Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   43207   clinical trials with a EudraCT protocol, of which   7151   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.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2021-002211-65
    Sponsor's Protocol Code Number:GIS-2021-JAKihemo
    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:2021-06-11
    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 number2021-002211-65
    A.3Full title of the trial
    EFFECT OF TOFACITINIB ON COAGULATION AND PLATELET FUNCTION, AND ITS ROLE IN THROMBOEMBOLIC EVENTS
    EFECTO DE TOFACITINIB SOBRE LA COAGULACIÓN Y FUNCIÓN PLAQUETARIA, Y SU PAPEL EN LOS EVENTOS TROMBOEMBÓLICOS
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    EFFECT OF TOFACITINIB ON COAGULATION
    EFECTO DE TOFACITINIB SOBRE LA COAGULACIÓN
    A.4.1Sponsor's protocol code numberGIS-2021-JAKihemo
    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 SponsorFundación Española de Gastroenterología
    B.1.3.4CountrySpain
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportpfizer
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationHopsital Universitario de La Princesa
    B.5.2Functional name of contact pointSandra Hermida Vázquez
    B.5.3 Address:
    B.5.3.1Street AddressC/ Diego de León, 62, 3ª planta
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28006
    B.5.3.4CountrySpain
    B.5.4Telephone number+34913093911
    B.5.6E-mailsandra.hermida.hlp@gmail.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.1.1Trade name Adalimumab
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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.3.4Pharmaceutical form 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 INNADALIMUMAB
    D.3.9.1CAS number 331731-18-1
    D.3.9.4EV Substance CodeSUB20016
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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 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 RoleComparator
    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 Yes
    D.2.1.1.1Trade name Infliximab
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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.3.4Pharmaceutical form 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 INNINFLIXIMAB
    D.3.9.1CAS number 170277-31-3
    D.3.9.4EV Substance CodeSUB02681MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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 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 RoleComparator
    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 Yes
    D.2.1.1.1Trade name Golimumab
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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.3.4Pharmaceutical form 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 INNGOLIMUMAB
    D.3.9.1CAS number 476181-74-5
    D.3.9.4EV Substance CodeSUB25638
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number50 to 100
    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 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: 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 Yes
    D.2.1.1.1Trade name Tofacitinib
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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.3.4Pharmaceutical form Pastille
    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 INNTOFACITINIB
    D.3.9.1CAS number 477600-75-2
    D.3.9.4EV Substance CodeSUB33104
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number10 to 20
    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 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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    ulcerative colitis
    colitis ulcerosa
    E.1.1.1Medical condition in easily understood language
    ulcerative colitis
    colitis ulcerosa
    E.1.1.2Therapeutic area Body processes [G] - Biological Phenomena [G16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10045365
    E.1.2Term Ulcerative colitis
    E.1.2System Organ Class 100000004856
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10009790
    E.1.2Term Coagulation time
    E.1.2System Organ Class 10022891 - Investigations
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10061684
    E.1.2Term Platelet function test
    E.1.2System Organ Class 10022891 - Investigations
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - To study the ex vivo effect of tofacitinib on platelet function and coagulation in patients with UC.
    - Estudiar el efecto de tofacitinib sobre la función plaquetaria y coagulación en pacientes con colitis ulcerosa (CU) mediante un abordaje ex vivo.
    E.2.2Secondary objectives of the trial
    - To evaluate the in vivo effect of tofacitinib on the procoagulant status (platelet function and coagulation) in patients with UC over time.
    - To determine if there is a specific effect of tofacitinib on haemostasis in UC patients treated with this drug compared with biological agents for UC.
    - To generate a collection of biological samples (serum, plasma, nucleic acids, RNA, stool and urine) from a cohort of patients with UC (before and after
    treatment with tofacitinib or anti-TNFα) that can be used for future complementary studies.
    - Evaluar el efecto in vivo de tofacitinib sobre el estado procoagulante (función plaquetaria y coagulación) en pacientes con CU a lo largo del tiempo.
    - Determinar si hay un efecto específico de tofacitinib en la hemostasia de pacientes con CU tratados con este fármaco en comparación con los fármacos biológicos para la CU.
    - Crear un repositorio de muestras biológicas (suero, plasma, ácidos nucleicos, ARN, heces y orina) de una cohorte de pacientes con CU (antes y después del tratamiento con tofacitinib o un anti-TNFα) que será utilizado en futuros estudios complementarios.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    EX VIVO STUDY IN PATIENTS WITH UC

    PATIENTS WITH UC:
    - Over 18 years old.
    - Diagnosis of UC according to the criteria of the European Crohn’s and Colitis Organisation (ECCO).
    - Previous treatments are allowed, provided they have remained stable for the past 3 months.
    - In the case of patients with active UC, they should have endoscopic activity within 1 month of starting the treatment (Mayo endoscopic sub-index of ≥ 2).
    -Women of childbearing potential who use methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include:
    intrauterine device (IUD)
    bilateral tubal occlusion
    vasectomised partner
    sexual abstinence

    Or women of childbearing potential who use a combination of male condom with either cap, diaphragm or sponge with spermicide


    INDIVIDUALS WITHOUT UC:
    - Over 18 years old.
    - Subjects not diagnosed with UC, or other inflammatory allergic, malignant or autoimmune diseases.
    - Women of childbearing potential who use methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include:
    intrauterine device (IUD)
    bilateral tubal occlusion
    vasectomised partner
    sexual abstinence

    Or women of childbearing potential who use a combination of male condom with either cap, diaphragm or sponge with spermicide

    IN VIVO STUDY IN PATIENTS WITH UC

    PATIENTS WITH UC:
    - Over 18 years old.
    - Diagnosis of UC according to the criteria of the European Crohn’s and Colitis Organisation (ECCO).
    - Have indication of treatment with anti-TNFα (infliximab, adalimumab or golimumab) o tofacitinib.
    - Be the first received JAK-inhibitor or anti-TNFα with a given mechanism of action and have endoscopic activity of UC within 1 month of starting the treatment (Mayo endoscopic sub-index of ≥ 2).
    - Previous treatments (including corticosteroids and immunosuppressants) are allowed provided that they have been stable for the last 3 months before beginning treatment with JAK-inhibitor or anti-TNFα and that they are maintained at a stable dose for the duration of the study
    -Women of childbearing potential who use methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include:
    intrauterine device (IUD)
    bilateral tubal occlusion
    vasectomised partner
    sexual abstinence

    Or women of childbearing potential who use a combination of male condom with either cap, diaphragm or sponge with spermicide


    INDIVIDUALS WITHOUT UC:
    - Over 18 years old.
    - Subjects not diagnosed with UC, or other inflammatory, allergic, malignant or autoimmune diseases.
    - Women of childbearing potential who use methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include:
    intrauterine device (IUD)
    bilateral tubal occlusion
    vasectomised partner
    sexual abstinence

    Or women of childbearing potential who use a combination of male condom with either cap, diaphragm or sponge with spermicide
    ESTUDIO EX VIVO EN PACIENTES CON CU

    PACIENTES CON CU:

    - Mayores de 18 años.
    - Diagnóstico de la CU según los criterios de la European Crohn’s and Colitis Organisation (ECCO).
    - Se permiten los tratamientos previos (incluyendo corticoesteroides e inmunosupresores) siempre que se hayan mantenido estables durante los últimos 3 meses.
    - En el caso de pacientes con CU activa, deben tener actividad endoscópica en el plazo de 1 mes desde el inicio del tratamiento (subíndice endoscópico de Mayo ≥ 2).
    - Mujeres en edad fértil que utilicen métodos anticonceptivos con un ratio de error <1% al año. Ejemplos de métodos anticonceptivos cuyo ratio de error es <1% al año son:
    1. Dispositivo intrauterino (DIU).
    2. Oclusión tubaria bilateral.
    3. Pareja con vasectomía.
    4. Abstinencia sexual.
    O mujeres en edad fértil que utilicen doble barrera anticonceptiva como puede ser una combinación de preservativo masculino con capuchón, diafragma o esponja con espermicida.

    Una mujer es considerada fértil a partir de la menarquía y hasta que alcanza la postmenopausia después de 12 meses de amenorrea espontánea. Siempre y cuando no haya sido sometida a alguna cirugía tal como: histerectomía, salpingectomía bilateral u ooferoctomía bilateral.



    PACIENTES SIN CU:

    - Mayores de 18 años.
    - Sujetos no diagnosticados de CU, ni de otras enfermedades inflamatorias, alérgicas, malignas o autoinmunes.
    - Mujeres en edad fértil que utilicen métodos anticonceptivos con un ratio de error <1% al año. Ejemplos de métodos anticonceptivos cuyo ratio de error es <1% al año son:
    1. Dispositivo intrauterino (DIU).
    2. Oclusión tubaria bilateral.
    3. Pareja con vasectomía.
    4. Abstinencia sexual.
    O mujeres en edad fértil que utilicen doble barrera anticonceptiva como puede ser una combinación de preservativo masculino con capuchón, diafragma o esponja con espermicida.

    Una mujer es considerada fértil a partir de la menarquía y hasta que alcanza la postmenopausia después de 12 meses de amenorrea espontánea. Siempre y cuando no haya sido sometida a alguna cirugía tal como: histerectomía, salpingectomía bilateral u ooferoctomía bilateral.



    ESTUDIO IN VIVO EN PACIENTES CON CU

    PACIENTES CON CU:

    - Mayores de 18 años.
    - Diagnóstico de la CU según los criterios de la European Crohn’s and Colitis Organisation (ECCO).
    - Tener indicación de tratamiento con anti-TNFα (infliximab, adalimumab o golimumab) o tofacitinib.
    - Ser el primer inhibidor de JAK o anti-TNFα recibido con un mecanismo de acción determinado; tener actividad endoscópica de la CU en el plazo de 1 mes desde el inicio del tratamiento (subíndice endoscópico de Mayo de ≥ 2).
    - Mujeres en edad fértil que utilicen métodos anticonceptivos con un ratio de error <1% al año. Ejemplos de métodos anticonceptivos cuyo ratio de error es <1% al año son:
    1. Dispositivo intrauterino (DIU).
    2. Oclusión tubaria bilateral.
    3. Pareja con vasectomía.
    4. Abstinencia sexual.
    O mujeres en edad fértil que utilicen doble barrera anticonceptiva como puede ser una combinación de preservativo masculino con capuchón, diafragma o esponja con espermicida.

    Una mujer es considerada fértil a partir de la menarquía y hasta que alcanza la postmenopausia después de 12 meses de amenorrea espontánea. Siempre y cuando no haya sido sometida a alguna cirugía tal como: histerectomía, salpingectomía bilateral u ooferoctomía bilateral.


    PACIENTES SIN CU:

    - Mayores de 18 años.
    - Sujetos no diagnosticados de CU, ni de otras enfermedades inflamatorias, alérgicas, malignas o autoinmunes.
    - Mujeres en edad fértil que utilicen métodos anticonceptivos con un ratio de error <1% al año. Ejemplos de métodos anticonceptivos cuyo ratio de error es <1% al año son:

    1. Dispositivo intrauterino (DIU).
    2. Oclusión tubaria bilateral.
    3. Pareja con vasectomía.
    4. Abstinencia sexual.
    O mujeres en edad fértil que utilicen doble barrera anticonceptiva como puede ser una combinación de preservativo masculino con capuchón, diafragma o esponja con espermicida.

    Una mujer es considerada fértil a partir de la menarquía y hasta que alcanza la postmenopausia después de 12 meses de amenorrea espontánea. Siempre y cuando no haya sido sometida a alguna cirugía tal como: histerectomía, salpingectomía bilateral u ooferoctomía bilateral.
    E.4Principal exclusion criteria
    EX VIVO STUDY IN PATIENTS WITH UC

    PATIENTS WITH UC:
    - Under 18 years old.
    - Immune-mediated disease, neoplasm or active infection.
    - Pregnancy or lactation.
    - Alcohol or drug abuse.
    - Ostomy.
    - Abdominal surgery in the last 6 months.
    - Colectomy.
    - Active infection with hepatitis B, C or HIV virus.
    - Medical history of thromboembolic events.
    -Treatment with anticoagulants, antiplatelets or other drugs that alter the coagulation.
    - Use of combined hormonal contraceptives or hormone replacement therapy.
    - Hereditary coagulation disorders.
    - Refusal to give consent for participation in the study.

    INDIVIDUALS WITHOUT UC:
    - Under 18 years of age.
    - Advanced chronic disease or any other pathology that prevents the monitoring of the protocol of this study.
    - Pregnancy or lactation.
    - Alcohol or drug abuse.
    - Ostomy.
    - Abdominal surgery in the last 6 months.
    - Colectomy.
    - Active infection with hepatitis B, C or HIV virus.
    - Medical history of thromboembolic events.
    -Treatment with anticoagulants, antiplatelets or other drugs that alter the coagulation.
    - Use of combined hormonal contraceptives or hormone replacement therapy.
    - Hereditary coagulation disorders.
    - Refusal to give consent for participation in the study.

    IN VIVO STUDY IN PATIENTS WITH UC

    PATIENTS WITH UC:
    - Under 18 years old.
    - Immune-mediated disease.
    - Neoplasm or active infection.
    - Pregnancy or lactation.
    - Alcohol or drug abuse.
    - Ostomy.
    - Abdominal surgery in the last 6 months.
    - Colectomy.
    - Active infection with hepatitis B, C or HIV virus.
    - Indication of anti-TNFα or JAK-inhibitors treatment for a cause other than UC.
    - Have previously received a drug with the same mechanism of action (anti-TNFα or JAK-inhibitors)
    - Medical history of thromboembolic events.
    -Treatment with anticoagulants, antiplatelets or other drugs that alter the coagulation.
    - Use of combined hormonal contraceptives or hormone replacement therapy.
    - Hereditary coagulation disorders.
    - Refusal to give consent for participation in the study.

    INDIVIDUALS WITHOUT UC:
    - Under 18 years of age.
    - Advanced chronic disease or any other pathology that prevents the monitoring
    of the protocol of this study.
    - Pregnancy or lactation.
    - Alcohol or drug abuse.
    - Active infection with hepatitis B, C or HIV virus.
    - Finding of macroscopic alterations during the colonoscopy or finding of relevant inflammatory alterations in the biopsies obtained during the colonoscopy.
    -Treatment with immunomodulators, immunosuppressants, corticosteroids or other drugs that alter the immune system.
    - Medical history of thromboembolic events.
    -Treatment with anticoagulants, antiplatelets or other drugs that alter the coagulation.
    - Use of combined hormonal contraceptives or hormone replacement therapy.
    - Hereditary coagulation disorders.
    - Refusal to give consent for participation in the study.
    ESTUDIO EX VIVO EN PACIENTES CON CU

    PACIENTES CON CU:

    - Menores de 18 años.
    - Padecer una enfermedad inmunomediada distinta de la CU en la visita basal.
    - Padecer una neoplasia o una infección activa en el momento de la visita basal.
    - Embarazo o lactancia.
    - Abuso de alcohol o drogas.
    - Ostomía.
    - Cirugía abdominal en los últimos 6 meses.
    - Colectomía.
    - Infección activa por virus de la hepatitis B, C o VIH.
    - Antecedentes médicos de eventos tromboembólicos.
    - Uso de fármacos anticoagulantes y antiagregantes.
    - Uso de anticonceptivos hormonales combinados o de terapia hormonal substitutiva.
    -Trastornos hereditarios de la coagulación.
    - Negativa a dar el consentimiento para la participación en el estudio.


    PACIENTES SIN CU:

    - Menores de 18 años.
    - Enfermedad crónica avanzada o cualquier otra patología que impida el seguimiento del protocolo de este estudio.
    - Embarazo o lactancia.
    - Abuso de alcohol o drogas.
    - Infección activa por virus de la hepatitis B, C o VIH.
    - Antecedentes médicos de eventos tromboembólicos.
    - Uso de fármacos anticoagulantes y antiagregantes.
    - Uso de anticonceptivos hormonales combinados o de terapia hormonal substitutiva.
    -Trastornos hereditarios de la coagulación.
    - Negativa a dar el consentimiento para la participación en el estudio.


    ESTUDIO IN VIVO EN PACIENTES CON CU

    PACIENTES CON CU:

    - Menores de 18 años.
    - Padecer una enfermedad inmunomediada distinta de la CU.
    - Padecer una neoplasia o una infección activa.
    - Embarazo o lactancia.
    - Abuso de alcohol o drogas.
    - Ostomía.
    - Cirugía abdominal en los últimos 6 meses.
    - Colectomía.
    - Infección activa por virus de la hepatitis B, C o VIH.
    - Indicación de tratamiento con anti-TNFα o inhibidores de JAK por una causa distinta a la CU.
    - Haber recibido previamente un fármaco con el mismo mecanismo de acción (anti-TNFα o inhibidores de JAK).
    - Antecedentes médicos de eventos tromboembólicos.
    - Uso de fármacos anticoagulantes y antiagregantes.
    - Uso de anticonceptivos hormonales combinados o de terapia hormonal substitutiva.
    -Trastornos hereditarios de la coagulación.
    - Negativa a dar el consentimiento para la participación en el estudio.

    PACIENTES SIN CU:

    - Menores de 18 años.
    - Enfermedad crónica avanzada o cualquier otra patología que impida el seguimiento del protocolo de este estudio.
    - Embarazo o lactancia.
    - Abuso de alcohol o drogas.
    - Infección activa por virus de la hepatitis B, C o VIH.
    - Hallazgo de alteraciones macroscópicas durante la realización de la colonoscopia, o hallazgo de alteraciones inflamatorias relevantes en las biopsias obtenidas durante la colonoscopia.
    - Tratamiento con inmunomoduladores, inmunosupresores, corticoides u otros fármacos que alteren el sistema inmune.
    - Antecedentes médicos de eventos tromboembólicos.
    - Uso de fármacos anticoagulantes y antiagregantes.
    - Uso de anticonceptivos hormonales combinados o de terapia hormonal substitutiva.
    - Trastornos hereditarios de la coagulación.
    - Negativa a dar el consentimiento para la participación en el estudio.
    E.5 End points
    E.5.1Primary end point(s)
    Study of platelet function [analysis of platelet activation (expression of surface markers PAC-1 and P-selectin) and platelet aggregation (percentage of maximum aggregation)] and clot formation kinetics using the ROTEM® technique [clotting time (seconds), clot formation time (seconds), angle α (degrees) and maximum clot strength (mm)] in peripheral blood samples from UC patients using an ex vivo approach (in the presence or absence of tofacitinib or anti-TNFα) and in vivo (in UC patients before and after initiation of tofacitinib or anti-TNFα treatment).
    Estudio de la función plaquetaria [análisis de activación plaquetaria (expresión de marcadores de superficie PAC-1 y P-selectina) y agregación plaquetaria (porcentaje de agregación máxima)] y cinética de formación del coágulo mediante la técnica ROTEM® [tiempo de coagulación (segundos), tiempo de formación del coágulo (segundos), ángulo α (grados) y fortaleza máxima del coágulo (mm)] en muestras de sangre periférica de pacientes con CU mediante un abordaje ex vivo (en presencia o ausencia de tofacitinib o anti-TNFα) e in vivo (en pacientes con CU antes y después de iniciar el tratamiento con tofacitinib o anti-TNFα).
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 months
    12 meses
    E.5.2Secondary end point(s)
    Determination of platelet activation:
    - Platelet activation status will be assessed ex vivo in platelet-rich plasma (PRP) samples from UC patients (active and quiescent) and healthy controls
    incubated in the absence or presence of drug (tofacitinib or anti-TNFα). Regarding the in vivo study, platelet activation will be analyzed in samples
    from patients with active UC before and after initiating treatment with tofacitinib or anti-TNFα.

    Platelet aggregation:
    - Platelet aggregation will be measured in PRP using a lumiaggregometer (Chrono-log Corporation, Havertown, PA, USA). In the case of the ex vivo
    study, PRP from UC patients (active and quiescent) and healthy controls will be incubated in the absence or presence of the different drugs (tofacitinib or anti-TNFα) and the results will be expressed as the percentage of maximum aggregation. Regarding the in vivo study, platelet aggregation will be
    analyzed in samples from patients with active UC before and after initiating treatment with tofacitinib or anti-TNFα.

    Clot formation study:
    - The procoagulant effect of tofacitinib in patients with UC will be evaluated ex vivo and in vivo using the rotational thromboelastometry technique
    (ROTEM®). For this purpose, the kinetics of clot formation will be studied using the INTEM test and the contribution of platelets to maximum clot
    firmness using the FIBTEM assay. For the ex vivo study, whole blood samples from UC patients (active and quiescent) and healthy controls
    incubated in the absence or presence of the different drugs (tofacitinib or anti-TNFα) will be incubated. As for the in vivo study, whole blood samples will be analyzed in patients with active UC before and after initiating treatment with tofacitinib or anti-TNFα.

    Endoscopic activity:
    - It will be evaluated by the Mayo endoscopic sub-score; endoscopic activity willbe considered as ≥ 2.

    Endoscopic response:
    - It will be defined as a decrease of ≥ 1 point in the Mayo endoscopic sub-score (62) 3 months after starting treatment.

    Endoscopic remission:
    - It will be defined as an endoscopic subscore ≤1, 3 months after starting treatment.

    Clinical activity:
    - It will be evaluated by the Partial Mayo Score. Clinical remission will be considered as a Partial Mayo Score ≤ 2, with all the scores (of the Partial
    Mayo Score) of 1 as a maximum and with a sub-score of rectal bleeding of 0, 3 months after starting treatment (63); and clinical response, the decrease of 3 or more points (of the Partial Mayo Score) with respect to the baseline situation (64).
    Determinación del estado de activación de las plaquetas:
    - El estado de activación plaquetaria se evaluará de manera ex vivo en muestras de plasma rico en plaquetas (PRP) de pacientes con CU (activa y quiescente) y controles sanos incubadas en ausencia o presencia de fármaco (tofacitinib o anti-TNFα). Respecto al estudio in vivo, la activación plaquetaria se analizará en las muestras de pacientes con CU activa antes y después de iniciar el tratamiento con tofacitinib o anti-TNFα.

    Estudio de la agregación plaquetaria:
    - La agregación plaquetaria se estudiará en PRP mediante un lumiagregómetro. En el caso del estudio ex vivo, se incubará el PRP de pacientes con CU (activa y quiescente) y controles sanos en ausencia o presencia de los distintos fármacos (tofacitinib o anti-TNFα) y los resultados se expresarán como el porcentaje de la agregación máxima. Respecto al estudio in vivo, la agregación plaquetaria se analizará en las muestras de pacientes con CU activa antes y después de iniciar el tratamiento con tofacitinib o anti-TNFα.

    Estudio de la formación del coágulo:
    - El efecto procoagulante de tofacitinib en pacientes con CU se evaluará mediante la técnica de tromboelastometría rotacional (ROTEM®) de manera ex vivo e in vivo. Para ello se estudiará la cinética de formación del coágulo mediante la prueba INTEM y la contribución de las plaquetas a la fortaleza máxima del coágulo mediante el ensayo FIBTEM. En el caso del estudio ex vivo, se incubarán las muestras de sangre completa de pacientes con CU (activa y quiescente) y controles sanos incubadas en ausencia o presencia de los distintos fármacos (tofacitinib o anti-TNFα). En cuanto al estudio in vivo, se analizarán las muestras de sangre completa en pacientes con CU activa antes y después de iniciar el tratamiento con tofacitinib o anti-TNFα.


    Actividad endoscópica:
    - En los pacientes con CU se evaluará mediante el subíndice endoscópico de Mayo (60,61); se considerará actividad endoscópica un subíndice endoscópico ≥2.

    Respuesta endoscópica (variable principal de valoración):
    - En los pacientes con CU, la respuesta endoscópica se definirá como una disminución ≥1 punto en el subíndice endoscópico de Mayo (62) 3 meses después de haber iniciado el tratamiento.

    Remisión endoscópica:
    - En los pacientes con CU, la remisión endoscópica se definirá como un subíndice endoscópico ≤1, 3 meses después de haber iniciado el tratamiento.

    Actividad clínica:
    - En los pacientes con CU se evaluará mediante el índice de Mayo parcial (63). Se considerará remisión clínica un índice de Mayo parcial ≤2, con todas las puntuaciones (del índice parcial) de 1 como máximo y con una subpuntuación de rectorragia de 0, 3 meses después de haber iniciado el tratamiento (63); y respuesta clínica, el descenso de 3 o más puntos (del índice de Mayo parcial) respecto a la situación basal (64).
    E.5.2.1Timepoint(s) of evaluation of this end point
    3 and 12 months
    3 y 12 meses
    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 No
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    healthy control
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    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: 50
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers Yes
    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 state60
    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)
    The treatment will be assigned by clinical practice and under the criteria of the researcher of each of the centers. Therefore, before starting the trial, as once it is over, it will be the responsible physician who decides in his clinical judgment which is the most appropriate therapeutic option.
    El tratamiento se asignará por práctica clínica y bajo el criterio del investigador de cada uno de los centros. Por lo tanto antes de iniciar el ensayo, como una vez finalizado será el médico responsable el que bajo su juicio clínico decida cual es la opción terapéutica más adecuada.
    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 Decision2021-08-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-07-22
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2023 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA