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   42567   clinical trials with a EudraCT protocol, of which   7008   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:2015-004572-30
    Sponsor's Protocol Code Number:GS-US-406-1840
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2016-02-12
    Trial results View 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 ConcernedUK - MHRA
    A.2EudraCT number2015-004572-30
    A.3Full title of the trial
    A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Tolerability of Entospletinib, a Selective SYK Inhibitor, in Combination with Systemic Corticosteroids as First-Line Therapy in Subjects with Chronic Graft Versus Host Disease (cGVHD)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study for Efficacy and Tolerability of Entospletinib in Combination with Corticosteroids as First-Line Therapy in (cGVHD)
    A.4.1Sponsor's protocol code numberGS-US-406-1840
    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 SponsorGilead Sciences, Inc.
    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 supportGilead Sciences, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGilead Sciences International Ltd.
    B.5.2Functional name of contact pointClinical Trials Mailbox
    B.5.3 Address:
    B.5.3.1Street AddressFlowers Building, Granta Park, Abington
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeCB21 6GT
    B.5.3.4CountryUnited Kingdom
    B.5.5Fax number+441223897284
    B.5.6E-mailclinical.trials@gilead.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.3.2Product code GS-9973
    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 INNEntospletinib
    D.3.9.3Other descriptive nameENTOSPLETINIB
    D.3.9.4EV Substance CodeSUB178740
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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.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
    Chronic Graft Versus Host Disease (cGVHD)
    E.1.1.1Medical condition in easily understood language
    Chronic Graft Versus Host Disease (cGVHD) is a disease observed in transplant recipients.
    E.1.1.2Therapeutic area Body processes [G] - Immune system processes [G12]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10066261
    E.1.2Term Chronic graft versus host disease
    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
    To evaluate the effect of ENTO on the best overall response rate (BORR) as assessed by the NIH cGVHD Activity Assessment (NCAA) by 24 weeks in the setting of add-on to systemic corticosteroids as part of first-line therapy for cGVHD
    E.2.2Secondary objectives of the trial
    The key secondary objectives are:
    - To evaluate the effect of ENTO on the skin domain of the Lee Symptom Scale (LSS) at 24 weeks
    - To evaluate the effect of ENTO on the mouth domain of the LSS at 24 weeks
    - To evaluate the effect of ENTO on the eyes domain of the LSS at 24 weeks
    - To evaluate the effect of ENTO on the total score of the LSS at 24 weeks
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1) The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
    2) 18-75 years of age, inclusive at Screening
    3) Newly diagnosed cGVHD defined by:
    a) At least 100 days after receiving any allogeneic hematopoietic stem cell transplant
    AND
    b) Receiving a new course of systemic corticosteroids (≥ 0.5 mg/kg/day) as first-line cGVHD therapy for at least 1 day
    and no more than 21 days prior to first dose of ENTO/Placebo
    AND
    c) Moderate to severe cGVHD as assessed by NCDSC with at least three organ systems involved OR one organ system with a score of 2 OR lung organ score = 1
    4) Subjects who have undergone transplantation for benign indications are eligible for the study. Complete remission is required for subjects who have undergone transplantations for hematologic malignancies.
    5) Have either a normal ECG or one with abnormalities that are considered clinically insignificant by the investigator in consultation with the Sponsor
    6) A negative serum pregnancy test is required for female subjects (unless permanently sterile or greater than two years post-menopausal)
    7) A female subject is eligible to enter the study if it is confirmed that she is:
    a) Not pregnant or nursing
    b) Of non-childbearing potential (i.e., women who have had a hysterectomy, have had both ovaries removed or medically documented ovarian failure, or are postmenopausal women > 54 years of age with cessation (for more than or equal to 12 months) of previously occurring menses), or
    c) Of childbearing potential and agrees to utilize a highly effective protocol-specified contraceptive method or be non-heterosexually active or practice sexual abstinence from Screening throughout the duration of study treatment and for 30 days following the last study drug dose
    d) Female subjects who utilize a hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
    8) Male subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception.
    9) Both female and male subjects of childbearing potential who are receiving mycophenolate mofetil (MMF) must agree to utilize contraceptive measures in accordance with the current MMF SmPC and the precautions for ENTO outlined in Appendix 8, whichever is stricter.
    E.4Principal exclusion criteria
    1) Inability to begin systemic corticosteroids therapy at a dose of ≥ 0.5 mg/kg/day (or equivalent)
    2) Uncontrolled infection within 4 weeks prior to Randomization
    3) History of the following therapies in the post-transplant period:
    a) B cell depleting biologic agents
    b) CD19 CAR-T cells based therapies
    c) BTK/SYK/JAK/PI3K inhibitors
    d) Phototherapy-unless administered for aGVHD
    4) Treatment of cGVHD with anti-thymocyte globulins (ATG), or campath within 60 days of Screening visit unless used for treatment of acute GVHD
    5) Severe organ dysfunction manifest during Screening period:
    a) Requiring supplemental oxygen at more than 2L/min
    b) Uncontrolled arrhythmia or heart failure
    c) Creatinine clearance (Cockroft-Gault) < 30 mL/min
    6) Known hypersensitivity to the Investigational Medicinal Product (IMP), the metabolites, or formulation excipient.
    7) Laboratory abnormalities including:
    a) Human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen or hepatitis C antibody positive (Subjects with positive HCV antibody and without detectable HCV RNA are permitted to enrol)
    b) Aspartate aminotrasferase (AST)/Alanine aminotransferase (ALT) ≥ 2 X upper limit of normal (ULN) unless deemed to be secondary to Liver GVHD
    c) Total bilirubin ≥ 2 X ULN unless deemed to be secondary to Liver GVHD
    8) Positive serum pregnancy test (for female subjects)
    9) Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements
    10) Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial
    11) Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance or subject safety
    12) Subjects receiving ongoing therapy with any of the medications from the following drug class: mTOR inhibitor, any cell depleting antibody, phototherapy, BTK agents, JAK inhibitors, strong and moderate CYP3A/2C9 inducers, strong CYP2C9 inhibitors, herbal/natural supplements
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is BORR as assessed by the NCAA by 24 weeks in the setting of add-on to systemic corticosteroids as part of first-line therapy for cGVHD
    E.5.1.1Timepoint(s) of evaluation of this end point
    24 weeks
    E.5.2Secondary end point(s)
    The key secondary endpoints are:
    - Change from Baseline in the skin domain of the LSS at 24 weeks
    - Change from Baseline in the mouth domain of the LSS at 24 weeks
    - Change from Baseline in the eyes domain of the LSS at 24 weeks
    - Change from Baseline in the total score of the LSS at 24 weeks
    E.5.2.1Timepoint(s) of evaluation of this end point
    24 weeks
    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 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) 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 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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA28
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    France
    Germany
    Korea, Republic of
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    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 months9
    E.8.9.1In the Member State concerned days28
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months10
    E.8.9.2In all countries concerned by the trial days27
    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: 95
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 5
    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 49
    F.4.2.2In the whole clinical trial 100
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    After the patient has completed/terminated their study participation, long term care of the participant will remain the responsibility of their primary treating physicians.
    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 Decision2016-03-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-03-10
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2017-12-14
    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 © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA