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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43861   clinical trials with a EudraCT protocol, of which   7284   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 on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:2018-000652-18
    Sponsor's Protocol Code Number:18IC4423
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2019-06-18
    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 ConcernedUK - MHRA
    A.2EudraCT number2018-000652-18
    A.3Full title of the trial
    Study to compare once-daily Extended Release Tacrolimus Versus twice-daily Immediate Release Tacrolimus following renal allograft failure to Reduce the risk of Allosensitisation
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to compare slow release (only required once day) versus fast release (needed to be taken twice a day) tacrolimus to reduce the risk of new antibodies forming against a failed transplant in patients on dialysis who are awaiting further transplantation
    A.3.2Name or abbreviated title of the trial where available
    EVITRA Study
    A.4.1Sponsor's protocol code number18IC4423
    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 SponsorImperial College London
    B.1.3.4Country
    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 supportChiesi Limited
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationImperial College London
    B.5.2Functional name of contact pointPereira Barreto
    B.5.3 Address:
    B.5.3.1Street AddressJoint Research Compliance Office
    B.5.3.2Town/ cityImperial College London
    B.5.3.3Post codeW2 1PG
    B.5.4Telephone number +44 020 7594 9480
    B.5.6E-mailg.pereira-barreto@imperial.ac.uk
    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 Yes
    D.2.1.1.1Trade name Envarsus
    D.2.1.1.2Name of the Marketing Authorisation holderChiesi Farmaceutici S.p.A.
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameEnvarsus
    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 INNtacrolimus
    D.3.9.1CAS number 109581-93-3
    D.3.9.4EV Substance CodeAS1
    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 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 Tacrolimus
    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 nameTacrolimus
    D.3.4Pharmaceutical form
    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 INNtacrolimus
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Transplant rejection following transplant failure and return to dialysis (transplant rejection defined as the development of new HLA antibodies against the transplant)
    E.1.1.1Medical condition in easily understood language
    Kidney transplant rejection in patients following failure of the transplant and return to dialysis
    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 LLT
    E.1.2Classification code 10050436
    E.1.2Term Prophylaxis against renal transplant rejection
    E.1.2System Organ Class 100000004865
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Does taking a preparation of a once-daily, slow release anti-rejection tablet (tacrolimus), compared with a twice-daily, immediate release anti-rejection tablet (tacrolimus) effect the incidence of new HLA antibodies (antibodies against another person's tissue/cells) in patients with failed kidney transplants who are on dialysis and are awaiting a further transplant.
    E.2.2Secondary objectives of the trial
    The hypothesis is that once-daily slow release tacrolimus may improve adherence and a higher proportion of 'target' drug (tacrolimus) blood levels than patients receiving immediate release tacrolimus. This in turn will be reflecting in the degree of new HLA antibodies detected in the participants.

    Adherence will be monitored using questionnaires in combination with drug (tacrolimus) levels. Quality of life measurements will also be assessed, to better assess the impact of return to dialysis in this population. The chances of re-transplantation will also be assessed using the data on new HLA antibody development in each group. This can be determined by using a calculator developed by NHS Blood and Transplant, who are responsible for transplant allocation.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Able to give informed consent.
    2. Male or female, at least 18 years of age.
    3. Has renal allograft failure and is due to start haemodialysis therapy, or within 28 days following starting dialysis.
    4. Has been already activated on the transplant wait list or is undergoing work up to be reactivated on the transplant live.
    5. Has no indication at the time of transplant failure for graft nephrectomy.
    6. Is receiving an immediate release tacrolimus maintenance immunotherapy regimen at the time of allograft failure.
    E.4Principal exclusion criteria
    1. Has another functioning organ transplanted (eg. pancreas, liver, cardiac) at the time of kidney allograft failure.
    2. Allograft failure within a month of transplantation.
    3. Patients who are due to receive or receiving peritoneal dialysis following graft failure.
    4. Patients with detectable DSA at the time of allograft failure
    5. Receiving an extended release preparation of tacrolimus as immunotherapy at the time of graft failure.
    6. Requires continuation of maintenance immunosuppression other than prednisolone or tacrolimus (eg. Mycophenolate mofetil or sirolimus).
    7. Patients who on IR-FK conversion would require less than 0.75mg of Envarsus.
    8. HLA type of donor unknown.
    9. Has a history of, or active co-morbidity that in the Investigator’s opinion, could affect the conduct of the study.
    10. Has any condition at the time of recruitment which would prohibit or pose a relative contraindication for the continued use of tacrolimus to a target trough level of between 3-5ng/ml
    11. Active bacterial, viral (including CMV and EBV) or parasitic infections, including tuberculosis that, in the Investigator’s opinion, could affect the conduct of the study.
    12. Has active malignancy.
    13. Female patients of child bearing age, who wish to consider pregnancy.
    E.5 End points
    E.5.1Primary end point(s)
    The rate of de novo HLA antibodies (or donor specific antibodies) developed at 24 months post recruitment.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary end point will be measured at 24 months post transplant failure.
    Routinely patients have their HLA antibodies measured every 3 months whilst on the transplant wait list.
    E.5.2Secondary end point(s)
    1. Adherence measurement (measured by a modified BAASIS questionnaire)
    2. QOL measurement (measured by the EQ-5D Health-Related Quality of Life Questionnaire)
    3. Coefficient of variation of tacrolimus levels at 24 months post allograft failure.
    4. Proportion of trough tacrolimus levels <3.0ng/ml.
    5. Incidence of infection episodes.
    6. Incidence of de novo malignancies.
    7. Rates of diabetes development (defined as the requirement of hypoglycaemic agents).
    8. Incidence of erythropoietin resistance (defined as failure to achieve or maintain haemoglobin levels within the desired target range despite appropriate ESA doses per kg of body weight).
    9. Requirement for clinically indicated allograft nephrectomy.
    10. Chances of re-transplantation as determined by the transplant matchability calculator available from NHSBT.
    11. Proportion of patients retransplanted during the study period.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The questionnaires will be performed at 3 months, 6 months and then 6 monthly intervals until the end of the trial at 2 years
    Tacrolimus levels will be monitored every 3 months
    Clinical assessments will be made every 3 months as part of routine care (de novo malignancies etc)
    The end of retransplantability will only be performed with the results of the final HLA antibody screen
    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 No
    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 Yes
    E.6.13.1Other scope of the trial description
    Observation/adherence
    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 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 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 concerned2
    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 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
    Last visit of the last subject is the end of the trial
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months11
    E.8.9.1In the Member State concerned days27
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months0
    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.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 60
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 8
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state64
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 64
    F.4.2.2In the whole clinical trial 64
    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)
    If patients in the extended release arm, are not transplanted and wish to continue with the extended release preparation, continuation will depend on local policy. At sites where other extended release tacrolimus is on formulary, patients may be required to switch brands if they wish to continue on the extended release preparation.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-07-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-07-27
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 25 21:54:54 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA