermedad de injerto contra huésped en fase aguda tras el trasplante alogénico de células madre
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10066260
    E.1.2Term Acute graft versus host disease
    E.1.2System Organ Class 10021428 - Immune system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10066262
    E.1.2Term Acute graft versus host disease in skin
    E.1.2System Organ Class 10021428 - Immune system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10066264
    E.1.2Term Acute graft versus host disease in intestine
    E.1.2System Organ Class 10021428 - Immune system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10066263
    E.1.2Term Acute graft versus host disease in liver
    E.1.2System Organ Class 10021428 - Immune 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
    Compare the efficacy of itacitinib in combination with corticosteroids versus placebo in combination with corticosteroids in terms of overall response rate (ORR) at Day 28 in subjects with acute graft-versus-host disease (aGVHD).
    Comparar la eficacia de itacitinib en combinación con corticosteroides frente a placebo en combinación con corticosteroides en lo que respecta a la tasa de respuesta global (TRG) el día 28 en sujetos con enfermedad de injerto contra huésped en fase aguda (EICHa).
    E.2.2Secondary objectives of the trial
    - Compare the efficacy between treatment cohorts at a subsequent key clinical landmark (key secondary objective).
    - Compare additional response and longer-term efficacy outcomes between treatment cohorts.
    - Assess the incidence and severity of adverse events (AEs) and serious adverse events.
    - Evaluate the pharmacokinetics of itacitinib when administered in combination with corticosteroids.
    - Evaluate the incidence of secondary graft failure.
    - Evaluate the use and discontinuation of corticosteroids.
    - Evaluate the use and discontinuation of immunosuppressive medications.
    - Evaluate the incidence of aGVHD flares.
    - Evaluate the incidence of cGVHD.
    - Comparar la eficacia entre las cohortes de tratamiento en un momento clínico clave posterior.
    - Comparar variables de eficacia a largo plazo y de respuesta adicionales entre las opciones de tratamiento.
    - Evaluar la incidencia e intensidad de los acontecimientos adversos (AA) y los acontecimientos adversos graves.
    - Evaluar la farmacocinética de itacitinib cuando se administra en combinación con corticosteroides.
    - Evaluar la incidencia de fracaso secundario del injerto.
    - Evaluar el uso y la suspensión del tratamiento con corticosteroides.
    - Evaluar el uso y la suspensión del tratamiento con inmunosupresores.
    - Evaluar la incidencia de brotes de la EICHa.
    - Evaluar la incidencia de EICHc.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Male or female, 18 years of age or older.
    • Has undergone 1 allo-HSCT from any donor (related or unrelated with
    any degree of HLA matching) and any donor source (bone marrow, peripheral blood stem cells, or cord blood) for a hematologic malignancy or disorder. Recipients of myeloablative and reduced-intensity conditioning regimens are eligible.
    • Clinically suspected Grade II to IV aGVHD as per MAGIC criteria, occurring after allo-HSCT and any GVHD prophylaxis regimen. Biopsies should be obtained to pathologically confirm aGVHD; in cases where a biopsy is negative, is unable to be obtained, or is clinically contraindicated, clinical suspicion of aGVHD by the treating physician is sufficient, provided that alternative diagnoses of drug effects or infection are adequately ruled out.
    • Evidence of myeloid engraftment (eg, absolute neutrophil count ≥ 0.5 × 109/L for 3 consecutive days if ablative therapy was previously used). Use of growth factor supplementation is allowed.
    • Varones o mujeres, de 18 años en adelante.
    • Haber recibido un ATCMH de cualquier donante (emparentado o no emparentado, con cualquier grado de histocompatibilidad) y cualquier fuente donante (médula ósea, células madre de sangre periférica o cordón umbilical) para un trastorno o neoplasia maligna hematológicos. Son elegibles los receptores de regímenes de acondicionamiento mieloablativo y de intensidad reducida.
    • Sospecha clínica de EICHa de grado II a IV según los criterios MAGIC con posterioridad al ATCMH y cualquier tratamiento profiláctico contra la EICH. Deben realizarse biopsias para la confirmación anatomopatológica de la EICHa; cuando la biopsia indique que no hay EICH, no pueda realizarse o esté contraindicada clínicamente, la sospecha clínica de EICHa por el médico responsable del tratamiento será suficiente, siempre que se descarten adecuadamente diagnósticos alternativos de efectos farmacológicos o infección.
    • Signos de prendimiento mieloide del injerto (p. ej., recuento absoluto de neutrófilos ≥0,5 × 109/l durante tres días consecutivos si se usó previamente tratamiento mieloablativo). Se permite el uso de factores de crecimiento de forma complementaria.
    E.4Principal exclusion criteria
    • Has received more than 1 allo-HSCT.
    • Has received more than 2 days of systemic corticosteroids for acute-GVHD.
    • Presence of GVHD overlap syndrome.
    • Presence of an active uncontrolled infection.
    • Haber recibido más de un ATCMH.
    • Haber recibido corticosteroides sistémicos durante más de 2 días contra la EICHa.
    • Presencia de síndrome de superposición relativo a la EICH.
    • Presencia de una infección activa y no controlada.
    E.5 End points
    E.5.1Primary end point(s)
    ORR at Day 28, defined as the proportion of subjects demonstrating a complete response (CR), very good partial response (VGPR), or partial response (PR).
    TRG el día 28, definida como el porcentaje de sujetos que demuestran respuesta completa (RC), respuesta parcial muy buena (RPMB) o respuesta parcial (RP).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Day 28
    Día 28
    E.5.2Secondary end point(s)
    - NRM at Month 6, defined as the proportion of subjects who died due to causes other than malignancy relapse at Month 6 (key secondary endpoint).
    - ORR, defined as the proportion of subjects demonstrating a CR, VGPR, or PR at Days 14, 56, and 100.
    - NRM at Months 9, 12, and 24.
    - Duration of response, defined as the interval from first response until graft-versus-host disease (GVHD) progression or death.
    - Time to response, defined as the interval from treatment initiation to first response.
    - Malignancy relapse rate, defined as the proportion of subjects whose underlying malignancy relapses.
    - Malignancy relapse-related mortality rate, defined as the proportion of subjects whose malignancy relapses and has a fatal outcome.
    - Failure-free survival, defined as the proportion of subjects who are still alive, have not relapsed, have not required additional therapy for aGVHD, and have not demonstrated signs or symptoms of chronic graft-versus-host disease (cGVHD), at Month 6.
    - Overall survival (OS), defined as the interval from study enrollment to death due to any cause.
    - Clinical safety data (eg, AEs, infections) will be tabulated and listed.
    - Cmax, Cmin, tmax, AUC, and CL/F.
    - Incidence rate of secondary graft failure, defined as > 95% recipient cells any time after engraftment with no signs of relapse, OR retransplantation because of secondary neutropenia (< 0.5 × 109/L) and/or thrombocytopenia (< 20 × 109/L) within 2 months of transplant.
    - Average and cumulative corticosteroid dose at Days 28, 56, 100, and 180; proportion of subjects who discontinue corticosteroids at Days 56 and 100.
    - Proportion of subjects who discontinue immunosuppressive medications at Days 56 and 100.
    - Incidence rate of aGVHD flares through Day 100.
    - Incidence rate of cGVHD at Days 180 and 365.
    - Mortalidad sin recidiva (MSR) en el mes 6, definida como el porcentaje de sujetos que fallecen por causas distintas de una recidiva de la neoplasia maligna en el sexto mes.
    - TRG, definida como el porcentaje de sujetos que demuestran RC, RPMB o RP los días 14, 56 y 100.
    - MSR en los meses 9, 12 y 24.
    - Tiempo transcurrido hasta la respuesta, definida como el intervalo transcurrido desde la instauración de la respuesta hasta la primera respuesta.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Day 14, 28, 56, 100
    Months 6, 9, 12 and 24
    Día 14, 28, 56, 100
    Meses 6, 9, 12 and 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 Yes
    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 Yes
    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. 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 No
    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 concerned15
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA45
    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
    Korea, Republic of
    New Zealand
    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 study will end once 75% of subjects have achieved 2-year transplant-related mortality, have died, or have been lost to follow-up.

    An end of the trial can not be determined as each subject enrolled in the study may continue to receive study treatment as long as benefit is being observed and/or treatment withdrawal criteria are not met.
    El estudio terminará cuando el 75 % de los sujetos haya alcanzado la mortalidad a los 2 años relacionada con el trasplante, haya fallecido o se haya perdido el contacto con ellos durante el seguimiento.

    No se puede determinar el final del ensayo, ya que cada sujeto inscrito en el estudio puede seguir recibiendo tratamiento del estudio mientras se observe el beneficio y / o no se cumplan los criterios de retirada del tratamiento.
    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 days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 393
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 43
    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 200
    F.4.2.2In the whole clinical trial 439
    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)
    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 Decision2017-07-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-07-14
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2020-07-13
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